Emily A. Moore, PharmD, BCACP

More than 38 million people in the United States (12%) have diabetes mellitus (DM), though 1 in 5 are unaware they have DM.¹ The prevalence among veterans is even more substantial, impacting nearly 25% of those who received care from the US Department of Veterans Affairs (VA).² DM can lead to increased health care costs in addition to various complications (eg, cardiovascular, renal), especially if left uncontrolled.^1,3 similar impact is found in the perioperative period (defined as at or around the time of an operation), as multiple studies have found that uncontrolled preoperative DM can result in worsened surgical outcomes, including longer hospital stays, more infectious complications, and higher perioperative mortality.^4-6

In contrast, adequate glycemic control assessed with blood glucose levels has been shown to decrease the incidence of postoperative infections.⁷ Optimizing glycemic control during hospital stays, especially postsurgery, has become the standard of care, with most health systems establishing specific protocols. In current literature, most studies examining DM management in the perioperative period are focused on postoperative care, with little attention to the preoperative period.^4,6,7

One study found that patients with poor presurgery glycemic control assessed by hemoglobin A_1c (HbA_1c) levels were more likely to remain hyperglycemic during and after surgery. 8 Blood glucose levels < 200 mg/dL can lead to an increased risk of infection and impaired wound healing, meaning a well-controlled HbA_1c before a procedure serves as a potential factor for success.⁹ The 2025 American Diabetes Association (ADA) Standards of Care (SOC) recommendation is to target HbA_1c < 8% whenever possible, and some health systems require lower levels (eg, < 7% or 7.5%).¹⁰ With that goal in mind and knowing that preoperative hyperglycemia has been shown to be a contributing factor in the delay or cancellation of surgical cases, an argument can be made that attention to preoperative DM management also should be a focus for health care systems performing surgeries.^8,9,11

Attention to glucose control during preoperative care offers an opportunity to screen for DM in patients who may not have been screened otherwise and to standardize perioperative DM management. Since DM disproportionately impacts veterans, this is a pertinent issue to the VA. Veterans can be more susceptible to complications if DM is left uncontrolled prior to surgery. To determine readiness for surgery and control of comorbid conditions such as DM before a planned surgery, facilities often perform a preoperative clinic assessment, often in a multidisciplinary clinic.

At Veteran Health Indiana (VHI), a presurgery clinic visit involving the primary surgery service (physician, nurse practitioner, and/or a physician assistant) is conducted 1 to 2 months prior to the planned procedure to determine whether a patient is ready for surgery. During this visit, patients receive a packet with instructions for various tasks and medications, such as applying topical antibiotic prophylaxis on the anticipated surgical site. This is documented in the form of a note in the VHI Computerized Patient Record System (CPRS). The medication instructions are provided according to the preferences of the surgical team. These may be templated notes that contain general directions on the timing and dosing of specific medications, in addition to instructions for holding or reducing doses when appropriate. The instructions can be tailored by the team conducting the preoperative visit (eg, “Take 20 units of insulin glargine the day before surgery” vs “Take half of your long-acting insulin the night before surgery”). Specific to DM, VHI has a nurse-driven day of surgery glucose assessment where point-of-care blood glucose is collected during preoperative holding for most patients.

There is limited research assessing the level of preoperative glycemic control and the incidence of complications in a veteran population. The objective of this study was to gain a baseline understanding of what, if any, standardization exists for preoperative instructions for DM medications and to assess the level of preoperative glycemic control and postoperative complications in patients with DM undergoing major elective surgical procedures.

Methods

This retrospective, single-center chart review was conducted at VHI. The Indiana University and VHI institutional review boards determined that this quality improvement project was exempt from review.

The primary outcome was the number of patients with surgical procedures delayed or canceled due to hyperglycemia or hypoglycemia. Hyperglycemia was defined as blood glucose > 180 mg/dL and hypoglycemia was defined as < 70 mg/dL, slight variations from the current ADA SOC preoperative specific recommendation of a blood glucose reading of 100 to 180 mg/dL within 4 hours of surgery.¹⁰ The standard outpatient hypoglycemia definition of blood glucose < 70 mg/dL was chosen because the current goal (< 100 mg/dL) was not the standard in previous ADA SOCs that were in place during the study period. Specifically, the 2018 ADA SOC did not provide preoperative recommendations and the 2019-2021 ADA SOC recommended 80 to 180 mg/dL.^10,12-18 For patients who had multiple preoperative blood glucose measurements, the first recorded glucose on the day of the procedure was used.

The secondary outcomes of this study were focused on the preoperative process/care at VHI and postoperative glycemic control. The preoperative process included examining whether medication instructions were given and their quality. Additionally, the number of interventions for hyperglycemia and hypoglycemia were required immediately prior to surgery and the average preoperative HbA_1c (measured within 3 months prior to surgery) were collected and analyzed. For postoperative glycemic control, average blood glucose measurements and number of hypoglycemic (< 70 mg/dL) and hyperglycemic (> 180 mg/dL) events were measured in addition to the frequency of changes made at discharge to patients’ DM medication regimens.

The safety outcome of this study assessed commonly observed postoperative complications and was examined up to 30 days postsurgery. These included acute kidney injury (defined using Kidney Disease: Improving Global Outcomes 2012, the standard during the study period), nonfatal myocardial infarction, nonfatal stroke, and surgical site infections, which were identified from the discharge summary written by the primary surgery service.¹⁹ All-cause mortality also was collected.

Patients were included if they were admitted for major elective surgeries and had a diagnosis of either type 1 or type 2 DM on their problem list, determined by International Classification of Diseases, Tenth Revision codes. Major elective surgery was defined as a procedure that would likely result in a hospital admission of > 24 hours. Of note, patients may have been included in this study more than once if they had > 1 procedure at least 30 days apart and met inclusion criteria within the time frame. Patients were excluded if they were taking no DM medications or chronic steroids (at any dose), residing in a long-term care facility, being managed by a non-VA clinician prior to surgery, or missing a preoperative blood glucose measurement.

All data were collected from the CPRS. A list of surgical cases involving patients with DM who were scheduled to undergo major elective surgeries from January 1, 2018, to December 31, 2021, at VHI was generated. The list was randomized to a smaller number (N = 394) for data collection due to the time and resource constraints for a pharmacy residency project. All data were deidentified and stored in a secured VA server to protect patient confidentiality. Descriptive statistics were used for all results.

Results

Initially, 2362 surgeries were identified. A randomized sample of 394 charts were reviewed and 131 cases met inclusion criteria. Each case involved a unique patient (Figure). The most common reasons for exclusion were 143 patients with diet-controlled DM and 78 nonelective surgeries. The mean (SD) age of patients was 68 (8) years, and the most were male (98.5%) and White (76.3%) (Table 1). 

At baseline, 45 of 131 patients (34.4%) had coronary artery disease and 29 (22.1%) each had autonomic neuropathy and chronic kidney disease. Most surgeries were conducted by orthopedic (32.1%) and peripheral vascular (21.4%) specialties. The mean (SD) length of surgery was 4.6 (2.6) hours and of hospital length of stay was 4 (4) days. No patients stayed longer than the 30-day safety outcome follow-up period. All patients had type 2 DM and took a mean 2 DM medications. The 63 patients taking insulin had a mean (SD) total daily dose of 99 (77) U (Table 2). A preoperative HbA1c was collected in 116 patients within 3 months of surgery, with a mean HbA_1c of 7.0% (range, 5.3-10.7).

No patients had surgeries delayed or canceled because of uncontrolled DM on the day of surgery. The mean preoperative blood glucose level was 146 mg/dL (range, 73-365) (Table 3). No patients had a preoperative blood glucose level of < 70 mg/dL and 19 (14.5%) had a blood glucose level > 180 mg/dL. Among patients with hyperglycemia immediately prior to surgery, 6 (31.6%) had documentation of insulin being provided.

For this sample of patients, the preoperative clinic visit was conducted a mean 22 days prior to the planned surgery date. Among the 131 included patients, 122 (93.1%) had documentation of receiving instructions for DM medications. Among patients who had documented receipt of instructions, only 30 (24.6%) had instructions specifically tailored to their regimen rather than a generic templated form. The mean (SD) preoperative blood glucose was similar for those who received specific perioperative DM instructions at 146 (50) mg/dL when compared with those who did not at 147 (45) mg/dL. The mean (SD) preoperative blood glucose reading for those who had no documentation of receipt of perioperative instructions was 126 (54) mg/dL compared with 147 (46) mg/dL for those who did.

The mean number of postoperative blood glucose events per day was negligible for hypoglycemia and more frequent for hyperglycemia with a mean of 2 events per day. The mean postoperative blood glucose range was 121 to 247 mg/dL with most readings < 180 mg/dL. Upon discharge, most patients continued their home DM regimen with 5 patients (3.8%) having changes made to their regimen upon discharge.

Very few postoperative complications were identified from chart review. The most frequently observed postoperative complications were acute kidney injury, surgical site infections, and nonfatal stroke. There were no documented nonfatal myocardial infarctions. Two patients (1.5%) died within 30 days of the surgery; neither death was deemed to have been related to poor perioperative glycemic control.

Discussion

To our knowledge, this retrospective chart review was the first study to assess preoperative DM management and postoperative complications in a veteran population. VHI is a large, tertiary, level 1a, academic medical center that serves approximately 62,000 veterans annually and performs about 5000 to 6000 surgeries annually, a total that is increasing following the COVID-19 pandemic.²⁰ This study found that the current process of a presurgery clinic visit and day of surgery glucose assessment has prevented surgical delays or cancellations.

Most patients included in this study were well controlled at baseline in accordance with the 2025 ADA SOC HbA_1c recommendation of a preoperative HbA1c of < 8%, which may have contributed to no surgical delays or cancellations.¹⁰ However, not all patients had HbA1c collected within 3 months of surgery or even had one collected at all. Despite the ADA SOC providing no explicit recommendation for universal HbA_1c screening prior to elective procedures, its importance cannot be understated given the body of evidence demonstrating poor outcomes with uncontrolled preoperative DM.^8,10 The glycemic control at baseline may have contributed to the very few postsurgical complications observed in this study.

