Diabetes

Key clinical point: Combination of saxagliptin with metformin, acarbose, or gliclazide modified release was safe and effective as an initial treatment option in patients with newly diagnosed type 2 diabetes (T2D) and poor glycemic control.

Major finding: At 24 weeks, the mean changes in glycated hemoglobin (A1c) levels were −2.9% (95% CI −3.1% to −2.8%), −2.6% (95% CI −2.8% to −2.5%), and −2.8% (95% CI −2.9% to −2.6%) in saxagliptin+metformin (Saxa+Met), saxagliptin+acarbose (Saxa+Aca), and saxagliptin+gliclazide (Saxa+Gli) groups, respectively. Overall, 84.9%, 74.7%, and 80.3% of participants achieved an A1c < 7.0% in Saxa+Met, Saxa+Aca, and Saxa+Gli groups, respectively (P = .05), with the rates of hypoglycemia being low across all groups.

Study details: Findings are from a 24-week, randomized clinical trial including 648 treatment-naive patients with T2D and high A1c level who were randomly assigned to receive Saxa+Met (n = 216), Saxa+Aca (n = 216), or Saxa+Gli (n = 216).

Disclosures: This study was funded by AstraZeneca Pharmaceutical Company. The authors declared no conflicts of interest.

Source: Chen X et al. Saxagliptin combined with additional oral antihyperglycemic agents in drug-naive diabetic patients with high glycosylated hemoglobin: A 24-week, multicenter, randomized, open-label, active parallel-controlled group clinical trial in China (SUCCESS). Diabetes Obes Metab. 2022 (Sep 13). Doi: 10.1111/dom.14873

Key clinical point: Combination of saxagliptin with metformin, acarbose, or gliclazide modified release was safe and effective as an initial treatment option in patients with newly diagnosed type 2 diabetes (T2D) and poor glycemic control.

Major finding: At 24 weeks, the mean changes in glycated hemoglobin (A1c) levels were −2.9% (95% CI −3.1% to −2.8%), −2.6% (95% CI −2.8% to −2.5%), and −2.8% (95% CI −2.9% to −2.6%) in saxagliptin+metformin (Saxa+Met), saxagliptin+acarbose (Saxa+Aca), and saxagliptin+gliclazide (Saxa+Gli) groups, respectively. Overall, 84.9%, 74.7%, and 80.3% of participants achieved an A1c < 7.0% in Saxa+Met, Saxa+Aca, and Saxa+Gli groups, respectively (P = .05), with the rates of hypoglycemia being low across all groups.

Study details: Findings are from a 24-week, randomized clinical trial including 648 treatment-naive patients with T2D and high A1c level who were randomly assigned to receive Saxa+Met (n = 216), Saxa+Aca (n = 216), or Saxa+Gli (n = 216).

Disclosures: This study was funded by AstraZeneca Pharmaceutical Company. The authors declared no conflicts of interest.

Source: Chen X et al. Saxagliptin combined with additional oral antihyperglycemic agents in drug-naive diabetic patients with high glycosylated hemoglobin: A 24-week, multicenter, randomized, open-label, active parallel-controlled group clinical trial in China (SUCCESS). Diabetes Obes Metab. 2022 (Sep 13). Doi: 10.1111/dom.14873

Key clinical point: Combination of saxagliptin with metformin, acarbose, or gliclazide modified release was safe and effective as an initial treatment option in patients with newly diagnosed type 2 diabetes (T2D) and poor glycemic control.

Major finding: At 24 weeks, the mean changes in glycated hemoglobin (A1c) levels were −2.9% (95% CI −3.1% to −2.8%), −2.6% (95% CI −2.8% to −2.5%), and −2.8% (95% CI −2.9% to −2.6%) in saxagliptin+metformin (Saxa+Met), saxagliptin+acarbose (Saxa+Aca), and saxagliptin+gliclazide (Saxa+Gli) groups, respectively. Overall, 84.9%, 74.7%, and 80.3% of participants achieved an A1c < 7.0% in Saxa+Met, Saxa+Aca, and Saxa+Gli groups, respectively (P = .05), with the rates of hypoglycemia being low across all groups.

Study details: Findings are from a 24-week, randomized clinical trial including 648 treatment-naive patients with T2D and high A1c level who were randomly assigned to receive Saxa+Met (n = 216), Saxa+Aca (n = 216), or Saxa+Gli (n = 216).

Disclosures: This study was funded by AstraZeneca Pharmaceutical Company. The authors declared no conflicts of interest.

Source: Chen X et al. Saxagliptin combined with additional oral antihyperglycemic agents in drug-naive diabetic patients with high glycosylated hemoglobin: A 24-week, multicenter, randomized, open-label, active parallel-controlled group clinical trial in China (SUCCESS). Diabetes Obes Metab. 2022 (Sep 13). Doi: 10.1111/dom.14873

Key clinical point: As an adjunct to metformin, bexagliflozin (20 mg) demonstrated antidiabetic potency equivalent to titrated glimepiride in patients with type 2 diabetes (T2D) inadequately controlled on metformin. Additional benefits were demonstrated in the form of weight loss, reduced systolic blood pressure (SBP), and fewer hypoglycemic events.

Major finding: At week 60, the least squares mean difference in glycated hemoglobin levels between bexagliflozin and glimepiride was −0.05% (95% CI −0.21% to 0.11%), showing noninferiority of bexagliflozin over glimepiride; however, bexagliflozin was superior to glimepiride for weight loss (P < .0001), decrease in SBP (P = .0008), and hypoglycemia incidence (P < .0001).

Study details: This 96-week randomized controlled trial included 426 patients with T2D (7.0% ≤ A1c ≤ 10.5%) inadequately controlled on metformin who were randomly assigned to receive bexagliflozin (n = 213) or titrated glimepiride (n = 213).

Disclosures: This study was funded by Theracos Sub, LLC. Some authors including the lead author were supported by a research grant to the Massachusetts General Hospital from Theracos Sub, LLC.

Source: Halvorsen YD et al. A 96-week, double-blind, randomized, controlled trial comparing bexagliflozin to glimepiride as an adjunct to metformin for the treatment of type 2 diabetes in adults. Diabetes Obes Metab. 2022 (Sep 30). Doi: 10.1111/dom.14875

Key clinical point: As an adjunct to metformin, bexagliflozin (20 mg) demonstrated antidiabetic potency equivalent to titrated glimepiride in patients with type 2 diabetes (T2D) inadequately controlled on metformin. Additional benefits were demonstrated in the form of weight loss, reduced systolic blood pressure (SBP), and fewer hypoglycemic events.

Major finding: At week 60, the least squares mean difference in glycated hemoglobin levels between bexagliflozin and glimepiride was −0.05% (95% CI −0.21% to 0.11%), showing noninferiority of bexagliflozin over glimepiride; however, bexagliflozin was superior to glimepiride for weight loss (P < .0001), decrease in SBP (P = .0008), and hypoglycemia incidence (P < .0001).

Study details: This 96-week randomized controlled trial included 426 patients with T2D (7.0% ≤ A1c ≤ 10.5%) inadequately controlled on metformin who were randomly assigned to receive bexagliflozin (n = 213) or titrated glimepiride (n = 213).

Disclosures: This study was funded by Theracos Sub, LLC. Some authors including the lead author were supported by a research grant to the Massachusetts General Hospital from Theracos Sub, LLC.

Source: Halvorsen YD et al. A 96-week, double-blind, randomized, controlled trial comparing bexagliflozin to glimepiride as an adjunct to metformin for the treatment of type 2 diabetes in adults. Diabetes Obes Metab. 2022 (Sep 30). Doi: 10.1111/dom.14875

Key clinical point: As an adjunct to metformin, bexagliflozin (20 mg) demonstrated antidiabetic potency equivalent to titrated glimepiride in patients with type 2 diabetes (T2D) inadequately controlled on metformin. Additional benefits were demonstrated in the form of weight loss, reduced systolic blood pressure (SBP), and fewer hypoglycemic events.

Major finding: At week 60, the least squares mean difference in glycated hemoglobin levels between bexagliflozin and glimepiride was −0.05% (95% CI −0.21% to 0.11%), showing noninferiority of bexagliflozin over glimepiride; however, bexagliflozin was superior to glimepiride for weight loss (P < .0001), decrease in SBP (P = .0008), and hypoglycemia incidence (P < .0001).