Although the current process at VHI prevented surgical delays and cancellations in this sample, there are still identified areas for improvement. One area is the instructions the patients received. Patients with DM are often prescribed ≥ 1 medication or a combination of insulins, noninsulin injectables, and oral DM medications, and this study population was no different. Because these medications may influence the anesthesia and perioperative periods, the ADA has specific guidance for altering administration schedules in the days leading up to surgery.¹⁰

Inappropriate administration of DM medications could lead to perioperative hypoglycemia or hyperglycemia, possibly causing surgical delays, case cancellations, and/or postoperative complications.21 Although these data reveal the specificity and documented receipt that the preoperative DM instructions did not impact the first recorded preoperative blood glucose, future studies should examine patient confidence in how to properly administer their DM medications prior to surgery. It is vital that patients receive clear instructions in accordance with the ADA SOC on whether to continue, hold, or adjust the dose of their medications to prevent fluctuations in blood glucose levels in the perioperative period, ensure safety with anesthesia, and prevent postoperative complications such as acute kidney injury. Of note, compliance with guideline recommendations for medication instructions was not examined because the data collection time frame expanded over multiple years and the recommendations have evolved each year as new data emerge.

Preoperative DM Management

The first key takeaway from this study is to ensure patients are ready for surgery with a formal assessment (typically in the form of a clinic visit) prior to the surgery. One private sector health system published their approach to this by administering an automatic preoperative HbA_1c screening for those with a DM diagnosis and all patients with a random plasma glucose ≥ 200 mg/dL.²² Additionally, if the patient's HbA_1c level was not at goal prior to surgery (≥ 8% for those with known DM and ≥ 6.5% with no known DM), patients were referred to endocrinology for further management. Increasing attention to the preoperative visit and extending HbA_1c testing to all patients regardless of DM status also provides an opportunity to identify individuals living with undiagnosed DM.¹

Even though there was no difference in the mean preoperative blood glucose level based on receipt or specificity of preoperative DM instructions, a second takeaway from this study is the importance of ensuring patients receive clear instructions on their DM medication schedule in the perioperative period. A practical first step may be updating the templates used by the primary surgery teams and providing education to the clinicians in the clinic on how to personalize the visits. Because the current preoperative DM process at VHI is managed by the primary surgical team in a clinic visit, there is an opportunity to shift this responsibility to other health care professionals, such as pharmacists—a change shown to reduce unintended omission of home medications following surgery during hospitalization and reduce costs.^23,24

Limitations

This study relied on data included in the patient chart. These data include medication interventions made immediately prior to surgery, which can sometimes be inaccurately charted or difficult to find as they are not documented in the typical medication administration record. Also, the safety outcomes were collected from a discharge summary written by different clinicians, which may lead to information bias. Special attention was taken to ensure these data points were collected as accurately as possible, but it is possible some data may be inaccurate from unintentional human error. Additionally, the safety outcome was limited to a 30-day follow-up, but encompassed the entire length of postoperative stay for all included patients. Finally, given this study was retrospective with no comparison group and the intent was to improve processes at VHI, only hypotheses and potential interventions can be generated from this study. Future prospective studies with larger sample sizes and comparator groups are needed to draw further conclusions.

Conclusions

This study found that the current presurgery process at VHI appears to be successful in preventing surgical delays or cancellations due to hyperglycemia or hypoglycemia. Optimizing DM management can improve surgical outcomes by decreasing rates of postoperative complications, and this study added additional evidence in support of that in a unique population: veterans. Insight on the awareness of preoperative blood glucose management should be gleaned from this study, and based on this sample and site, the preadmission screening process and instructions provided to patients can serve as 2 starting points for optimizing elective surgery.

More than 38 million people in the United States (12%) have diabetes mellitus (DM), though 1 in 5 are unaware they have DM.¹ The prevalence among veterans is even more substantial, impacting nearly 25% of those who received care from the US Department of Veterans Affairs (VA).² DM can lead to increased health care costs in addition to various complications (eg, cardiovascular, renal), especially if left uncontrolled.^1,3 similar impact is found in the perioperative period (defined as at or around the time of an operation), as multiple studies have found that uncontrolled preoperative DM can result in worsened surgical outcomes, including longer hospital stays, more infectious complications, and higher perioperative mortality.^4-6

In contrast, adequate glycemic control assessed with blood glucose levels has been shown to decrease the incidence of postoperative infections.⁷ Optimizing glycemic control during hospital stays, especially postsurgery, has become the standard of care, with most health systems establishing specific protocols. In current literature, most studies examining DM management in the perioperative period are focused on postoperative care, with little attention to the preoperative period.^4,6,7

One study found that patients with poor presurgery glycemic control assessed by hemoglobin A_1c (HbA_1c) levels were more likely to remain hyperglycemic during and after surgery. 8 Blood glucose levels < 200 mg/dL can lead to an increased risk of infection and impaired wound healing, meaning a well-controlled HbA_1c before a procedure serves as a potential factor for success.⁹ The 2025 American Diabetes Association (ADA) Standards of Care (SOC) recommendation is to target HbA_1c < 8% whenever possible, and some health systems require lower levels (eg, < 7% or 7.5%).¹⁰ With that goal in mind and knowing that preoperative hyperglycemia has been shown to be a contributing factor in the delay or cancellation of surgical cases, an argument can be made that attention to preoperative DM management also should be a focus for health care systems performing surgeries.^8,9,11

Attention to glucose control during preoperative care offers an opportunity to screen for DM in patients who may not have been screened otherwise and to standardize perioperative DM management. Since DM disproportionately impacts veterans, this is a pertinent issue to the VA. Veterans can be more susceptible to complications if DM is left uncontrolled prior to surgery. To determine readiness for surgery and control of comorbid conditions such as DM before a planned surgery, facilities often perform a preoperative clinic assessment, often in a multidisciplinary clinic.

At Veteran Health Indiana (VHI), a presurgery clinic visit involving the primary surgery service (physician, nurse practitioner, and/or a physician assistant) is conducted 1 to 2 months prior to the planned procedure to determine whether a patient is ready for surgery. During this visit, patients receive a packet with instructions for various tasks and medications, such as applying topical antibiotic prophylaxis on the anticipated surgical site. This is documented in the form of a note in the VHI Computerized Patient Record System (CPRS). The medication instructions are provided according to the preferences of the surgical team. These may be templated notes that contain general directions on the timing and dosing of specific medications, in addition to instructions for holding or reducing doses when appropriate. The instructions can be tailored by the team conducting the preoperative visit (eg, “Take 20 units of insulin glargine the day before surgery” vs “Take half of your long-acting insulin the night before surgery”). Specific to DM, VHI has a nurse-driven day of surgery glucose assessment where point-of-care blood glucose is collected during preoperative holding for most patients.

There is limited research assessing the level of preoperative glycemic control and the incidence of complications in a veteran population. The objective of this study was to gain a baseline understanding of what, if any, standardization exists for preoperative instructions for DM medications and to assess the level of preoperative glycemic control and postoperative complications in patients with DM undergoing major elective surgical procedures.

Methods

This retrospective, single-center chart review was conducted at VHI. The Indiana University and VHI institutional review boards determined that this quality improvement project was exempt from review.

The primary outcome was the number of patients with surgical procedures delayed or canceled due to hyperglycemia or hypoglycemia. Hyperglycemia was defined as blood glucose > 180 mg/dL and hypoglycemia was defined as < 70 mg/dL, slight variations from the current ADA SOC preoperative specific recommendation of a blood glucose reading of 100 to 180 mg/dL within 4 hours of surgery.¹⁰ The standard outpatient hypoglycemia definition of blood glucose < 70 mg/dL was chosen because the current goal (< 100 mg/dL) was not the standard in previous ADA SOCs that were in place during the study period. Specifically, the 2018 ADA SOC did not provide preoperative recommendations and the 2019-2021 ADA SOC recommended 80 to 180 mg/dL.^10,12-18 For patients who had multiple preoperative blood glucose measurements, the first recorded glucose on the day of the procedure was used.

The secondary outcomes of this study were focused on the preoperative process/care at VHI and postoperative glycemic control. The preoperative process included examining whether medication instructions were given and their quality. Additionally, the number of interventions for hyperglycemia and hypoglycemia were required immediately prior to surgery and the average preoperative HbA_1c (measured within 3 months prior to surgery) were collected and analyzed. For postoperative glycemic control, average blood glucose measurements and number of hypoglycemic (< 70 mg/dL) and hyperglycemic (> 180 mg/dL) events were measured in addition to the frequency of changes made at discharge to patients’ DM medication regimens.

The safety outcome of this study assessed commonly observed postoperative complications and was examined up to 30 days postsurgery. These included acute kidney injury (defined using Kidney Disease: Improving Global Outcomes 2012, the standard during the study period), nonfatal myocardial infarction, nonfatal stroke, and surgical site infections, which were identified from the discharge summary written by the primary surgery service.¹⁹ All-cause mortality also was collected.

Patients were included if they were admitted for major elective surgeries and had a diagnosis of either type 1 or type 2 DM on their problem list, determined by International Classification of Diseases, Tenth Revision codes. Major elective surgery was defined as a procedure that would likely result in a hospital admission of > 24 hours. Of note, patients may have been included in this study more than once if they had > 1 procedure at least 30 days apart and met inclusion criteria within the time frame. Patients were excluded if they were taking no DM medications or chronic steroids (at any dose), residing in a long-term care facility, being managed by a non-VA clinician prior to surgery, or missing a preoperative blood glucose measurement.

All data were collected from the CPRS. A list of surgical cases involving patients with DM who were scheduled to undergo major elective surgeries from January 1, 2018, to December 31, 2021, at VHI was generated. The list was randomized to a smaller number (N = 394) for data collection due to the time and resource constraints for a pharmacy residency project. All data were deidentified and stored in a secured VA server to protect patient confidentiality. Descriptive statistics were used for all results.

Results

Initially, 2362 surgeries were identified. A randomized sample of 394 charts were reviewed and 131 cases met inclusion criteria. Each case involved a unique patient (Figure). The most common reasons for exclusion were 143 patients with diet-controlled DM and 78 nonelective surgeries. The mean (SD) age of patients was 68 (8) years, and the most were male (98.5%) and White (76.3%) (Table 1). 

At baseline, 45 of 131 patients (34.4%) had coronary artery disease and 29 (22.1%) each had autonomic neuropathy and chronic kidney disease. Most surgeries were conducted by orthopedic (32.1%) and peripheral vascular (21.4%) specialties. The mean (SD) length of surgery was 4.6 (2.6) hours and of hospital length of stay was 4 (4) days. No patients stayed longer than the 30-day safety outcome follow-up period. All patients had type 2 DM and took a mean 2 DM medications. The 63 patients taking insulin had a mean (SD) total daily dose of 99 (77) U (Table 2). A preoperative HbA1c was collected in 116 patients within 3 months of surgery, with a mean HbA_1c of 7.0% (range, 5.3-10.7).

No patients had surgeries delayed or canceled because of uncontrolled DM on the day of surgery. The mean preoperative blood glucose level was 146 mg/dL (range, 73-365) (Table 3). No patients had a preoperative blood glucose level of < 70 mg/dL and 19 (14.5%) had a blood glucose level > 180 mg/dL. Among patients with hyperglycemia immediately prior to surgery, 6 (31.6%) had documentation of insulin being provided.

For this sample of patients, the preoperative clinic visit was conducted a mean 22 days prior to the planned surgery date. Among the 131 included patients, 122 (93.1%) had documentation of receiving instructions for DM medications. Among patients who had documented receipt of instructions, only 30 (24.6%) had instructions specifically tailored to their regimen rather than a generic templated form. The mean (SD) preoperative blood glucose was similar for those who received specific perioperative DM instructions at 146 (50) mg/dL when compared with those who did not at 147 (45) mg/dL. The mean (SD) preoperative blood glucose reading for those who had no documentation of receipt of perioperative instructions was 126 (54) mg/dL compared with 147 (46) mg/dL for those who did.

The mean number of postoperative blood glucose events per day was negligible for hypoglycemia and more frequent for hyperglycemia with a mean of 2 events per day. The mean postoperative blood glucose range was 121 to 247 mg/dL with most readings < 180 mg/dL. Upon discharge, most patients continued their home DM regimen with 5 patients (3.8%) having changes made to their regimen upon discharge.

Very few postoperative complications were identified from chart review. The most frequently observed postoperative complications were acute kidney injury, surgical site infections, and nonfatal stroke. There were no documented nonfatal myocardial infarctions. Two patients (1.5%) died within 30 days of the surgery; neither death was deemed to have been related to poor perioperative glycemic control.

Discussion

To our knowledge, this retrospective chart review was the first study to assess preoperative DM management and postoperative complications in a veteran population. VHI is a large, tertiary, level 1a, academic medical center that serves approximately 62,000 veterans annually and performs about 5000 to 6000 surgeries annually, a total that is increasing following the COVID-19 pandemic.²⁰ This study found that the current process of a presurgery clinic visit and day of surgery glucose assessment has prevented surgical delays or cancellations.

Most patients included in this study were well controlled at baseline in accordance with the 2025 ADA SOC HbA_1c recommendation of a preoperative HbA1c of < 8%, which may have contributed to no surgical delays or cancellations.¹⁰ However, not all patients had HbA1c collected within 3 months of surgery or even had one collected at all. Despite the ADA SOC providing no explicit recommendation for universal HbA_1c screening prior to elective procedures, its importance cannot be understated given the body of evidence demonstrating poor outcomes with uncontrolled preoperative DM.^8,10 The glycemic control at baseline may have contributed to the very few postsurgical complications observed in this study.

Although the current process at VHI prevented surgical delays and cancellations in this sample, there are still identified areas for improvement. One area is the instructions the patients received. Patients with DM are often prescribed ≥ 1 medication or a combination of insulins, noninsulin injectables, and oral DM medications, and this study population was no different. Because these medications may influence the anesthesia and perioperative periods, the ADA has specific guidance for altering administration schedules in the days leading up to surgery.¹⁰

Inappropriate administration of DM medications could lead to perioperative hypoglycemia or hyperglycemia, possibly causing surgical delays, case cancellations, and/or postoperative complications.21 Although these data reveal the specificity and documented receipt that the preoperative DM instructions did not impact the first recorded preoperative blood glucose, future studies should examine patient confidence in how to properly administer their DM medications prior to surgery. It is vital that patients receive clear instructions in accordance with the ADA SOC on whether to continue, hold, or adjust the dose of their medications to prevent fluctuations in blood glucose levels in the perioperative period, ensure safety with anesthesia, and prevent postoperative complications such as acute kidney injury. Of note, compliance with guideline recommendations for medication instructions was not examined because the data collection time frame expanded over multiple years and the recommendations have evolved each year as new data emerge.

Preoperative DM Management

The first key takeaway from this study is to ensure patients are ready for surgery with a formal assessment (typically in the form of a clinic visit) prior to the surgery. One private sector health system published their approach to this by administering an automatic preoperative HbA_1c screening for those with a DM diagnosis and all patients with a random plasma glucose ≥ 200 mg/dL.²² Additionally, if the patient's HbA_1c level was not at goal prior to surgery (≥ 8% for those with known DM and ≥ 6.5% with no known DM), patients were referred to endocrinology for further management. Increasing attention to the preoperative visit and extending HbA_1c testing to all patients regardless of DM status also provides an opportunity to identify individuals living with undiagnosed DM.¹

Even though there was no difference in the mean preoperative blood glucose level based on receipt or specificity of preoperative DM instructions, a second takeaway from this study is the importance of ensuring patients receive clear instructions on their DM medication schedule in the perioperative period. A practical first step may be updating the templates used by the primary surgery teams and providing education to the clinicians in the clinic on how to personalize the visits. Because the current preoperative DM process at VHI is managed by the primary surgical team in a clinic visit, there is an opportunity to shift this responsibility to other health care professionals, such as pharmacists—a change shown to reduce unintended omission of home medications following surgery during hospitalization and reduce costs.^23,24

Limitations

This study relied on data included in the patient chart. These data include medication interventions made immediately prior to surgery, which can sometimes be inaccurately charted or difficult to find as they are not documented in the typical medication administration record. Also, the safety outcomes were collected from a discharge summary written by different clinicians, which may lead to information bias. Special attention was taken to ensure these data points were collected as accurately as possible, but it is possible some data may be inaccurate from unintentional human error. Additionally, the safety outcome was limited to a 30-day follow-up, but encompassed the entire length of postoperative stay for all included patients. Finally, given this study was retrospective with no comparison group and the intent was to improve processes at VHI, only hypotheses and potential interventions can be generated from this study. Future prospective studies with larger sample sizes and comparator groups are needed to draw further conclusions.

Conclusions

This study found that the current presurgery process at VHI appears to be successful in preventing surgical delays or cancellations due to hyperglycemia or hypoglycemia. Optimizing DM management can improve surgical outcomes by decreasing rates of postoperative complications, and this study added additional evidence in support of that in a unique population: veterans. Insight on the awareness of preoperative blood glucose management should be gleaned from this study, and based on this sample and site, the preadmission screening process and instructions provided to patients can serve as 2 starting points for optimizing elective surgery.

More than 38 million people in the United States (12%) have diabetes mellitus (DM), though 1 in 5 are unaware they have DM.¹ The prevalence among veterans is even more substantial, impacting nearly 25% of those who received care from the US Department of Veterans Affairs (VA).² DM can lead to increased health care costs in addition to various complications (eg, cardiovascular, renal), especially if left uncontrolled.^1,3 similar impact is found in the perioperative period (defined as at or around the time of an operation), as multiple studies have found that uncontrolled preoperative DM can result in worsened surgical outcomes, including longer hospital stays, more infectious complications, and higher perioperative mortality.^4-6

In contrast, adequate glycemic control assessed with blood glucose levels has been shown to decrease the incidence of postoperative infections.⁷ Optimizing glycemic control during hospital stays, especially postsurgery, has become the standard of care, with most health systems establishing specific protocols. In current literature, most studies examining DM management in the perioperative period are focused on postoperative care, with little attention to the preoperative period.^4,6,7

One study found that patients with poor presurgery glycemic control assessed by hemoglobin A_1c (HbA_1c) levels were more likely to remain hyperglycemic during and after surgery. 8 Blood glucose levels < 200 mg/dL can lead to an increased risk of infection and impaired wound healing, meaning a well-controlled HbA_1c before a procedure serves as a potential factor for success.⁹ The 2025 American Diabetes Association (ADA) Standards of Care (SOC) recommendation is to target HbA_1c < 8% whenever possible, and some health systems require lower levels (eg, < 7% or 7.5%).¹⁰ With that goal in mind and knowing that preoperative hyperglycemia has been shown to be a contributing factor in the delay or cancellation of surgical cases, an argument can be made that attention to preoperative DM management also should be a focus for health care systems performing surgeries.^8,9,11

Attention to glucose control during preoperative care offers an opportunity to screen for DM in patients who may not have been screened otherwise and to standardize perioperative DM management. Since DM disproportionately impacts veterans, this is a pertinent issue to the VA. Veterans can be more susceptible to complications if DM is left uncontrolled prior to surgery. To determine readiness for surgery and control of comorbid conditions such as DM before a planned surgery, facilities often perform a preoperative clinic assessment, often in a multidisciplinary clinic.

At Veteran Health Indiana (VHI), a presurgery clinic visit involving the primary surgery service (physician, nurse practitioner, and/or a physician assistant) is conducted 1 to 2 months prior to the planned procedure to determine whether a patient is ready for surgery. During this visit, patients receive a packet with instructions for various tasks and medications, such as applying topical antibiotic prophylaxis on the anticipated surgical site. This is documented in the form of a note in the VHI Computerized Patient Record System (CPRS). The medication instructions are provided according to the preferences of the surgical team. These may be templated notes that contain general directions on the timing and dosing of specific medications, in addition to instructions for holding or reducing doses when appropriate. The instructions can be tailored by the team conducting the preoperative visit (eg, “Take 20 units of insulin glargine the day before surgery” vs “Take half of your long-acting insulin the night before surgery”). Specific to DM, VHI has a nurse-driven day of surgery glucose assessment where point-of-care blood glucose is collected during preoperative holding for most patients.

There is limited research assessing the level of preoperative glycemic control and the incidence of complications in a veteran population. The objective of this study was to gain a baseline understanding of what, if any, standardization exists for preoperative instructions for DM medications and to assess the level of preoperative glycemic control and postoperative complications in patients with DM undergoing major elective surgical procedures.

Methods

This retrospective, single-center chart review was conducted at VHI. The Indiana University and VHI institutional review boards determined that this quality improvement project was exempt from review.