Study details: This 96-week randomized controlled trial included 426 patients with T2D (7.0% ≤ A1c ≤ 10.5%) inadequately controlled on metformin who were randomly assigned to receive bexagliflozin (n = 213) or titrated glimepiride (n = 213).

Disclosures: This study was funded by Theracos Sub, LLC. Some authors including the lead author were supported by a research grant to the Massachusetts General Hospital from Theracos Sub, LLC.

Source: Halvorsen YD et al. A 96-week, double-blind, randomized, controlled trial comparing bexagliflozin to glimepiride as an adjunct to metformin for the treatment of type 2 diabetes in adults. Diabetes Obes Metab. 2022 (Sep 30). Doi: 10.1111/dom.14875

Key clinical point: Patients with type 2 diabetes (T2D) who used sulfonylurea were at a higher risk for ventricular arrhythmia or sudden cardiac death (VA/SCD) compared with those who used metformin, irrespective of the severity of diabetes or history of coronary heart disease.

Major finding: Patients receiving sulfonylurea vs metformin had a significantly higher risk for VA/SCD (hazard ratio [HR] 1.90; 95% CI 1.73-2.08), with the results being consistent in both insulin users (HR 1.82; 95% CI 1.52-2.18) and nonusers (HR 1.92; 95% CI 1.73-2.13) and patients with (HR 1.64; 95% CI 1.34-2.02) and without (HR 1.95; 95% CI 1.76-2.16) coronary heart disease.

Study details: Findings are from a population-based cohort study including patients with T2D receiving metformin (n = 16,596) who were matched with those receiving sulfonylurea (n = 16,596) using propensity score matching.

Disclosures: This study did not receive any funding. The authors declared no competing interests.

Source: Lee TTL et al. Sulfonylurea is associated with higher risks of ventricular arrhythmia or sudden cardiac death compared with metformin: A population-based cohort study. J Am Heart Assoc. 2022;11(18):e026289 (Sep 14). Doi: 10.1161/JAHA.122.026289

Key clinical point: Patients with type 2 diabetes (T2D) who used sulfonylurea were at a higher risk for ventricular arrhythmia or sudden cardiac death (VA/SCD) compared with those who used metformin, irrespective of the severity of diabetes or history of coronary heart disease.

Major finding: Patients receiving sulfonylurea vs metformin had a significantly higher risk for VA/SCD (hazard ratio [HR] 1.90; 95% CI 1.73-2.08), with the results being consistent in both insulin users (HR 1.82; 95% CI 1.52-2.18) and nonusers (HR 1.92; 95% CI 1.73-2.13) and patients with (HR 1.64; 95% CI 1.34-2.02) and without (HR 1.95; 95% CI 1.76-2.16) coronary heart disease.

Study details: Findings are from a population-based cohort study including patients with T2D receiving metformin (n = 16,596) who were matched with those receiving sulfonylurea (n = 16,596) using propensity score matching.

Disclosures: This study did not receive any funding. The authors declared no competing interests.

Source: Lee TTL et al. Sulfonylurea is associated with higher risks of ventricular arrhythmia or sudden cardiac death compared with metformin: A population-based cohort study. J Am Heart Assoc. 2022;11(18):e026289 (Sep 14). Doi: 10.1161/JAHA.122.026289

Key clinical point: Patients with type 2 diabetes (T2D) who used sulfonylurea were at a higher risk for ventricular arrhythmia or sudden cardiac death (VA/SCD) compared with those who used metformin, irrespective of the severity of diabetes or history of coronary heart disease.

Major finding: Patients receiving sulfonylurea vs metformin had a significantly higher risk for VA/SCD (hazard ratio [HR] 1.90; 95% CI 1.73-2.08), with the results being consistent in both insulin users (HR 1.82; 95% CI 1.52-2.18) and nonusers (HR 1.92; 95% CI 1.73-2.13) and patients with (HR 1.64; 95% CI 1.34-2.02) and without (HR 1.95; 95% CI 1.76-2.16) coronary heart disease.

Study details: Findings are from a population-based cohort study including patients with T2D receiving metformin (n = 16,596) who were matched with those receiving sulfonylurea (n = 16,596) using propensity score matching.

Disclosures: This study did not receive any funding. The authors declared no competing interests.

Source: Lee TTL et al. Sulfonylurea is associated with higher risks of ventricular arrhythmia or sudden cardiac death compared with metformin: A population-based cohort study. J Am Heart Assoc. 2022;11(18):e026289 (Sep 14). Doi: 10.1161/JAHA.122.026289

Key clinical point: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) and sulfonylureas (SUs) provide better protection against fractures in patients with type 2 diabetes (T2D) compared with thiazolidinedione (TZD). Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and dipeptidyl peptidase-4 inhibitors (DPP-4is) increase fracture risk vs. GLP1-RAs.

Major finding: Compared with TZD, the risk for fracture was significantly lower with GLP1-RA (risk ratio [RR], 0.50; 95% CI, 0.31-0.79) and sulfonylurea (RR, 0.56; 95% CI, 0.41-0.77); however, the risk was significantly higher with DPP-4i (RR, 1.76; 95% CI, 1.21-2.55) and SGLT-2i (RR, 1.50; 95% CI, 1.05-2.16) vs. GLP1-RA.

Study details: The data come from a meta-analysis of 161 trials including 191,361 patients with T2D who reported 2,916 fractures.

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

Source: Tsai WH et al. Risk of fracture caused by anti-diabetic drugs in individuals with type 2 diabetes: A network meta-analysis. Diabetes Res Clin Pract. 2022;192:110082  (Sep 16). Doi: 10.1016/j.diabres.2022.110082.

Key clinical point: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) and sulfonylureas (SUs) provide better protection against fractures in patients with type 2 diabetes (T2D) compared with thiazolidinedione (TZD). Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and dipeptidyl peptidase-4 inhibitors (DPP-4is) increase fracture risk vs. GLP1-RAs.

Major finding: Compared with TZD, the risk for fracture was significantly lower with GLP1-RA (risk ratio [RR], 0.50; 95% CI, 0.31-0.79) and sulfonylurea (RR, 0.56; 95% CI, 0.41-0.77); however, the risk was significantly higher with DPP-4i (RR, 1.76; 95% CI, 1.21-2.55) and SGLT-2i (RR, 1.50; 95% CI, 1.05-2.16) vs. GLP1-RA.

Study details: The data come from a meta-analysis of 161 trials including 191,361 patients with T2D who reported 2,916 fractures.

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

Source: Tsai WH et al. Risk of fracture caused by anti-diabetic drugs in individuals with type 2 diabetes: A network meta-analysis. Diabetes Res Clin Pract. 2022;192:110082  (Sep 16). Doi: 10.1016/j.diabres.2022.110082.

Key clinical point: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) and sulfonylureas (SUs) provide better protection against fractures in patients with type 2 diabetes (T2D) compared with thiazolidinedione (TZD). Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and dipeptidyl peptidase-4 inhibitors (DPP-4is) increase fracture risk vs. GLP1-RAs.

Major finding: Compared with TZD, the risk for fracture was significantly lower with GLP1-RA (risk ratio [RR], 0.50; 95% CI, 0.31-0.79) and sulfonylurea (RR, 0.56; 95% CI, 0.41-0.77); however, the risk was significantly higher with DPP-4i (RR, 1.76; 95% CI, 1.21-2.55) and SGLT-2i (RR, 1.50; 95% CI, 1.05-2.16) vs. GLP1-RA.

Study details: The data come from a meta-analysis of 161 trials including 191,361 patients with T2D who reported 2,916 fractures.

Disclosures: This study received no specific funding. The authors declared no conflicts of interest.

Source: Tsai WH et al. Risk of fracture caused by anti-diabetic drugs in individuals with type 2 diabetes: A network meta-analysis. Diabetes Res Clin Pract. 2022;192:110082  (Sep 16). Doi: 10.1016/j.diabres.2022.110082.

Key clinical point: Once-weekly tirzepatide vs. insulin glargine slowed estimated glomerular filtration rate (eGFR) decline, and reduced urine albumin-creatinine ratio (UACR) and the risk for composite kidney outcomes in patients with type 2 diabetes (T2D) with varying degrees of chronic kidney disease and high cardiovascular risk.