The primary outcome was the number of patients with surgical procedures delayed or canceled due to hyperglycemia or hypoglycemia. Hyperglycemia was defined as blood glucose > 180 mg/dL and hypoglycemia was defined as < 70 mg/dL, slight variations from the current ADA SOC preoperative specific recommendation of a blood glucose reading of 100 to 180 mg/dL within 4 hours of surgery.¹⁰ The standard outpatient hypoglycemia definition of blood glucose < 70 mg/dL was chosen because the current goal (< 100 mg/dL) was not the standard in previous ADA SOCs that were in place during the study period. Specifically, the 2018 ADA SOC did not provide preoperative recommendations and the 2019-2021 ADA SOC recommended 80 to 180 mg/dL.^10,12-18 For patients who had multiple preoperative blood glucose measurements, the first recorded glucose on the day of the procedure was used.

The secondary outcomes of this study were focused on the preoperative process/care at VHI and postoperative glycemic control. The preoperative process included examining whether medication instructions were given and their quality. Additionally, the number of interventions for hyperglycemia and hypoglycemia were required immediately prior to surgery and the average preoperative HbA_1c (measured within 3 months prior to surgery) were collected and analyzed. For postoperative glycemic control, average blood glucose measurements and number of hypoglycemic (< 70 mg/dL) and hyperglycemic (> 180 mg/dL) events were measured in addition to the frequency of changes made at discharge to patients’ DM medication regimens.

The safety outcome of this study assessed commonly observed postoperative complications and was examined up to 30 days postsurgery. These included acute kidney injury (defined using Kidney Disease: Improving Global Outcomes 2012, the standard during the study period), nonfatal myocardial infarction, nonfatal stroke, and surgical site infections, which were identified from the discharge summary written by the primary surgery service.¹⁹ All-cause mortality also was collected.

Patients were included if they were admitted for major elective surgeries and had a diagnosis of either type 1 or type 2 DM on their problem list, determined by International Classification of Diseases, Tenth Revision codes. Major elective surgery was defined as a procedure that would likely result in a hospital admission of > 24 hours. Of note, patients may have been included in this study more than once if they had > 1 procedure at least 30 days apart and met inclusion criteria within the time frame. Patients were excluded if they were taking no DM medications or chronic steroids (at any dose), residing in a long-term care facility, being managed by a non-VA clinician prior to surgery, or missing a preoperative blood glucose measurement.

All data were collected from the CPRS. A list of surgical cases involving patients with DM who were scheduled to undergo major elective surgeries from January 1, 2018, to December 31, 2021, at VHI was generated. The list was randomized to a smaller number (N = 394) for data collection due to the time and resource constraints for a pharmacy residency project. All data were deidentified and stored in a secured VA server to protect patient confidentiality. Descriptive statistics were used for all results.

Results

Initially, 2362 surgeries were identified. A randomized sample of 394 charts were reviewed and 131 cases met inclusion criteria. Each case involved a unique patient (Figure). The most common reasons for exclusion were 143 patients with diet-controlled DM and 78 nonelective surgeries. The mean (SD) age of patients was 68 (8) years, and the most were male (98.5%) and White (76.3%) (Table 1). 

At baseline, 45 of 131 patients (34.4%) had coronary artery disease and 29 (22.1%) each had autonomic neuropathy and chronic kidney disease. Most surgeries were conducted by orthopedic (32.1%) and peripheral vascular (21.4%) specialties. The mean (SD) length of surgery was 4.6 (2.6) hours and of hospital length of stay was 4 (4) days. No patients stayed longer than the 30-day safety outcome follow-up period. All patients had type 2 DM and took a mean 2 DM medications. The 63 patients taking insulin had a mean (SD) total daily dose of 99 (77) U (Table 2). A preoperative HbA1c was collected in 116 patients within 3 months of surgery, with a mean HbA_1c of 7.0% (range, 5.3-10.7).

No patients had surgeries delayed or canceled because of uncontrolled DM on the day of surgery. The mean preoperative blood glucose level was 146 mg/dL (range, 73-365) (Table 3). No patients had a preoperative blood glucose level of < 70 mg/dL and 19 (14.5%) had a blood glucose level > 180 mg/dL. Among patients with hyperglycemia immediately prior to surgery, 6 (31.6%) had documentation of insulin being provided.

For this sample of patients, the preoperative clinic visit was conducted a mean 22 days prior to the planned surgery date. Among the 131 included patients, 122 (93.1%) had documentation of receiving instructions for DM medications. Among patients who had documented receipt of instructions, only 30 (24.6%) had instructions specifically tailored to their regimen rather than a generic templated form. The mean (SD) preoperative blood glucose was similar for those who received specific perioperative DM instructions at 146 (50) mg/dL when compared with those who did not at 147 (45) mg/dL. The mean (SD) preoperative blood glucose reading for those who had no documentation of receipt of perioperative instructions was 126 (54) mg/dL compared with 147 (46) mg/dL for those who did.

The mean number of postoperative blood glucose events per day was negligible for hypoglycemia and more frequent for hyperglycemia with a mean of 2 events per day. The mean postoperative blood glucose range was 121 to 247 mg/dL with most readings < 180 mg/dL. Upon discharge, most patients continued their home DM regimen with 5 patients (3.8%) having changes made to their regimen upon discharge.

Very few postoperative complications were identified from chart review. The most frequently observed postoperative complications were acute kidney injury, surgical site infections, and nonfatal stroke. There were no documented nonfatal myocardial infarctions. Two patients (1.5%) died within 30 days of the surgery; neither death was deemed to have been related to poor perioperative glycemic control.

Discussion

To our knowledge, this retrospective chart review was the first study to assess preoperative DM management and postoperative complications in a veteran population. VHI is a large, tertiary, level 1a, academic medical center that serves approximately 62,000 veterans annually and performs about 5000 to 6000 surgeries annually, a total that is increasing following the COVID-19 pandemic.²⁰ This study found that the current process of a presurgery clinic visit and day of surgery glucose assessment has prevented surgical delays or cancellations.

Most patients included in this study were well controlled at baseline in accordance with the 2025 ADA SOC HbA_1c recommendation of a preoperative HbA1c of < 8%, which may have contributed to no surgical delays or cancellations.¹⁰ However, not all patients had HbA1c collected within 3 months of surgery or even had one collected at all. Despite the ADA SOC providing no explicit recommendation for universal HbA_1c screening prior to elective procedures, its importance cannot be understated given the body of evidence demonstrating poor outcomes with uncontrolled preoperative DM.^8,10 The glycemic control at baseline may have contributed to the very few postsurgical complications observed in this study.

Although the current process at VHI prevented surgical delays and cancellations in this sample, there are still identified areas for improvement. One area is the instructions the patients received. Patients with DM are often prescribed ≥ 1 medication or a combination of insulins, noninsulin injectables, and oral DM medications, and this study population was no different. Because these medications may influence the anesthesia and perioperative periods, the ADA has specific guidance for altering administration schedules in the days leading up to surgery.¹⁰

Inappropriate administration of DM medications could lead to perioperative hypoglycemia or hyperglycemia, possibly causing surgical delays, case cancellations, and/or postoperative complications.21 Although these data reveal the specificity and documented receipt that the preoperative DM instructions did not impact the first recorded preoperative blood glucose, future studies should examine patient confidence in how to properly administer their DM medications prior to surgery. It is vital that patients receive clear instructions in accordance with the ADA SOC on whether to continue, hold, or adjust the dose of their medications to prevent fluctuations in blood glucose levels in the perioperative period, ensure safety with anesthesia, and prevent postoperative complications such as acute kidney injury. Of note, compliance with guideline recommendations for medication instructions was not examined because the data collection time frame expanded over multiple years and the recommendations have evolved each year as new data emerge.

Preoperative DM Management

The first key takeaway from this study is to ensure patients are ready for surgery with a formal assessment (typically in the form of a clinic visit) prior to the surgery. One private sector health system published their approach to this by administering an automatic preoperative HbA_1c screening for those with a DM diagnosis and all patients with a random plasma glucose ≥ 200 mg/dL.²² Additionally, if the patient's HbA_1c level was not at goal prior to surgery (≥ 8% for those with known DM and ≥ 6.5% with no known DM), patients were referred to endocrinology for further management. Increasing attention to the preoperative visit and extending HbA_1c testing to all patients regardless of DM status also provides an opportunity to identify individuals living with undiagnosed DM.¹

Even though there was no difference in the mean preoperative blood glucose level based on receipt or specificity of preoperative DM instructions, a second takeaway from this study is the importance of ensuring patients receive clear instructions on their DM medication schedule in the perioperative period. A practical first step may be updating the templates used by the primary surgery teams and providing education to the clinicians in the clinic on how to personalize the visits. Because the current preoperative DM process at VHI is managed by the primary surgical team in a clinic visit, there is an opportunity to shift this responsibility to other health care professionals, such as pharmacists—a change shown to reduce unintended omission of home medications following surgery during hospitalization and reduce costs.^23,24

Limitations

This study relied on data included in the patient chart. These data include medication interventions made immediately prior to surgery, which can sometimes be inaccurately charted or difficult to find as they are not documented in the typical medication administration record. Also, the safety outcomes were collected from a discharge summary written by different clinicians, which may lead to information bias. Special attention was taken to ensure these data points were collected as accurately as possible, but it is possible some data may be inaccurate from unintentional human error. Additionally, the safety outcome was limited to a 30-day follow-up, but encompassed the entire length of postoperative stay for all included patients. Finally, given this study was retrospective with no comparison group and the intent was to improve processes at VHI, only hypotheses and potential interventions can be generated from this study. Future prospective studies with larger sample sizes and comparator groups are needed to draw further conclusions.

Conclusions

This study found that the current presurgery process at VHI appears to be successful in preventing surgical delays or cancellations due to hyperglycemia or hypoglycemia. Optimizing DM management can improve surgical outcomes by decreasing rates of postoperative complications, and this study added additional evidence in support of that in a unique population: veterans. Insight on the awareness of preoperative blood glucose management should be gleaned from this study, and based on this sample and site, the preadmission screening process and instructions provided to patients can serve as 2 starting points for optimizing elective surgery.