Major finding: Combined tirzepatide vs. insulin glargine was associated with slower annual rates of eGFR decline (between-group difference [Δ], 2.2 [95% CI, 1.6-2.8] mL/min per 1.73 m²) and reduced UACR increase (Δ, −31.9%; 95% CI, −37.7% to −25.7%) and risk for composite kidney outcomes (hazard ratio, 0.58; 95% CI, 0.43-0.80).

Study details: This was a post hoc analysis of SURPASS-4 trial including 2,002 patients with T2D and high cardiovascular risk who were randomly assigned to receive once-weekly tirzepatide (5, 10, or 15 mg; n=997) or insulin glargine (n=1,005).

Disclosures: This study was funded by Eli Lilly and Company. Some authors declared receiving research grants, contract support, payment/honoraria for speaking, and/or consulting fees from various sources, including Eli Lilly. Some authors declared being employees and shareholders of Eli Lilly.

Source: Heerspink HJL et al. Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS-4 trial: Post-hoc analysis of an open-label, randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2022 (Sep 21). Doi: 10.1016/S2213-8587(22)00243-1.

Key clinical point: Once-weekly tirzepatide vs. insulin glargine slowed estimated glomerular filtration rate (eGFR) decline, and reduced urine albumin-creatinine ratio (UACR) and the risk for composite kidney outcomes in patients with type 2 diabetes (T2D) with varying degrees of chronic kidney disease and high cardiovascular risk.

Major finding: Combined tirzepatide vs. insulin glargine was associated with slower annual rates of eGFR decline (between-group difference [Δ], 2.2 [95% CI, 1.6-2.8] mL/min per 1.73 m²) and reduced UACR increase (Δ, −31.9%; 95% CI, −37.7% to −25.7%) and risk for composite kidney outcomes (hazard ratio, 0.58; 95% CI, 0.43-0.80).

Study details: This was a post hoc analysis of SURPASS-4 trial including 2,002 patients with T2D and high cardiovascular risk who were randomly assigned to receive once-weekly tirzepatide (5, 10, or 15 mg; n=997) or insulin glargine (n=1,005).

Disclosures: This study was funded by Eli Lilly and Company. Some authors declared receiving research grants, contract support, payment/honoraria for speaking, and/or consulting fees from various sources, including Eli Lilly. Some authors declared being employees and shareholders of Eli Lilly.

Source: Heerspink HJL et al. Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS-4 trial: Post-hoc analysis of an open-label, randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2022 (Sep 21). Doi: 10.1016/S2213-8587(22)00243-1.

Key clinical point: Once-weekly tirzepatide vs. insulin glargine slowed estimated glomerular filtration rate (eGFR) decline, and reduced urine albumin-creatinine ratio (UACR) and the risk for composite kidney outcomes in patients with type 2 diabetes (T2D) with varying degrees of chronic kidney disease and high cardiovascular risk.

Major finding: Combined tirzepatide vs. insulin glargine was associated with slower annual rates of eGFR decline (between-group difference [Δ], 2.2 [95% CI, 1.6-2.8] mL/min per 1.73 m²) and reduced UACR increase (Δ, −31.9%; 95% CI, −37.7% to −25.7%) and risk for composite kidney outcomes (hazard ratio, 0.58; 95% CI, 0.43-0.80).

Study details: This was a post hoc analysis of SURPASS-4 trial including 2,002 patients with T2D and high cardiovascular risk who were randomly assigned to receive once-weekly tirzepatide (5, 10, or 15 mg; n=997) or insulin glargine (n=1,005).

Disclosures: This study was funded by Eli Lilly and Company. Some authors declared receiving research grants, contract support, payment/honoraria for speaking, and/or consulting fees from various sources, including Eli Lilly. Some authors declared being employees and shareholders of Eli Lilly.

Source: Heerspink HJL et al. Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS-4 trial: Post-hoc analysis of an open-label, randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2022 (Sep 21). Doi: 10.1016/S2213-8587(22)00243-1.

Mind and body practices, especially yoga, improve glycemic control in type 2 diabetes to a similar extent as medications such as metformin, new research shows.

“To our knowledge, this is the first study that has looked across different modalities of mind-body interventions and the first to show that there is a very consistent effect on A1c regardless of which modality you use,” senior author, Richard Watanabe, PhD, professor of biostatistics, Keck School of Medicine of the University of Southern California, Los Angeles, told this news organization.

none needed

Regularity of yoga practice makes the difference

A total of 28 studies of patients with type 2 diabetes published between 1993 and 2022 were included in the meta-analysis. In all studies, patients who were taking insulin or had any medical complications of diabetes were excluded.

A significant mean reduction in A1c of 0.84% was observed across the board for all types of mindfulness interventions (P < .0001).

For mindfulness-based stress reduction, A1c was reduced by 0.48% (P = 0.03), while the practice of qigong – a coordinated body-posture movement – was associated with a 0.66% drop in A1c (P = .01). For meditation, A1c dropped by 0.50% (P = .64).

However, the largest drop in A1c was seen with yoga, where it fell by 1.00% (P < .0001) – about the same degree of glycemic control achieved with metformin, the authors point out.  

Indeed, for every additional day of yoga practiced per week, mean A1c differed by –0.22% (P = .46) between those who engaged in mind-body interventions and those who did not.

There was also a reduction in fasting blood glucose (FBG) with yoga and other practices. “The mean change in FBG was consistent with the mean change in A1c at –22.81 mg/dL (P < .0001),” the authors continue.

The researchers found that the duration of yoga didn’t matter but the frequency did, so it’s the regularity “with which you do yoga that makes the difference,” Dr. Watanabe said.

Dr. Watanabe and his coauthors also point out that because most patients were actively receiving metformin before and throughout the studies, the observed effect of mind and body practices on A1c represents an additional reduction beyond that of medication.

“This raises the question [as to] whether mind and body practices could be useful when initiated early in the course of diabetes therapy along with conventional lifestyle treatments,” they suggest.

While more research is needed to study this specifically, “our results suggest that these mind-body practices might be a good preventative measure,” Dr. Watanabe noted. Mind-body practices may also effectively prevent type 2 diabetes in at-risk patients, the authors propose.
 

Does meditation help alleviate psychological distress?

How mind-body practices work to improve glycemic control isn’t clear, but one possible theory is that patients experience a decrease in psychological distress when they undertake such practices and in so doing, may be more compliant with their prescribed treatment regimen.

A few of the studies analyzed showed that mind-body work resulted in a significant decrease in serum cortisol, the stress hormone that could plausibly mediate the benefit of mind and body practices through reduced inflammation.

In addition, “people with diabetes live with what we call ‘diabetes distress,’ ” Dr. Watanabe explained.

“Management of blood glucose is very stressful. You have to watch what you eat, you have to measure your glucose, and for the average person, that gets stressful. And that stress just contributes to the difficulty of controlling blood glucose,” he noted.

The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Mind and body practices, especially yoga, improve glycemic control in type 2 diabetes to a similar extent as medications such as metformin, new research shows.

“To our knowledge, this is the first study that has looked across different modalities of mind-body interventions and the first to show that there is a very consistent effect on A1c regardless of which modality you use,” senior author, Richard Watanabe, PhD, professor of biostatistics, Keck School of Medicine of the University of Southern California, Los Angeles, told this news organization.

none needed

Regularity of yoga practice makes the difference

A total of 28 studies of patients with type 2 diabetes published between 1993 and 2022 were included in the meta-analysis. In all studies, patients who were taking insulin or had any medical complications of diabetes were excluded.

A significant mean reduction in A1c of 0.84% was observed across the board for all types of mindfulness interventions (P < .0001).

For mindfulness-based stress reduction, A1c was reduced by 0.48% (P = 0.03), while the practice of qigong – a coordinated body-posture movement – was associated with a 0.66% drop in A1c (P = .01). For meditation, A1c dropped by 0.50% (P = .64).

However, the largest drop in A1c was seen with yoga, where it fell by 1.00% (P < .0001) – about the same degree of glycemic control achieved with metformin, the authors point out.  

Indeed, for every additional day of yoga practiced per week, mean A1c differed by –0.22% (P = .46) between those who engaged in mind-body interventions and those who did not.