The Centers for Disease Control and Prevention (CDC) classifies individuals with a body mass index (BMI) of 25 to 29.9as overweight and those with a BMI > 30 as obese (obesity classes: I, BMI 30 to 34.9; II, BMI 35 to 39.9; and III, BMI ≥ 40).¹ In 2011, the CDC estimated that 27.4% of adults in the United States were obese; less than a decade later, that number increased to 31.9%.¹ In that same period, the percentage of adults in Indiana classified as obese increased from 30.8% to 36.8%.¹ About 1 in 14 individuals in the US have class III obesity and 86% of veterans are either overweight or obese.²

High medical expenses can likely be attributed to the long-term health consequences of obesity. Compared to those with a healthy weight, individuals who are overweight or obese are at an increased risk for high blood pressure, high low-density lipoprotein cholesterol levels, low high-density lipoprotein cholesterol levels, high triglyceride levels, type 2 diabetes mellitus (T2DM), coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea, cancer, mental health disorders, body pain, low quality of life, and death.³ Many of these conditions lead to increased health care needs, medication needs, hospitalizations, and overall health care system use.

Guidelines for the prevention and treatment of obesity have been produced by the American Heart Association, American College of Cardiology, and The Obesity Society; the Endocrine Society; the American Diabetes Association; and the US Departments of Veterans Affairs (VA) and Defense. Each follows a general algorithm to manage and prevent adverse effects (AEs) related to obesity. General practice is to assess a patient for elevated BMI (> 25), implement intense lifestyle modifications including calorie restriction and exercise, reassess for a maintained 5% to 10% weight loss for cardiovascular benefits, and potentially assess for pharmacological or surgical intervention to assist in weight loss.^2,4-6

While some weight loss medications (eg, phentermine/topiramate, naltrexone/bupropion, orlistat, and lorcaserin) tend to have unfavorable AEs or mixed efficacy, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have provided new options.^7-10 Lorcaserin, for example, was removed from the market in 2020 due to its association with cancer risks.¹¹ The GLP-1RAs liraglutide and semaglutide received US Food and Drug Administration (FDA) approval for weight loss in 2014 and 2021, respectively.^12,13 GLP-1RAs have shown the greatest efficacy and benefits in reducing hemoglobin A_1c (HbA_1c); they are the preferred agents for patients who qualify for pharmacologic intervention for weight loss, especially those with T2DM. However, these studies have not evaluated the long-term outcomes of using these medications for weight loss and may not reflect the veteran population.^14,15

At Veteran Health Indiana (VHI), clinicians may use several weight loss medications for patients to achieve 5% to 10% weight loss. The medications most often used include liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone. However, more research is needed to determine which weight loss medication is the most beneficial for veterans, particularly following FDA approval of GLP-1RAs. At VHI, phentermine/topiramate is the preferred first-line agent unless patients have contraindications for use, in which case naltrexone/bupropion is recommended. These are considered first-line due to their ease of use in pill form, lower cost, and comparable weight loss to the GLP-1 medication class.² However, for patients with prediabetes, T2DM, BMI > 40, or BMI > 35 with specific comorbid conditions, liraglutide is preferred because of its beneficial effects for both weight loss and blood glucose control.²

This study aimed to expand on the 2021 Hood and colleagues study that examined total weight loss and weight loss as a percentage of baseline weight in patients with obesity at 3, 6, 12, and > 12 months of pharmacologic therapy by extending the time frame to 48 months.¹⁶ This study excluded semaglutide because few patients were prescribed the medication for weight loss during the study.

METHODS

We conducted a single-center, retrospective chart review of patients prescribed weight loss medications at VHI. A patient list was generated based on prescription fills from June 1, 2017, to July 31, 2021. Data were obtained from the Computerized Patient Record System; patients were not contacted. This study was approved by the Indiana University Health Institutional Review Board and VHI Research and Development Committee.

At the time of this study, liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone were available at VHI for patients who met the clinical criteria for use. All patients must have been enrolled in dietary and lifestyle management programs, including the VA MOVE! program, to be approved for these medications. After the MOVE! orientation, patients could participate in group or individual 12-week programs that included weigh-ins, goal-setting strategies, meal planning, and habit modification support. If patients could not meet in person, phone and other telehealth opportunities were available.

Patients were included in the study if they were aged ≥ 18 years, received a prescription for any of the 5 available medications for weight loss during the enrollment period, and were on the medication for ≥ 6 consecutive months. Patients were excluded if they received a prescription, were treated outside the VA system, or were pregnant. The primary indication for the included medication was not weight loss; the primary indication for the GLP-1RA was T2DM, or the weight loss was attributed to another disease. Adherence was not a measured outcome of this study; if patients were filling the medication, it was assumed they were taking it. Data were collected for each instance of medication use; as a result, a few patients were included more than once. Data collection for a failed medication ended when failure was documented. New data points began when new medication was prescribed; all data were per medication, not per patient. This allowed us to account for medication failure and provide accurate weight loss results based on medication choice within VHI.

Primary outcomes included total weight loss and weight loss as a percentage ofbaseline weight during the study period at 3, 6, 12, 24, 36, and 48 months of therapy. Secondary outcomes included the percentage of patients who lost 5% to 10% of their body weight from baseline; the percentage of patients who maintained ≥ 5% weight loss from baseline to 12, 24, 36, and 48 months if maintained on medication for that duration; duration of medication treatment in weeks; medication discontinuation rate; reason for medication discontinuation; enrollment in the MOVE! clinic and the time enrolled; percentage of patients with a BMI of 18 to 24.9 at the end of the study; and change in HbA_1c at 3, 6, 12, 24, 36, and 48 months.

Demographic data included race, age, sex, baseline weight, height, baseline BMI, and comorbid conditions (collected based on the most recent primary care clinical note before initiating medication). Medication data collected included medications used to manage comorbidities. Data related to weight management medication included prescribing clinic, maintenance dose of medication, duration of medication during the study period, the reason for medication discontinuation, or bariatric surgery intervention if applicable.

Basic descriptive statistics were used to characterize study participants. For continuous data, analysis of variance tests were used; if those results were not normal, then nonparametric tests were used, followed by pairwise tests between medication groups if the overall test was significant using the Fisher significant differences test. For nominal data, χ² or Fisher exact tests were used. For comparisons of primary and secondary outcomes, if the analyses needed to include adjustment for confounding variables, analysis of covariance was used for continuous data. A 2-sided 5% significance level was used for all tests.

RESULTS

A total of 228 instances of medication use were identified based on prescription fills; 123 did not meet inclusion criteria (117 for < 6 consecutive months of medication use) (Figure). The study included 105 participants with a mean age of 56 years; 80 were male (76.2%), and 85 identified as White race (81.0%). Mean (SD) weight was 130.1 kg (26.8) and BMI was 41.6 (7.2). The most common comorbid disease states among patients included hypertension, dyslipidemia, obstructive sleep apnea, and T2DM (Table 1). The baseline characteristics were comparable to those of Hood and colleagues.¹⁶

Most patients at VHI started on liraglutide (63%) or phentermine/topiramate (28%). For primary and secondary outcomes, statistics were calculated to determine whether the results were statistically significant for comparing the liraglutide and phentermine/topiramate subgroups. Sample sizes were too small for statistical analysis for bupropion/naltrexone, phentermine, and orlistat.

Primary Outcomes

The mean (SD) weight of participants dropped 8.1% from 130.1 kg to 119.5 kg over the patient-specific duration of weight management medication therapy for an absolute difference of 10.6 kg (9.7). Duration of individual medication use varied from 6 to 48 months. Weight loss was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. Patient weight was not recorded after the medication was discontinued.

When classified by medication choice, the mean change in weight over the duration of the study was −23.9 kg for 2 patients using orlistat, −10.2 kg for 46 patients using liraglutide, −11.0 kg for 25 patients using phentermine/topiramate, -7.4 kg for 1 patient using phentermine, and -13.0 kg for 4 patients using naltrexone/bupropion. Patients without a weight documented at the end of their therapy or at the conclusion of the data collection period were not included in the total weight loss at the end of therapy. There were 78 documented instances of weight loss at the end of therapy (Table 2).

Body weight loss percentage was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. The mean (SD) body weight loss percentage over the duration of the study was 9.2% (11.2). When classified by medication choice, the mean percentage of body weight loss was 16.8% for 2 patients using orlistat, 9.4% for 46 patients using liraglutide, 8.2% for 25 patients using phentermine/topiramate, 6.0% for 1 patient using phentermine alone, and 10.6% for 4 patients using naltrexone/bupropion (Table 3).

Secondary Outcomes

While none of the secondary outcomes were statistically significant, the results of this study suggest that both medications may contribute to weight loss in many patients included in this study. Almost two-thirds of the included patients analyzed lost ≥ 5% of weight from baseline while taking weight management medication. Sixty-six patients (63%) lost ≥ 5% of body weight at any time during the data collection period. When stratified by liraglutide and phentermine/topiramate, 41 patients (63%) taking liraglutide and 20 patients (67%) taking phentermine/topiramate lost ≥ 5% of weight from baseline. Of the 66 patients who lost ≥ 5% of body weight from baseline, 36 (55%) lost ≥ 10% of body weight from baseline at any time during the data collection period.

The mean (SD) duration for weight management medication use was 23 months (14.9). Phentermine/topiramate was tolerated longer than liraglutide: 22.7 months vs 21.7 months, respectively (Table 4).

The average overall documented medication discontinuation rate was 35.2%. Reasons for discontinuation included 21 patient-elected discontinuations, 8 patients no longer met criteria for use, 4 medications were no longer indicated, and 4 patients experienced AEs. It is unknown whether weight management medication was discontinued or not in 18 patients (17.2%).

This study evaluated the use and outcomes of weight loss medications over a longer period (up to 48 months) than what was previously studied among patients at VHI (12 months). The study aimed to better understand the long-term effect of weight loss medications, determine which medication had better long-term outcomes, and examine the reasons for medication discontinuation.

The results of this study displayed some similarities and differences compared with the Hood and colleagues study.¹⁶ Both yielded similar results for 5% of body weight loss and 10% of body weight loss. The largest difference was mean weight loss over the study period. In this study, patients lost a mean 10.6 kg over the course of weight loss medication use compared to 15.8 kg found by Hood and colleagues.¹⁶ A reason patients in the current study lost less weight overall could be the difference in time frames. The current study encompassed the COVID-19 pandemic, meaning fewer overall in-person patient appointments, which led to patients being lost to follow-up, missing weigh-ins during the time period, and gaps in care. For some patients, the pandemic possibly contributed to depression, missed medication doses, and a more sedentary lifestyle, leading to more weight gain.¹⁷ Telemedicine services at VHI expanded during the pandemic in an attempt to increase patient monitoring and counseling. It is unclear whether this expansion was enough to replace the in-person contact necessary to promote a healthy lifestyle.