There was also a reduction in fasting blood glucose (FBG) with yoga and other practices. “The mean change in FBG was consistent with the mean change in A1c at –22.81 mg/dL (P < .0001),” the authors continue.

The researchers found that the duration of yoga didn’t matter but the frequency did, so it’s the regularity “with which you do yoga that makes the difference,” Dr. Watanabe said.

Dr. Watanabe and his coauthors also point out that because most patients were actively receiving metformin before and throughout the studies, the observed effect of mind and body practices on A1c represents an additional reduction beyond that of medication.

“This raises the question [as to] whether mind and body practices could be useful when initiated early in the course of diabetes therapy along with conventional lifestyle treatments,” they suggest.

While more research is needed to study this specifically, “our results suggest that these mind-body practices might be a good preventative measure,” Dr. Watanabe noted. Mind-body practices may also effectively prevent type 2 diabetes in at-risk patients, the authors propose.
 

Does meditation help alleviate psychological distress?

How mind-body practices work to improve glycemic control isn’t clear, but one possible theory is that patients experience a decrease in psychological distress when they undertake such practices and in so doing, may be more compliant with their prescribed treatment regimen.

A few of the studies analyzed showed that mind-body work resulted in a significant decrease in serum cortisol, the stress hormone that could plausibly mediate the benefit of mind and body practices through reduced inflammation.

In addition, “people with diabetes live with what we call ‘diabetes distress,’ ” Dr. Watanabe explained.

“Management of blood glucose is very stressful. You have to watch what you eat, you have to measure your glucose, and for the average person, that gets stressful. And that stress just contributes to the difficulty of controlling blood glucose,” he noted.

The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Mind and body practices, especially yoga, improve glycemic control in type 2 diabetes to a similar extent as medications such as metformin, new research shows.

“To our knowledge, this is the first study that has looked across different modalities of mind-body interventions and the first to show that there is a very consistent effect on A1c regardless of which modality you use,” senior author, Richard Watanabe, PhD, professor of biostatistics, Keck School of Medicine of the University of Southern California, Los Angeles, told this news organization.

none needed

Regularity of yoga practice makes the difference

A total of 28 studies of patients with type 2 diabetes published between 1993 and 2022 were included in the meta-analysis. In all studies, patients who were taking insulin or had any medical complications of diabetes were excluded.

A significant mean reduction in A1c of 0.84% was observed across the board for all types of mindfulness interventions (P < .0001).

For mindfulness-based stress reduction, A1c was reduced by 0.48% (P = 0.03), while the practice of qigong – a coordinated body-posture movement – was associated with a 0.66% drop in A1c (P = .01). For meditation, A1c dropped by 0.50% (P = .64).

However, the largest drop in A1c was seen with yoga, where it fell by 1.00% (P < .0001) – about the same degree of glycemic control achieved with metformin, the authors point out.  

Indeed, for every additional day of yoga practiced per week, mean A1c differed by –0.22% (P = .46) between those who engaged in mind-body interventions and those who did not.

There was also a reduction in fasting blood glucose (FBG) with yoga and other practices. “The mean change in FBG was consistent with the mean change in A1c at –22.81 mg/dL (P < .0001),” the authors continue.

The researchers found that the duration of yoga didn’t matter but the frequency did, so it’s the regularity “with which you do yoga that makes the difference,” Dr. Watanabe said.

Dr. Watanabe and his coauthors also point out that because most patients were actively receiving metformin before and throughout the studies, the observed effect of mind and body practices on A1c represents an additional reduction beyond that of medication.

“This raises the question [as to] whether mind and body practices could be useful when initiated early in the course of diabetes therapy along with conventional lifestyle treatments,” they suggest.

While more research is needed to study this specifically, “our results suggest that these mind-body practices might be a good preventative measure,” Dr. Watanabe noted. Mind-body practices may also effectively prevent type 2 diabetes in at-risk patients, the authors propose.
 

Does meditation help alleviate psychological distress?

How mind-body practices work to improve glycemic control isn’t clear, but one possible theory is that patients experience a decrease in psychological distress when they undertake such practices and in so doing, may be more compliant with their prescribed treatment regimen.

A few of the studies analyzed showed that mind-body work resulted in a significant decrease in serum cortisol, the stress hormone that could plausibly mediate the benefit of mind and body practices through reduced inflammation.

In addition, “people with diabetes live with what we call ‘diabetes distress,’ ” Dr. Watanabe explained.

“Management of blood glucose is very stressful. You have to watch what you eat, you have to measure your glucose, and for the average person, that gets stressful. And that stress just contributes to the difficulty of controlling blood glucose,” he noted.

The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Researchers have developed a computer program to identify drugs for other diseases that might be repurposed to treat type 2 diabetes and/or obesity by targeting genetic pathways for these two conditions.

The scientists identified four pathways with known drug targets for type 2 diabetes and five with known drug targets for obesity.

Their findings suggest that:

• Palbociclib (used to treat breast cancer) and cardiac glycosides (used to treat heart failure and heart rhythm disorders) might be repurposed to treat type 2 diabetes.
• Baclofen (a muscle relaxant) and carfilzomib (a chemotherapy) could potentially be used to treat obesity.
• Fostamatinib (used to treat thrombocytopenia), sucralfate (used to treat stomach ulcers), and regorafenib (used to treat cancer) might be used to treat type 2 diabetes and obesity.
• Baclofen and sucralfate would have favorable safety profiles as repurposed treatments.

Sahar El Shair, a PhD student at the Faculty of Health and Medicine, University of Newcastle, New South Wales, Australia, presented the research during an oral session at the International Congress on Obesity, the biennial congress of the World Obesity Federation, in Melbourne.

“New treatments with higher activity and specificity are urgently needed to tackle a pandemic of chronic illness associated with type 2 diabetes and obesity,” senior coauthor Murray Cairns, PhD, said in a press release from the ICO.   

“Our technology harnesses genetically informed precision medicine to identify and target new treatments for these complex disorders,” said Dr. Cairns, from the school of biomedical sciences and pharmacy at the University of Newcastle.

Matchmaking between individual, their genetic traits, and drugs

Dr. Cairns and senior coauthor William Reay, PhD, also from the school of biomedical sciences and pharmacy, have cofounded a company called PolygenRx.

The company website explains that they have developed a propriety platform termed the pharmagenic enrichment score (PES), which is “essentially a matchmaking service between patients and drugs, allowing treatment to be optimized for each individual using their unique combination of genetic risk factors.”

It is important to note the genetic risk from complex traits, such as type 2 diabetes and obesity, “are quite different [from] the rare genetic disorders caused mostly by a devastating mutation in a single gene,” Dr. Cairns explained in an email.

“Complex traits,” he noted, “are associated with thousands of [genetic] variants that are common in people and have a cumulative effect.”

For this specific research, the investigators obtained genetic data from genome-wide association studies of obesity and type 2 diabetes.

“By using very large cohorts (hundreds of thousands of individuals) and comparing the frequency of millions of genetic variants in subjects with these conditions with controls, these studies have revealed regions of the genome and genes associated with the condition,” Dr. Cairns noted.

The pharmagenic enrichment score integrates a person’s genetics with drug pharmacology to determine if a person would respond more readily to a certain drug.

“We are investigating the potential of thousands of drugs across a broad spectrum of complex traits (the list is almost endless),” Dr. Cairns explained.

From the PES score, “we have an estimate of each individual’s likelihood of a positive response to said drug,” he noted. “We all have variants that increase (and decrease) the risk of these conditions to various degrees as they are common (high frequency) genetic variants.”

With this research, “we can implement this precision medicine strategy to match the right [repurposed] drugs for individuals based on their specific burden of genetic risk” for obesity and type 2 diabetes.

“Drug repurposing can be a fast track to new medicines because there is existing knowledge about their safety and activity in humans,” he said.

Next steps: Raising funds for clinical trials

“We would like to progress some of these compounds to preclinical and clinical trials,” Dr. Cairns said, “but need to raise the funds for this expensive research. With limited government research funding opportunities, we have recently spun out a startup company to attract commercial investment in our platform and the development of new drug candidates.”

The authors have reported no relevant financial relationships. Dr. Reay and Dr. Cairns are cofounders of PolygenRx.

A version of this article first appeared on Medscape.com.

Researchers have developed a computer program to identify drugs for other diseases that might be repurposed to treat type 2 diabetes and/or obesity by targeting genetic pathways for these two conditions.

The scientists identified four pathways with known drug targets for type 2 diabetes and five with known drug targets for obesity.

Their findings suggest that:

• Palbociclib (used to treat breast cancer) and cardiac glycosides (used to treat heart failure and heart rhythm disorders) might be repurposed to treat type 2 diabetes.
• Baclofen (a muscle relaxant) and carfilzomib (a chemotherapy) could potentially be used to treat obesity.
• Fostamatinib (used to treat thrombocytopenia), sucralfate (used to treat stomach ulcers), and regorafenib (used to treat cancer) might be used to treat type 2 diabetes and obesity.
• Baclofen and sucralfate would have favorable safety profiles as repurposed treatments.

Sahar El Shair, a PhD student at the Faculty of Health and Medicine, University of Newcastle, New South Wales, Australia, presented the research during an oral session at the International Congress on Obesity, the biennial congress of the World Obesity Federation, in Melbourne.

“New treatments with higher activity and specificity are urgently needed to tackle a pandemic of chronic illness associated with type 2 diabetes and obesity,” senior coauthor Murray Cairns, PhD, said in a press release from the ICO.   

“Our technology harnesses genetically informed precision medicine to identify and target new treatments for these complex disorders,” said Dr. Cairns, from the school of biomedical sciences and pharmacy at the University of Newcastle.

Matchmaking between individual, their genetic traits, and drugs

Dr. Cairns and senior coauthor William Reay, PhD, also from the school of biomedical sciences and pharmacy, have cofounded a company called PolygenRx.

The company website explains that they have developed a propriety platform termed the pharmagenic enrichment score (PES), which is “essentially a matchmaking service between patients and drugs, allowing treatment to be optimized for each individual using their unique combination of genetic risk factors.”

It is important to note the genetic risk from complex traits, such as type 2 diabetes and obesity, “are quite different [from] the rare genetic disorders caused mostly by a devastating mutation in a single gene,” Dr. Cairns explained in an email.

“Complex traits,” he noted, “are associated with thousands of [genetic] variants that are common in people and have a cumulative effect.”

For this specific research, the investigators obtained genetic data from genome-wide association studies of obesity and type 2 diabetes.

“By using very large cohorts (hundreds of thousands of individuals) and comparing the frequency of millions of genetic variants in subjects with these conditions with controls, these studies have revealed regions of the genome and genes associated with the condition,” Dr. Cairns noted.

The pharmagenic enrichment score integrates a person’s genetics with drug pharmacology to determine if a person would respond more readily to a certain drug.

“We are investigating the potential of thousands of drugs across a broad spectrum of complex traits (the list is almost endless),” Dr. Cairns explained.

From the PES score, “we have an estimate of each individual’s likelihood of a positive response to said drug,” he noted. “We all have variants that increase (and decrease) the risk of these conditions to various degrees as they are common (high frequency) genetic variants.”

With this research, “we can implement this precision medicine strategy to match the right [repurposed] drugs for individuals based on their specific burden of genetic risk” for obesity and type 2 diabetes.

“Drug repurposing can be a fast track to new medicines because there is existing knowledge about their safety and activity in humans,” he said.

Next steps: Raising funds for clinical trials

“We would like to progress some of these compounds to preclinical and clinical trials,” Dr. Cairns said, “but need to raise the funds for this expensive research. With limited government research funding opportunities, we have recently spun out a startup company to attract commercial investment in our platform and the development of new drug candidates.”

The authors have reported no relevant financial relationships. Dr. Reay and Dr. Cairns are cofounders of PolygenRx.

A version of this article first appeared on Medscape.com.

Researchers have developed a computer program to identify drugs for other diseases that might be repurposed to treat type 2 diabetes and/or obesity by targeting genetic pathways for these two conditions.

The scientists identified four pathways with known drug targets for type 2 diabetes and five with known drug targets for obesity.

Their findings suggest that:

• Palbociclib (used to treat breast cancer) and cardiac glycosides (used to treat heart failure and heart rhythm disorders) might be repurposed to treat type 2 diabetes.
• Baclofen (a muscle relaxant) and carfilzomib (a chemotherapy) could potentially be used to treat obesity.
• Fostamatinib (used to treat thrombocytopenia), sucralfate (used to treat stomach ulcers), and regorafenib (used to treat cancer) might be used to treat type 2 diabetes and obesity.
• Baclofen and sucralfate would have favorable safety profiles as repurposed treatments.

Sahar El Shair, a PhD student at the Faculty of Health and Medicine, University of Newcastle, New South Wales, Australia, presented the research during an oral session at the International Congress on Obesity, the biennial congress of the World Obesity Federation, in Melbourne.

“New treatments with higher activity and specificity are urgently needed to tackle a pandemic of chronic illness associated with type 2 diabetes and obesity,” senior coauthor Murray Cairns, PhD, said in a press release from the ICO.   

“Our technology harnesses genetically informed precision medicine to identify and target new treatments for these complex disorders,” said Dr. Cairns, from the school of biomedical sciences and pharmacy at the University of Newcastle.

Matchmaking between individual, their genetic traits, and drugs

Dr. Cairns and senior coauthor William Reay, PhD, also from the school of biomedical sciences and pharmacy, have cofounded a company called PolygenRx.

The company website explains that they have developed a propriety platform termed the pharmagenic enrichment score (PES), which is “essentially a matchmaking service between patients and drugs, allowing treatment to be optimized for each individual using their unique combination of genetic risk factors.”

It is important to note the genetic risk from complex traits, such as type 2 diabetes and obesity, “are quite different [from] the rare genetic disorders caused mostly by a devastating mutation in a single gene,” Dr. Cairns explained in an email.

“Complex traits,” he noted, “are associated with thousands of [genetic] variants that are common in people and have a cumulative effect.”

For this specific research, the investigators obtained genetic data from genome-wide association studies of obesity and type 2 diabetes.

“By using very large cohorts (hundreds of thousands of individuals) and comparing the frequency of millions of genetic variants in subjects with these conditions with controls, these studies have revealed regions of the genome and genes associated with the condition,” Dr. Cairns noted.

The pharmagenic enrichment score integrates a person’s genetics with drug pharmacology to determine if a person would respond more readily to a certain drug.

“We are investigating the potential of thousands of drugs across a broad spectrum of complex traits (the list is almost endless),” Dr. Cairns explained.

From the PES score, “we have an estimate of each individual’s likelihood of a positive response to said drug,” he noted. “We all have variants that increase (and decrease) the risk of these conditions to various degrees as they are common (high frequency) genetic variants.”

With this research, “we can implement this precision medicine strategy to match the right [repurposed] drugs for individuals based on their specific burden of genetic risk” for obesity and type 2 diabetes.

“Drug repurposing can be a fast track to new medicines because there is existing knowledge about their safety and activity in humans,” he said.

Next steps: Raising funds for clinical trials

“We would like to progress some of these compounds to preclinical and clinical trials,” Dr. Cairns said, “but need to raise the funds for this expensive research. With limited government research funding opportunities, we have recently spun out a startup company to attract commercial investment in our platform and the development of new drug candidates.”

The authors have reported no relevant financial relationships. Dr. Reay and Dr. Cairns are cofounders of PolygenRx.

A version of this article first appeared on Medscape.com.

Transplantation of cadaveric pancreatic islet cells resulted in graft survival and function with acceptable safety for up to 8 years in selected individuals with type 1 diabetes, new research finds.

The study is a long-term follow-up of two phase 3 pivotal trials from the Clinical Islet Transplantation Consortium of a purified human pancreatic islet cell product for treating people with type 1 diabetes.

One trial involved islet transplantation in 48 people who experienced severe hypoglycemia and hypoglycemic unawareness, and the other trial included 24 people who also experienced those complications and were already receiving immunosuppression following kidney transplant. The trials, both registered with the U.S. Food and Drug Administration (FDA), met their primary efficacy and safety endpoints at 2- and 3-year timepoints.

The follow-up data have now been published in Diabetes Care by Michael Rickels, MD, and colleagues.