VA pharmacists now care for patients through telehealth and are more involved in weight loss management. Since the conclusion of the Hood and colleagues study and start of this research, 2 pharmacists at VHI have been assigned to follow patients for obesity management to help with adherence to medication and lifestyle changes, management of AEs, dispense logistics, interventions for medications that may cause weight gain, and case management of glycemic control and weight loss with GLP-1RAs. Care management by pharmacists at VHI helps improve the logistics of titratable orders and save money by improving the use of high-cost items like GLP-1RAs. VA clinical pharmacy practitioners already monitor GLP-1RAs for patients with T2DM, so they are prepared to educate and assist patients with these medications.

It is important to continue developing a standardized process for weight loss medication management across the VA to improve the quality of patient care and optimize prescription outcomes. VA facilities differ in how weight loss management care is delivered and the level at which pharmacists are involved. Given the high rate of obesity among patients at the VA, the advent of new prescription options for weight loss, and the high cost associated with these medications, there has been increased attention to obesity care. Some Veterans Integrated Service Networks are forming a weight management community of practice groups to create standard operating procedures and algorithms to standardize care. Developing consistent processes is necessary to improve weight loss and patient care for veterans regardless where they receive treatment.

Limitations

The data used in this study were dependent on clinician documentation. Because of a lack of documentation in many instances, it was difficult to determine the full efficacy of the medications studied due to missing weight recordings. The lack of documentation made it difficult to determine whether patients were enrolled and active in the MOVE! program. It is required that patients enroll in MOVE! to obtain medications, but many did not have any follow-up MOVE! visits after initially obtaining their weight loss medication.

In this study, differences in the outcomes of patients with and without T2DM were not compared. It is the VA standard of care to prefer liraglutide over phentermine/topiramate in patients with T2DM or prediabetes.² This makes it difficult to assess whether phentermine/topiramate or liraglutide is more effective for weight loss in patients with T2DM. Weight gain after the discontinuation of weight loss medications was not assessed. Collecting this data may help determine whether a certain weight loss medication is less likely to cause rebound weight gain when discontinued.

Other limitations to this study consisted of excluding patients who discontinued therapy within 6 months, small sample sizes on some medications, and lack of data on adherence. Adherence was based on medication refills, which means that if a patient refilled the medication, it was assumed they were taking it. This is not always the case, and while accurate data on adherence is difficult to gather, it can impact how results may be interpreted. These additional limitations make it difficult to accurately determine the efficacy of the medications in this study.

CONCLUSIONS

This study found similar outcomes to what has been observed in larger clinical trials regarding weight loss medications. Nevertheless, there was a lack of accurate clinical documentation for most patients, which limits the conclusions. This lack of documentation potentially led to inaccurate results. It revealed that many patients at VHI did not uniformly receive consistent follow-up after starting a weight loss medication during the study period. With more standardized processes implemented at VA facilities, increased pharmacist involvement in weight loss medication management, and increased use of established telehealth services, patients could have the opportunity for closer follow-up that may lead to better weight loss outcomes. With these changes, there is more reason for additional studies to be conducted to assess follow-up, medication management, and weight loss overall.

The Centers for Disease Control and Prevention (CDC) classifies individuals with a body mass index (BMI) of 25 to 29.9as overweight and those with a BMI > 30 as obese (obesity classes: I, BMI 30 to 34.9; II, BMI 35 to 39.9; and III, BMI ≥ 40).¹ In 2011, the CDC estimated that 27.4% of adults in the United States were obese; less than a decade later, that number increased to 31.9%.¹ In that same period, the percentage of adults in Indiana classified as obese increased from 30.8% to 36.8%.¹ About 1 in 14 individuals in the US have class III obesity and 86% of veterans are either overweight or obese.²

High medical expenses can likely be attributed to the long-term health consequences of obesity. Compared to those with a healthy weight, individuals who are overweight or obese are at an increased risk for high blood pressure, high low-density lipoprotein cholesterol levels, low high-density lipoprotein cholesterol levels, high triglyceride levels, type 2 diabetes mellitus (T2DM), coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea, cancer, mental health disorders, body pain, low quality of life, and death.³ Many of these conditions lead to increased health care needs, medication needs, hospitalizations, and overall health care system use.

Guidelines for the prevention and treatment of obesity have been produced by the American Heart Association, American College of Cardiology, and The Obesity Society; the Endocrine Society; the American Diabetes Association; and the US Departments of Veterans Affairs (VA) and Defense. Each follows a general algorithm to manage and prevent adverse effects (AEs) related to obesity. General practice is to assess a patient for elevated BMI (> 25), implement intense lifestyle modifications including calorie restriction and exercise, reassess for a maintained 5% to 10% weight loss for cardiovascular benefits, and potentially assess for pharmacological or surgical intervention to assist in weight loss.^2,4-6

While some weight loss medications (eg, phentermine/topiramate, naltrexone/bupropion, orlistat, and lorcaserin) tend to have unfavorable AEs or mixed efficacy, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have provided new options.^7-10 Lorcaserin, for example, was removed from the market in 2020 due to its association with cancer risks.¹¹ The GLP-1RAs liraglutide and semaglutide received US Food and Drug Administration (FDA) approval for weight loss in 2014 and 2021, respectively.^12,13 GLP-1RAs have shown the greatest efficacy and benefits in reducing hemoglobin A_1c (HbA_1c); they are the preferred agents for patients who qualify for pharmacologic intervention for weight loss, especially those with T2DM. However, these studies have not evaluated the long-term outcomes of using these medications for weight loss and may not reflect the veteran population.^14,15

At Veteran Health Indiana (VHI), clinicians may use several weight loss medications for patients to achieve 5% to 10% weight loss. The medications most often used include liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone. However, more research is needed to determine which weight loss medication is the most beneficial for veterans, particularly following FDA approval of GLP-1RAs. At VHI, phentermine/topiramate is the preferred first-line agent unless patients have contraindications for use, in which case naltrexone/bupropion is recommended. These are considered first-line due to their ease of use in pill form, lower cost, and comparable weight loss to the GLP-1 medication class.² However, for patients with prediabetes, T2DM, BMI > 40, or BMI > 35 with specific comorbid conditions, liraglutide is preferred because of its beneficial effects for both weight loss and blood glucose control.²

This study aimed to expand on the 2021 Hood and colleagues study that examined total weight loss and weight loss as a percentage of baseline weight in patients with obesity at 3, 6, 12, and > 12 months of pharmacologic therapy by extending the time frame to 48 months.¹⁶ This study excluded semaglutide because few patients were prescribed the medication for weight loss during the study.

METHODS

We conducted a single-center, retrospective chart review of patients prescribed weight loss medications at VHI. A patient list was generated based on prescription fills from June 1, 2017, to July 31, 2021. Data were obtained from the Computerized Patient Record System; patients were not contacted. This study was approved by the Indiana University Health Institutional Review Board and VHI Research and Development Committee.

At the time of this study, liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone were available at VHI for patients who met the clinical criteria for use. All patients must have been enrolled in dietary and lifestyle management programs, including the VA MOVE! program, to be approved for these medications. After the MOVE! orientation, patients could participate in group or individual 12-week programs that included weigh-ins, goal-setting strategies, meal planning, and habit modification support. If patients could not meet in person, phone and other telehealth opportunities were available.

Patients were included in the study if they were aged ≥ 18 years, received a prescription for any of the 5 available medications for weight loss during the enrollment period, and were on the medication for ≥ 6 consecutive months. Patients were excluded if they received a prescription, were treated outside the VA system, or were pregnant. The primary indication for the included medication was not weight loss; the primary indication for the GLP-1RA was T2DM, or the weight loss was attributed to another disease. Adherence was not a measured outcome of this study; if patients were filling the medication, it was assumed they were taking it. Data were collected for each instance of medication use; as a result, a few patients were included more than once. Data collection for a failed medication ended when failure was documented. New data points began when new medication was prescribed; all data were per medication, not per patient. This allowed us to account for medication failure and provide accurate weight loss results based on medication choice within VHI.

Primary outcomes included total weight loss and weight loss as a percentage ofbaseline weight during the study period at 3, 6, 12, 24, 36, and 48 months of therapy. Secondary outcomes included the percentage of patients who lost 5% to 10% of their body weight from baseline; the percentage of patients who maintained ≥ 5% weight loss from baseline to 12, 24, 36, and 48 months if maintained on medication for that duration; duration of medication treatment in weeks; medication discontinuation rate; reason for medication discontinuation; enrollment in the MOVE! clinic and the time enrolled; percentage of patients with a BMI of 18 to 24.9 at the end of the study; and change in HbA_1c at 3, 6, 12, 24, 36, and 48 months.

Demographic data included race, age, sex, baseline weight, height, baseline BMI, and comorbid conditions (collected based on the most recent primary care clinical note before initiating medication). Medication data collected included medications used to manage comorbidities. Data related to weight management medication included prescribing clinic, maintenance dose of medication, duration of medication during the study period, the reason for medication discontinuation, or bariatric surgery intervention if applicable.

Basic descriptive statistics were used to characterize study participants. For continuous data, analysis of variance tests were used; if those results were not normal, then nonparametric tests were used, followed by pairwise tests between medication groups if the overall test was significant using the Fisher significant differences test. For nominal data, χ² or Fisher exact tests were used. For comparisons of primary and secondary outcomes, if the analyses needed to include adjustment for confounding variables, analysis of covariance was used for continuous data. A 2-sided 5% significance level was used for all tests.

RESULTS

A total of 228 instances of medication use were identified based on prescription fills; 123 did not meet inclusion criteria (117 for < 6 consecutive months of medication use) (Figure). The study included 105 participants with a mean age of 56 years; 80 were male (76.2%), and 85 identified as White race (81.0%). Mean (SD) weight was 130.1 kg (26.8) and BMI was 41.6 (7.2). The most common comorbid disease states among patients included hypertension, dyslipidemia, obstructive sleep apnea, and T2DM (Table 1). The baseline characteristics were comparable to those of Hood and colleagues.¹⁶

Most patients at VHI started on liraglutide (63%) or phentermine/topiramate (28%). For primary and secondary outcomes, statistics were calculated to determine whether the results were statistically significant for comparing the liraglutide and phentermine/topiramate subgroups. Sample sizes were too small for statistical analysis for bupropion/naltrexone, phentermine, and orlistat.