The procedure involved infusion through the hepatic portal vein of one or more purified human pancreatic islet products under standardized immunosuppression using methods that Dr. Rickels and colleagues have been developing since 2004. The approach involves multiple modalities to protect the islets prior to transplantation.

Among the 34 islet-alone and eight islet-after–kidney transplant recipients who entered the extended follow-up, durable graft survival allowing for achievement of glycemic targets occurred without severe hypoglycemia or adverse effects from immunosuppression.

The primary outcome, actuarial survival of graft islet function, was 56% at the maximum follow-up of 8.3 years for the islet-only transplantation group and 49% at 7.3 years for the islet-after–kidney transplantation group (P = .004).

The findings suggest that “in the long run, islet transplantation has efficacy, including among those who have had kidney transplants ... Most type 1 diabetes patients are improved tremendously with current insulin delivery systems ... but for those having the most difficulty controlling their blood sugar – and those whose diabetes has already been complicated by needing a kidney transplant – the outcomes we saw in this study are what we’ve been hoping to achieve for more than 20 years,” said Dr. Rickels in a statement from his institution, the University of Pennsylvania, Philadelphia.

In the initial trials at day 75 after the initial transplant, 87.5% of the islet-alone and 71% of the islet-after–kidney transplant group achieved hemoglobin A1c under 7%, and 85% and 54%, respectively, achieved A1c at or under 6.5%. At the end of maximal follow-up, 49% of islet-only transplant recipients maintained A1c under 7%, although none had A1c at or under 6.5%. For the islet-after–kidney transplant group, these proportions were 35% and 17%, respectively (P = .0017 for A1c under 7.0% and P < .0001 for A1c ≤ 6.5%, respectively, between the groups).

There were 12 severe hypoglycemic episodes in five patients (three islet-alone and two islet-after–kidney transplant group) during the initial trials, but no additional episodes occurred in either group during long-term follow-up.  

Overall, 53 individuals – 37 in the islet-alone and 16 in the islet-after–kidney transplant group – or 74% of the total, achieved a period of insulin independence with A1c under 7%, ranging from 36 to 481 days. The range of time to achieving insulin independence reflects individuals who received one, two, or three islet infusions.

The fact that most patients achieved insulin independence following just one (n = 20) or two (n = 30) infusions and only three patients required three infusions was notable, Dr. Rickels said.

“Currently, around the world, there’s an expectation of two to three donor pancreases being needed. Here, it’s one, maybe two. It’s a much more efficient protocol and opens up access for more islet transplantation as a hoped-for alternative to pancreas transplants.”

Of those who achieved insulin independence, 30 (57%) remained insulin-independent throughout follow-up (20 of 37 islet-alone and 10 of 16 islet-after–kidney transplant patients), with no difference in duration of insulin independence between the groups.

There were no deaths during post-transplant follow-up. Rates of serious adverse events were 0.31 and 0.43 per patient-year for the islet-after–kidney and islet-alone transplant groups, respectively. Of a total of 104 serious adverse events, 65 occurred during the initial trials and had been previously reported. Of the additional 39 serious adverse events that occurred during long-term follow-up, 11 were possibly due to immunosuppression and 27 were deemed unrelated to the procedures.

According to Dr. Rickels, “These are the most seriously affected patients, and you’d be expecting to see some hospitalizations in a population managed on immunosuppression therapy ... It’s important to note that none of the adverse events were related to the actual islet product. Also, kidney function remained stable during long-term follow-up in both cohorts, in fact, improving in those who had kidney transplants.”

Overall, he said, “This is a much less invasive procedure that opens itself up to significantly fewer complications than what many of these patients would otherwise require, a pancreas transplant, which involves major abdominal surgery.”

The investigators plan to submit these data as part of a biologic license application (BLA) to the FDA.

The research was supported by grants from JDRF, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of Allergy and Infectious Diseases. Dr. Rickels has reported receiving consulting fees from Sernova and Vertex Pharmaceuticals.

A version of this article first appeared on Medscape.com.

Transplantation of cadaveric pancreatic islet cells resulted in graft survival and function with acceptable safety for up to 8 years in selected individuals with type 1 diabetes, new research finds.

The study is a long-term follow-up of two phase 3 pivotal trials from the Clinical Islet Transplantation Consortium of a purified human pancreatic islet cell product for treating people with type 1 diabetes.

One trial involved islet transplantation in 48 people who experienced severe hypoglycemia and hypoglycemic unawareness, and the other trial included 24 people who also experienced those complications and were already receiving immunosuppression following kidney transplant. The trials, both registered with the U.S. Food and Drug Administration (FDA), met their primary efficacy and safety endpoints at 2- and 3-year timepoints.

The follow-up data have now been published in Diabetes Care by Michael Rickels, MD, and colleagues.

The procedure involved infusion through the hepatic portal vein of one or more purified human pancreatic islet products under standardized immunosuppression using methods that Dr. Rickels and colleagues have been developing since 2004. The approach involves multiple modalities to protect the islets prior to transplantation.

Among the 34 islet-alone and eight islet-after–kidney transplant recipients who entered the extended follow-up, durable graft survival allowing for achievement of glycemic targets occurred without severe hypoglycemia or adverse effects from immunosuppression.

The primary outcome, actuarial survival of graft islet function, was 56% at the maximum follow-up of 8.3 years for the islet-only transplantation group and 49% at 7.3 years for the islet-after–kidney transplantation group (P = .004).

The findings suggest that “in the long run, islet transplantation has efficacy, including among those who have had kidney transplants ... Most type 1 diabetes patients are improved tremendously with current insulin delivery systems ... but for those having the most difficulty controlling their blood sugar – and those whose diabetes has already been complicated by needing a kidney transplant – the outcomes we saw in this study are what we’ve been hoping to achieve for more than 20 years,” said Dr. Rickels in a statement from his institution, the University of Pennsylvania, Philadelphia.

In the initial trials at day 75 after the initial transplant, 87.5% of the islet-alone and 71% of the islet-after–kidney transplant group achieved hemoglobin A1c under 7%, and 85% and 54%, respectively, achieved A1c at or under 6.5%. At the end of maximal follow-up, 49% of islet-only transplant recipients maintained A1c under 7%, although none had A1c at or under 6.5%. For the islet-after–kidney transplant group, these proportions were 35% and 17%, respectively (P = .0017 for A1c under 7.0% and P < .0001 for A1c ≤ 6.5%, respectively, between the groups).

There were 12 severe hypoglycemic episodes in five patients (three islet-alone and two islet-after–kidney transplant group) during the initial trials, but no additional episodes occurred in either group during long-term follow-up.  

Overall, 53 individuals – 37 in the islet-alone and 16 in the islet-after–kidney transplant group – or 74% of the total, achieved a period of insulin independence with A1c under 7%, ranging from 36 to 481 days. The range of time to achieving insulin independence reflects individuals who received one, two, or three islet infusions.

The fact that most patients achieved insulin independence following just one (n = 20) or two (n = 30) infusions and only three patients required three infusions was notable, Dr. Rickels said.

“Currently, around the world, there’s an expectation of two to three donor pancreases being needed. Here, it’s one, maybe two. It’s a much more efficient protocol and opens up access for more islet transplantation as a hoped-for alternative to pancreas transplants.”

Of those who achieved insulin independence, 30 (57%) remained insulin-independent throughout follow-up (20 of 37 islet-alone and 10 of 16 islet-after–kidney transplant patients), with no difference in duration of insulin independence between the groups.

There were no deaths during post-transplant follow-up. Rates of serious adverse events were 0.31 and 0.43 per patient-year for the islet-after–kidney and islet-alone transplant groups, respectively. Of a total of 104 serious adverse events, 65 occurred during the initial trials and had been previously reported. Of the additional 39 serious adverse events that occurred during long-term follow-up, 11 were possibly due to immunosuppression and 27 were deemed unrelated to the procedures.

According to Dr. Rickels, “These are the most seriously affected patients, and you’d be expecting to see some hospitalizations in a population managed on immunosuppression therapy ... It’s important to note that none of the adverse events were related to the actual islet product. Also, kidney function remained stable during long-term follow-up in both cohorts, in fact, improving in those who had kidney transplants.”

Overall, he said, “This is a much less invasive procedure that opens itself up to significantly fewer complications than what many of these patients would otherwise require, a pancreas transplant, which involves major abdominal surgery.”

The investigators plan to submit these data as part of a biologic license application (BLA) to the FDA.

The research was supported by grants from JDRF, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of Allergy and Infectious Diseases. Dr. Rickels has reported receiving consulting fees from Sernova and Vertex Pharmaceuticals.

A version of this article first appeared on Medscape.com.

Transplantation of cadaveric pancreatic islet cells resulted in graft survival and function with acceptable safety for up to 8 years in selected individuals with type 1 diabetes, new research finds.

The study is a long-term follow-up of two phase 3 pivotal trials from the Clinical Islet Transplantation Consortium of a purified human pancreatic islet cell product for treating people with type 1 diabetes.

One trial involved islet transplantation in 48 people who experienced severe hypoglycemia and hypoglycemic unawareness, and the other trial included 24 people who also experienced those complications and were already receiving immunosuppression following kidney transplant. The trials, both registered with the U.S. Food and Drug Administration (FDA), met their primary efficacy and safety endpoints at 2- and 3-year timepoints.

The follow-up data have now been published in Diabetes Care by Michael Rickels, MD, and colleagues.

The procedure involved infusion through the hepatic portal vein of one or more purified human pancreatic islet products under standardized immunosuppression using methods that Dr. Rickels and colleagues have been developing since 2004. The approach involves multiple modalities to protect the islets prior to transplantation.

Among the 34 islet-alone and eight islet-after–kidney transplant recipients who entered the extended follow-up, durable graft survival allowing for achievement of glycemic targets occurred without severe hypoglycemia or adverse effects from immunosuppression.

The primary outcome, actuarial survival of graft islet function, was 56% at the maximum follow-up of 8.3 years for the islet-only transplantation group and 49% at 7.3 years for the islet-after–kidney transplantation group (P = .004).

The findings suggest that “in the long run, islet transplantation has efficacy, including among those who have had kidney transplants ... Most type 1 diabetes patients are improved tremendously with current insulin delivery systems ... but for those having the most difficulty controlling their blood sugar – and those whose diabetes has already been complicated by needing a kidney transplant – the outcomes we saw in this study are what we’ve been hoping to achieve for more than 20 years,” said Dr. Rickels in a statement from his institution, the University of Pennsylvania, Philadelphia.

In the initial trials at day 75 after the initial transplant, 87.5% of the islet-alone and 71% of the islet-after–kidney transplant group achieved hemoglobin A1c under 7%, and 85% and 54%, respectively, achieved A1c at or under 6.5%. At the end of maximal follow-up, 49% of islet-only transplant recipients maintained A1c under 7%, although none had A1c at or under 6.5%. For the islet-after–kidney transplant group, these proportions were 35% and 17%, respectively (P = .0017 for A1c under 7.0% and P < .0001 for A1c ≤ 6.5%, respectively, between the groups).

There were 12 severe hypoglycemic episodes in five patients (three islet-alone and two islet-after–kidney transplant group) during the initial trials, but no additional episodes occurred in either group during long-term follow-up.  

Overall, 53 individuals – 37 in the islet-alone and 16 in the islet-after–kidney transplant group – or 74% of the total, achieved a period of insulin independence with A1c under 7%, ranging from 36 to 481 days. The range of time to achieving insulin independence reflects individuals who received one, two, or three islet infusions.

The fact that most patients achieved insulin independence following just one (n = 20) or two (n = 30) infusions and only three patients required three infusions was notable, Dr. Rickels said.

“Currently, around the world, there’s an expectation of two to three donor pancreases being needed. Here, it’s one, maybe two. It’s a much more efficient protocol and opens up access for more islet transplantation as a hoped-for alternative to pancreas transplants.”

Of those who achieved insulin independence, 30 (57%) remained insulin-independent throughout follow-up (20 of 37 islet-alone and 10 of 16 islet-after–kidney transplant patients), with no difference in duration of insulin independence between the groups.

There were no deaths during post-transplant follow-up. Rates of serious adverse events were 0.31 and 0.43 per patient-year for the islet-after–kidney and islet-alone transplant groups, respectively. Of a total of 104 serious adverse events, 65 occurred during the initial trials and had been previously reported. Of the additional 39 serious adverse events that occurred during long-term follow-up, 11 were possibly due to immunosuppression and 27 were deemed unrelated to the procedures.

According to Dr. Rickels, “These are the most seriously affected patients, and you’d be expecting to see some hospitalizations in a population managed on immunosuppression therapy ... It’s important to note that none of the adverse events were related to the actual islet product. Also, kidney function remained stable during long-term follow-up in both cohorts, in fact, improving in those who had kidney transplants.”

Overall, he said, “This is a much less invasive procedure that opens itself up to significantly fewer complications than what many of these patients would otherwise require, a pancreas transplant, which involves major abdominal surgery.”

The investigators plan to submit these data as part of a biologic license application (BLA) to the FDA.

The research was supported by grants from JDRF, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of Allergy and Infectious Diseases. Dr. Rickels has reported receiving consulting fees from Sernova and Vertex Pharmaceuticals.

A version of this article first appeared on Medscape.com.

Insulin rationing due to cost in the United States is common even among people with diabetes who have private health insurance, new data show.

The findings from the 2021 National Health Interview Survey (NHIS) suggest that about one in six people with insulin-treated diabetes in the United States practice insulin rationing – skipping doses, taking less insulin than needed, or delaying the purchase of insulin – because of the price.

Not surprisingly, those without insurance had the highest rationing rate, at nearly a third. However, those with private insurance also had higher rates, at nearly one in five, than those of the overall diabetes population. And those with public insurance – Medicare and Medicaid – had lower rates.

The finding regarding privately insured individuals was “somewhat surprising,” lead author Adam Gaffney, MD, told this news organization. But he noted that the finding likely reflects issues such as copays and deductibles, along with other barriers patients experience within the private health insurance system.

The authors pointed out that the $35 copay cap on insulin included in the Inflation Reduction Act of 2022 might improve insulin access for Medicare beneficiaries but a similar cap for privately insured people was removed from the bill. Moreover, copay caps don’t help people who are uninsured.

And, although some states have also passed insulin copay caps that apply to privately insured people, “even a monthly cost of $35 can be a lot of money for people with low incomes. That isn’t negligible. It’s important to keep that in mind,” said Dr. Gaffney, a pulmonary and critical care physician at Harvard Medical School, Boston, and Cambridge (Mass.) Health Alliance.

“Insulin rationing is frequently harmful and sometimes deadly. In the ICU, I have cared for patients who have life-threatening complications of diabetes because they couldn’t afford this life-saving drug. Universal access to insulin, without cost barriers, is urgently needed,” Dr. Gaffney said in a Public Citizen statement.

Senior author Steffie Woolhandler, MD, agrees. “Drug companies have ramped up prices on insulin year after year, even for products that remain completely unchanged,” she noted.

“Drug firms are making vast profits at the expense of the health, and even the lives, of patients,” noted Dr. Woolhandler, a distinguished professor at Hunter College, City University of New York, a lecturer in medicine at Harvard, and a research associate at Public Citizen.
 

Uninsured, privately insured, and younger people more likely to ration

Dr. Gaffney and colleagues’ findings were published online in Annals of Internal Medicine.

The study is the first to examine insulin rationing across the United States among people with all diabetes types treated with insulin using the nationally representative NHIS data.

The results are consistent with those of previous studies, which have found similar rates of insulin rationing at a single U.S. institution and internationally among just those with type 1 diabetes, Dr. Gaffney noted.

In 2021, questions about insulin rationing were added to the NHIS for the first time.

The sample included 982 insulin users with diabetes, representing about 1.4 million U.S. adults with type 1 diabetes, 5.8 million with type 2 diabetes, and 0.4 million with other/unknown types.

Overall, 16.5% of participants – 1.3 million nationwide – reported skipping or reducing insulin doses or delaying the purchase of it in the past year. Delaying purchase was the most common type of rationing, reported by 14.2%, while taking less than needed was the most common practice among those with type 1 diabetes (16.5%).

Age made a difference, with 11.2% of adults aged 65 or older versus 20.4% of younger people reporting rationing. And by income level, even among those at the top level examined – 400% or higher of the federal poverty line – 10.8% reported rationing.

“The high-income group is not necessarily rich. Many would be considered middle-income,” Dr. Gaffney pointed out.  