Primary Outcomes

The mean (SD) weight of participants dropped 8.1% from 130.1 kg to 119.5 kg over the patient-specific duration of weight management medication therapy for an absolute difference of 10.6 kg (9.7). Duration of individual medication use varied from 6 to 48 months. Weight loss was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. Patient weight was not recorded after the medication was discontinued.

When classified by medication choice, the mean change in weight over the duration of the study was −23.9 kg for 2 patients using orlistat, −10.2 kg for 46 patients using liraglutide, −11.0 kg for 25 patients using phentermine/topiramate, -7.4 kg for 1 patient using phentermine, and -13.0 kg for 4 patients using naltrexone/bupropion. Patients without a weight documented at the end of their therapy or at the conclusion of the data collection period were not included in the total weight loss at the end of therapy. There were 78 documented instances of weight loss at the end of therapy (Table 2).

Body weight loss percentage was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. The mean (SD) body weight loss percentage over the duration of the study was 9.2% (11.2). When classified by medication choice, the mean percentage of body weight loss was 16.8% for 2 patients using orlistat, 9.4% for 46 patients using liraglutide, 8.2% for 25 patients using phentermine/topiramate, 6.0% for 1 patient using phentermine alone, and 10.6% for 4 patients using naltrexone/bupropion (Table 3).

Secondary Outcomes

While none of the secondary outcomes were statistically significant, the results of this study suggest that both medications may contribute to weight loss in many patients included in this study. Almost two-thirds of the included patients analyzed lost ≥ 5% of weight from baseline while taking weight management medication. Sixty-six patients (63%) lost ≥ 5% of body weight at any time during the data collection period. When stratified by liraglutide and phentermine/topiramate, 41 patients (63%) taking liraglutide and 20 patients (67%) taking phentermine/topiramate lost ≥ 5% of weight from baseline. Of the 66 patients who lost ≥ 5% of body weight from baseline, 36 (55%) lost ≥ 10% of body weight from baseline at any time during the data collection period.

The mean (SD) duration for weight management medication use was 23 months (14.9). Phentermine/topiramate was tolerated longer than liraglutide: 22.7 months vs 21.7 months, respectively (Table 4).

The average overall documented medication discontinuation rate was 35.2%. Reasons for discontinuation included 21 patient-elected discontinuations, 8 patients no longer met criteria for use, 4 medications were no longer indicated, and 4 patients experienced AEs. It is unknown whether weight management medication was discontinued or not in 18 patients (17.2%).

This study evaluated the use and outcomes of weight loss medications over a longer period (up to 48 months) than what was previously studied among patients at VHI (12 months). The study aimed to better understand the long-term effect of weight loss medications, determine which medication had better long-term outcomes, and examine the reasons for medication discontinuation.

The results of this study displayed some similarities and differences compared with the Hood and colleagues study.¹⁶ Both yielded similar results for 5% of body weight loss and 10% of body weight loss. The largest difference was mean weight loss over the study period. In this study, patients lost a mean 10.6 kg over the course of weight loss medication use compared to 15.8 kg found by Hood and colleagues.¹⁶ A reason patients in the current study lost less weight overall could be the difference in time frames. The current study encompassed the COVID-19 pandemic, meaning fewer overall in-person patient appointments, which led to patients being lost to follow-up, missing weigh-ins during the time period, and gaps in care. For some patients, the pandemic possibly contributed to depression, missed medication doses, and a more sedentary lifestyle, leading to more weight gain.¹⁷ Telemedicine services at VHI expanded during the pandemic in an attempt to increase patient monitoring and counseling. It is unclear whether this expansion was enough to replace the in-person contact necessary to promote a healthy lifestyle.

VA pharmacists now care for patients through telehealth and are more involved in weight loss management. Since the conclusion of the Hood and colleagues study and start of this research, 2 pharmacists at VHI have been assigned to follow patients for obesity management to help with adherence to medication and lifestyle changes, management of AEs, dispense logistics, interventions for medications that may cause weight gain, and case management of glycemic control and weight loss with GLP-1RAs. Care management by pharmacists at VHI helps improve the logistics of titratable orders and save money by improving the use of high-cost items like GLP-1RAs. VA clinical pharmacy practitioners already monitor GLP-1RAs for patients with T2DM, so they are prepared to educate and assist patients with these medications.

It is important to continue developing a standardized process for weight loss medication management across the VA to improve the quality of patient care and optimize prescription outcomes. VA facilities differ in how weight loss management care is delivered and the level at which pharmacists are involved. Given the high rate of obesity among patients at the VA, the advent of new prescription options for weight loss, and the high cost associated with these medications, there has been increased attention to obesity care. Some Veterans Integrated Service Networks are forming a weight management community of practice groups to create standard operating procedures and algorithms to standardize care. Developing consistent processes is necessary to improve weight loss and patient care for veterans regardless where they receive treatment.

Limitations

The data used in this study were dependent on clinician documentation. Because of a lack of documentation in many instances, it was difficult to determine the full efficacy of the medications studied due to missing weight recordings. The lack of documentation made it difficult to determine whether patients were enrolled and active in the MOVE! program. It is required that patients enroll in MOVE! to obtain medications, but many did not have any follow-up MOVE! visits after initially obtaining their weight loss medication.

In this study, differences in the outcomes of patients with and without T2DM were not compared. It is the VA standard of care to prefer liraglutide over phentermine/topiramate in patients with T2DM or prediabetes.² This makes it difficult to assess whether phentermine/topiramate or liraglutide is more effective for weight loss in patients with T2DM. Weight gain after the discontinuation of weight loss medications was not assessed. Collecting this data may help determine whether a certain weight loss medication is less likely to cause rebound weight gain when discontinued.

Other limitations to this study consisted of excluding patients who discontinued therapy within 6 months, small sample sizes on some medications, and lack of data on adherence. Adherence was based on medication refills, which means that if a patient refilled the medication, it was assumed they were taking it. This is not always the case, and while accurate data on adherence is difficult to gather, it can impact how results may be interpreted. These additional limitations make it difficult to accurately determine the efficacy of the medications in this study.

CONCLUSIONS

This study found similar outcomes to what has been observed in larger clinical trials regarding weight loss medications. Nevertheless, there was a lack of accurate clinical documentation for most patients, which limits the conclusions. This lack of documentation potentially led to inaccurate results. It revealed that many patients at VHI did not uniformly receive consistent follow-up after starting a weight loss medication during the study period. With more standardized processes implemented at VA facilities, increased pharmacist involvement in weight loss medication management, and increased use of established telehealth services, patients could have the opportunity for closer follow-up that may lead to better weight loss outcomes. With these changes, there is more reason for additional studies to be conducted to assess follow-up, medication management, and weight loss overall.

The Centers for Disease Control and Prevention (CDC) classifies individuals with a body mass index (BMI) of 25 to 29.9as overweight and those with a BMI > 30 as obese (obesity classes: I, BMI 30 to 34.9; II, BMI 35 to 39.9; and III, BMI ≥ 40).¹ In 2011, the CDC estimated that 27.4% of adults in the United States were obese; less than a decade later, that number increased to 31.9%.¹ In that same period, the percentage of adults in Indiana classified as obese increased from 30.8% to 36.8%.¹ About 1 in 14 individuals in the US have class III obesity and 86% of veterans are either overweight or obese.²

High medical expenses can likely be attributed to the long-term health consequences of obesity. Compared to those with a healthy weight, individuals who are overweight or obese are at an increased risk for high blood pressure, high low-density lipoprotein cholesterol levels, low high-density lipoprotein cholesterol levels, high triglyceride levels, type 2 diabetes mellitus (T2DM), coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea, cancer, mental health disorders, body pain, low quality of life, and death.³ Many of these conditions lead to increased health care needs, medication needs, hospitalizations, and overall health care system use.

Guidelines for the prevention and treatment of obesity have been produced by the American Heart Association, American College of Cardiology, and The Obesity Society; the Endocrine Society; the American Diabetes Association; and the US Departments of Veterans Affairs (VA) and Defense. Each follows a general algorithm to manage and prevent adverse effects (AEs) related to obesity. General practice is to assess a patient for elevated BMI (> 25), implement intense lifestyle modifications including calorie restriction and exercise, reassess for a maintained 5% to 10% weight loss for cardiovascular benefits, and potentially assess for pharmacological or surgical intervention to assist in weight loss.^2,4-6

While some weight loss medications (eg, phentermine/topiramate, naltrexone/bupropion, orlistat, and lorcaserin) tend to have unfavorable AEs or mixed efficacy, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have provided new options.^7-10 Lorcaserin, for example, was removed from the market in 2020 due to its association with cancer risks.¹¹ The GLP-1RAs liraglutide and semaglutide received US Food and Drug Administration (FDA) approval for weight loss in 2014 and 2021, respectively.^12,13 GLP-1RAs have shown the greatest efficacy and benefits in reducing hemoglobin A_1c (HbA_1c); they are the preferred agents for patients who qualify for pharmacologic intervention for weight loss, especially those with T2DM. However, these studies have not evaluated the long-term outcomes of using these medications for weight loss and may not reflect the veteran population.^14,15

At Veteran Health Indiana (VHI), clinicians may use several weight loss medications for patients to achieve 5% to 10% weight loss. The medications most often used include liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone. However, more research is needed to determine which weight loss medication is the most beneficial for veterans, particularly following FDA approval of GLP-1RAs. At VHI, phentermine/topiramate is the preferred first-line agent unless patients have contraindications for use, in which case naltrexone/bupropion is recommended. These are considered first-line due to their ease of use in pill form, lower cost, and comparable weight loss to the GLP-1 medication class.² However, for patients with prediabetes, T2DM, BMI > 40, or BMI > 35 with specific comorbid conditions, liraglutide is preferred because of its beneficial effects for both weight loss and blood glucose control.²

This study aimed to expand on the 2021 Hood and colleagues study that examined total weight loss and weight loss as a percentage of baseline weight in patients with obesity at 3, 6, 12, and > 12 months of pharmacologic therapy by extending the time frame to 48 months.¹⁶ This study excluded semaglutide because few patients were prescribed the medication for weight loss during the study.

METHODS

We conducted a single-center, retrospective chart review of patients prescribed weight loss medications at VHI. A patient list was generated based on prescription fills from June 1, 2017, to July 31, 2021. Data were obtained from the Computerized Patient Record System; patients were not contacted. This study was approved by the Indiana University Health Institutional Review Board and VHI Research and Development Committee.

At the time of this study, liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone were available at VHI for patients who met the clinical criteria for use. All patients must have been enrolled in dietary and lifestyle management programs, including the VA MOVE! program, to be approved for these medications. After the MOVE! orientation, patients could participate in group or individual 12-week programs that included weigh-ins, goal-setting strategies, meal planning, and habit modification support. If patients could not meet in person, phone and other telehealth opportunities were available.

Patients were included in the study if they were aged ≥ 18 years, received a prescription for any of the 5 available medications for weight loss during the enrollment period, and were on the medication for ≥ 6 consecutive months. Patients were excluded if they received a prescription, were treated outside the VA system, or were pregnant. The primary indication for the included medication was not weight loss; the primary indication for the GLP-1RA was T2DM, or the weight loss was attributed to another disease. Adherence was not a measured outcome of this study; if patients were filling the medication, it was assumed they were taking it. Data were collected for each instance of medication use; as a result, a few patients were included more than once. Data collection for a failed medication ended when failure was documented. New data points began when new medication was prescribed; all data were per medication, not per patient. This allowed us to account for medication failure and provide accurate weight loss results based on medication choice within VHI.

Primary outcomes included total weight loss and weight loss as a percentage ofbaseline weight during the study period at 3, 6, 12, 24, 36, and 48 months of therapy. Secondary outcomes included the percentage of patients who lost 5% to 10% of their body weight from baseline; the percentage of patients who maintained ≥ 5% weight loss from baseline to 12, 24, 36, and 48 months if maintained on medication for that duration; duration of medication treatment in weeks; medication discontinuation rate; reason for medication discontinuation; enrollment in the MOVE! clinic and the time enrolled; percentage of patients with a BMI of 18 to 24.9 at the end of the study; and change in HbA_1c at 3, 6, 12, 24, 36, and 48 months.

Demographic data included race, age, sex, baseline weight, height, baseline BMI, and comorbid conditions (collected based on the most recent primary care clinical note before initiating medication). Medication data collected included medications used to manage comorbidities. Data related to weight management medication included prescribing clinic, maintenance dose of medication, duration of medication during the study period, the reason for medication discontinuation, or bariatric surgery intervention if applicable.

Basic descriptive statistics were used to characterize study participants. For continuous data, analysis of variance tests were used; if those results were not normal, then nonparametric tests were used, followed by pairwise tests between medication groups if the overall test was significant using the Fisher significant differences test. For nominal data, χ² or Fisher exact tests were used. For comparisons of primary and secondary outcomes, if the analyses needed to include adjustment for confounding variables, analysis of covariance was used for continuous data. A 2-sided 5% significance level was used for all tests.

RESULTS

A total of 228 instances of medication use were identified based on prescription fills; 123 did not meet inclusion criteria (117 for < 6 consecutive months of medication use) (Figure). The study included 105 participants with a mean age of 56 years; 80 were male (76.2%), and 85 identified as White race (81.0%). Mean (SD) weight was 130.1 kg (26.8) and BMI was 41.6 (7.2). The most common comorbid disease states among patients included hypertension, dyslipidemia, obstructive sleep apnea, and T2DM (Table 1). The baseline characteristics were comparable to those of Hood and colleagues.¹⁶

Most patients at VHI started on liraglutide (63%) or phentermine/topiramate (28%). For primary and secondary outcomes, statistics were calculated to determine whether the results were statistically significant for comparing the liraglutide and phentermine/topiramate subgroups. Sample sizes were too small for statistical analysis for bupropion/naltrexone, phentermine, and orlistat.

Primary Outcomes

The mean (SD) weight of participants dropped 8.1% from 130.1 kg to 119.5 kg over the patient-specific duration of weight management medication therapy for an absolute difference of 10.6 kg (9.7). Duration of individual medication use varied from 6 to 48 months. Weight loss was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. Patient weight was not recorded after the medication was discontinued.

When classified by medication choice, the mean change in weight over the duration of the study was −23.9 kg for 2 patients using orlistat, −10.2 kg for 46 patients using liraglutide, −11.0 kg for 25 patients using phentermine/topiramate, -7.4 kg for 1 patient using phentermine, and -13.0 kg for 4 patients using naltrexone/bupropion. Patients without a weight documented at the end of their therapy or at the conclusion of the data collection period were not included in the total weight loss at the end of therapy. There were 78 documented instances of weight loss at the end of therapy (Table 2).

Body weight loss percentage was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. The mean (SD) body weight loss percentage over the duration of the study was 9.2% (11.2). When classified by medication choice, the mean percentage of body weight loss was 16.8% for 2 patients using orlistat, 9.4% for 46 patients using liraglutide, 8.2% for 25 patients using phentermine/topiramate, 6.0% for 1 patient using phentermine alone, and 10.6% for 4 patients using naltrexone/bupropion (Table 3).

Secondary Outcomes

While none of the secondary outcomes were statistically significant, the results of this study suggest that both medications may contribute to weight loss in many patients included in this study. Almost two-thirds of the included patients analyzed lost ≥ 5% of weight from baseline while taking weight management medication. Sixty-six patients (63%) lost ≥ 5% of body weight at any time during the data collection period. When stratified by liraglutide and phentermine/topiramate, 41 patients (63%) taking liraglutide and 20 patients (67%) taking phentermine/topiramate lost ≥ 5% of weight from baseline. Of the 66 patients who lost ≥ 5% of body weight from baseline, 36 (55%) lost ≥ 10% of body weight from baseline at any time during the data collection period.

The mean (SD) duration for weight management medication use was 23 months (14.9). Phentermine/topiramate was tolerated longer than liraglutide: 22.7 months vs 21.7 months, respectively (Table 4).

The average overall documented medication discontinuation rate was 35.2%. Reasons for discontinuation included 21 patient-elected discontinuations, 8 patients no longer met criteria for use, 4 medications were no longer indicated, and 4 patients experienced AEs. It is unknown whether weight management medication was discontinued or not in 18 patients (17.2%).

This study evaluated the use and outcomes of weight loss medications over a longer period (up to 48 months) than what was previously studied among patients at VHI (12 months). The study aimed to better understand the long-term effect of weight loss medications, determine which medication had better long-term outcomes, and examine the reasons for medication discontinuation.

The results of this study displayed some similarities and differences compared with the Hood and colleagues study.¹⁶ Both yielded similar results for 5% of body weight loss and 10% of body weight loss. The largest difference was mean weight loss over the study period. In this study, patients lost a mean 10.6 kg over the course of weight loss medication use compared to 15.8 kg found by Hood and colleagues.¹⁶ A reason patients in the current study lost less weight overall could be the difference in time frames. The current study encompassed the COVID-19 pandemic, meaning fewer overall in-person patient appointments, which led to patients being lost to follow-up, missing weigh-ins during the time period, and gaps in care. For some patients, the pandemic possibly contributed to depression, missed medication doses, and a more sedentary lifestyle, leading to more weight gain.¹⁷ Telemedicine services at VHI expanded during the pandemic in an attempt to increase patient monitoring and counseling. It is unclear whether this expansion was enough to replace the in-person contact necessary to promote a healthy lifestyle.

VA pharmacists now care for patients through telehealth and are more involved in weight loss management. Since the conclusion of the Hood and colleagues study and start of this research, 2 pharmacists at VHI have been assigned to follow patients for obesity management to help with adherence to medication and lifestyle changes, management of AEs, dispense logistics, interventions for medications that may cause weight gain, and case management of glycemic control and weight loss with GLP-1RAs. Care management by pharmacists at VHI helps improve the logistics of titratable orders and save money by improving the use of high-cost items like GLP-1RAs. VA clinical pharmacy practitioners already monitor GLP-1RAs for patients with T2DM, so they are prepared to educate and assist patients with these medications.

It is important to continue developing a standardized process for weight loss medication management across the VA to improve the quality of patient care and optimize prescription outcomes. VA facilities differ in how weight loss management care is delivered and the level at which pharmacists are involved. Given the high rate of obesity among patients at the VA, the advent of new prescription options for weight loss, and the high cost associated with these medications, there has been increased attention to obesity care. Some Veterans Integrated Service Networks are forming a weight management community of practice groups to create standard operating procedures and algorithms to standardize care. Developing consistent processes is necessary to improve weight loss and patient care for veterans regardless where they receive treatment.

Limitations

The data used in this study were dependent on clinician documentation. Because of a lack of documentation in many instances, it was difficult to determine the full efficacy of the medications studied due to missing weight recordings. The lack of documentation made it difficult to determine whether patients were enrolled and active in the MOVE! program. It is required that patients enroll in MOVE! to obtain medications, but many did not have any follow-up MOVE! visits after initially obtaining their weight loss medication.

In this study, differences in the outcomes of patients with and without T2DM were not compared. It is the VA standard of care to prefer liraglutide over phentermine/topiramate in patients with T2DM or prediabetes.² This makes it difficult to assess whether phentermine/topiramate or liraglutide is more effective for weight loss in patients with T2DM. Weight gain after the discontinuation of weight loss medications was not assessed. Collecting this data may help determine whether a certain weight loss medication is less likely to cause rebound weight gain when discontinued.

Other limitations to this study consisted of excluding patients who discontinued therapy within 6 months, small sample sizes on some medications, and lack of data on adherence. Adherence was based on medication refills, which means that if a patient refilled the medication, it was assumed they were taking it. This is not always the case, and while accurate data on adherence is difficult to gather, it can impact how results may be interpreted. These additional limitations make it difficult to accurately determine the efficacy of the medications in this study.

CONCLUSIONS

This study found similar outcomes to what has been observed in larger clinical trials regarding weight loss medications. Nevertheless, there was a lack of accurate clinical documentation for most patients, which limits the conclusions. This lack of documentation potentially led to inaccurate results. It revealed that many patients at VHI did not uniformly receive consistent follow-up after starting a weight loss medication during the study period. With more standardized processes implemented at VA facilities, increased pharmacist involvement in weight loss medication management, and increased use of established telehealth services, patients could have the opportunity for closer follow-up that may lead to better weight loss outcomes. With these changes, there is more reason for additional studies to be conducted to assess follow-up, medication management, and weight loss overall.