By race, 23.2% of Black participants reported rationing compared with 16.0% of White and Hispanic individuals.

People without insurance had the highest rationing rate (29.2%), followed by those with private insurance (18.8%), other coverage (16.1%), Medicare (13.5%), and Medicaid (11.6%).
 

‘It’s a complicated system’

Dr. Gaffney noted that even when the patient has private insurance, it’s challenging for the clinician to know in advance whether there are formulary restrictions on what type of insulin can be prescribed or what the patient’s copay or deductible will be.

“Often the prescription gets written without clear knowledge of coverage beforehand ... Coverage differs from patient to patient, from insurance to insurance. It’s a complicated system.”

He added, though, that some electronic health records (EHRs) incorporate this information. “Currently, some EHRs give real-time feedback. I see no reason why, for all the money we plug into these EHRs, there couldn’t be real-time feedback for every patient so you know what the copay is and whether it’s covered at the time you’re prescribing it. To me that’s a very straightforward technological fix that we could achieve. We have the information, but it’s hard to act on it.”

But beyond the EHR, “there are also problems when the patient’s insurance changes or their network changes, and what insulin is covered changes. And they don’t necessarily get that new prescription in time. And suddenly they have a gap. Gaps can be dangerous.”  

What’s more, Dr. Gaffney noted: “The study raises concerning questions about what happens when the public health emergency ends and millions of people with Medicaid lose their coverage. Where are they going to get insulin? That’s another population we have to be worried about.”

All of this puts clinicians in a difficult spot, he said.

“They want the best for their patients but they’re working in a system that’s not letting them focus on practicing medicine and instead is forcing them to think about these economic issues that are in large part out of their control.”

Dr. Gaffney is a member of Physicians for a National Health Program, which advocates for a single-payer health system in the United States.

A version of this article first appeared on Medscape.com.

Insulin rationing due to cost in the United States is common even among people with diabetes who have private health insurance, new data show.

The findings from the 2021 National Health Interview Survey (NHIS) suggest that about one in six people with insulin-treated diabetes in the United States practice insulin rationing – skipping doses, taking less insulin than needed, or delaying the purchase of insulin – because of the price.

Not surprisingly, those without insurance had the highest rationing rate, at nearly a third. However, those with private insurance also had higher rates, at nearly one in five, than those of the overall diabetes population. And those with public insurance – Medicare and Medicaid – had lower rates.

The finding regarding privately insured individuals was “somewhat surprising,” lead author Adam Gaffney, MD, told this news organization. But he noted that the finding likely reflects issues such as copays and deductibles, along with other barriers patients experience within the private health insurance system.

The authors pointed out that the $35 copay cap on insulin included in the Inflation Reduction Act of 2022 might improve insulin access for Medicare beneficiaries but a similar cap for privately insured people was removed from the bill. Moreover, copay caps don’t help people who are uninsured.

And, although some states have also passed insulin copay caps that apply to privately insured people, “even a monthly cost of $35 can be a lot of money for people with low incomes. That isn’t negligible. It’s important to keep that in mind,” said Dr. Gaffney, a pulmonary and critical care physician at Harvard Medical School, Boston, and Cambridge (Mass.) Health Alliance.

“Insulin rationing is frequently harmful and sometimes deadly. In the ICU, I have cared for patients who have life-threatening complications of diabetes because they couldn’t afford this life-saving drug. Universal access to insulin, without cost barriers, is urgently needed,” Dr. Gaffney said in a Public Citizen statement.

Senior author Steffie Woolhandler, MD, agrees. “Drug companies have ramped up prices on insulin year after year, even for products that remain completely unchanged,” she noted.

“Drug firms are making vast profits at the expense of the health, and even the lives, of patients,” noted Dr. Woolhandler, a distinguished professor at Hunter College, City University of New York, a lecturer in medicine at Harvard, and a research associate at Public Citizen.
 

Uninsured, privately insured, and younger people more likely to ration

Dr. Gaffney and colleagues’ findings were published online in Annals of Internal Medicine.

The study is the first to examine insulin rationing across the United States among people with all diabetes types treated with insulin using the nationally representative NHIS data.

The results are consistent with those of previous studies, which have found similar rates of insulin rationing at a single U.S. institution and internationally among just those with type 1 diabetes, Dr. Gaffney noted.

In 2021, questions about insulin rationing were added to the NHIS for the first time.

The sample included 982 insulin users with diabetes, representing about 1.4 million U.S. adults with type 1 diabetes, 5.8 million with type 2 diabetes, and 0.4 million with other/unknown types.

Overall, 16.5% of participants – 1.3 million nationwide – reported skipping or reducing insulin doses or delaying the purchase of it in the past year. Delaying purchase was the most common type of rationing, reported by 14.2%, while taking less than needed was the most common practice among those with type 1 diabetes (16.5%).

Age made a difference, with 11.2% of adults aged 65 or older versus 20.4% of younger people reporting rationing. And by income level, even among those at the top level examined – 400% or higher of the federal poverty line – 10.8% reported rationing.

“The high-income group is not necessarily rich. Many would be considered middle-income,” Dr. Gaffney pointed out.  

By race, 23.2% of Black participants reported rationing compared with 16.0% of White and Hispanic individuals.

People without insurance had the highest rationing rate (29.2%), followed by those with private insurance (18.8%), other coverage (16.1%), Medicare (13.5%), and Medicaid (11.6%).
 

‘It’s a complicated system’

Dr. Gaffney noted that even when the patient has private insurance, it’s challenging for the clinician to know in advance whether there are formulary restrictions on what type of insulin can be prescribed or what the patient’s copay or deductible will be.

“Often the prescription gets written without clear knowledge of coverage beforehand ... Coverage differs from patient to patient, from insurance to insurance. It’s a complicated system.”

He added, though, that some electronic health records (EHRs) incorporate this information. “Currently, some EHRs give real-time feedback. I see no reason why, for all the money we plug into these EHRs, there couldn’t be real-time feedback for every patient so you know what the copay is and whether it’s covered at the time you’re prescribing it. To me that’s a very straightforward technological fix that we could achieve. We have the information, but it’s hard to act on it.”

But beyond the EHR, “there are also problems when the patient’s insurance changes or their network changes, and what insulin is covered changes. And they don’t necessarily get that new prescription in time. And suddenly they have a gap. Gaps can be dangerous.”  

What’s more, Dr. Gaffney noted: “The study raises concerning questions about what happens when the public health emergency ends and millions of people with Medicaid lose their coverage. Where are they going to get insulin? That’s another population we have to be worried about.”

All of this puts clinicians in a difficult spot, he said.

“They want the best for their patients but they’re working in a system that’s not letting them focus on practicing medicine and instead is forcing them to think about these economic issues that are in large part out of their control.”

Dr. Gaffney is a member of Physicians for a National Health Program, which advocates for a single-payer health system in the United States.

A version of this article first appeared on Medscape.com.

Insulin rationing due to cost in the United States is common even among people with diabetes who have private health insurance, new data show.

The findings from the 2021 National Health Interview Survey (NHIS) suggest that about one in six people with insulin-treated diabetes in the United States practice insulin rationing – skipping doses, taking less insulin than needed, or delaying the purchase of insulin – because of the price.

Not surprisingly, those without insurance had the highest rationing rate, at nearly a third. However, those with private insurance also had higher rates, at nearly one in five, than those of the overall diabetes population. And those with public insurance – Medicare and Medicaid – had lower rates.

The finding regarding privately insured individuals was “somewhat surprising,” lead author Adam Gaffney, MD, told this news organization. But he noted that the finding likely reflects issues such as copays and deductibles, along with other barriers patients experience within the private health insurance system.

The authors pointed out that the $35 copay cap on insulin included in the Inflation Reduction Act of 2022 might improve insulin access for Medicare beneficiaries but a similar cap for privately insured people was removed from the bill. Moreover, copay caps don’t help people who are uninsured.

And, although some states have also passed insulin copay caps that apply to privately insured people, “even a monthly cost of $35 can be a lot of money for people with low incomes. That isn’t negligible. It’s important to keep that in mind,” said Dr. Gaffney, a pulmonary and critical care physician at Harvard Medical School, Boston, and Cambridge (Mass.) Health Alliance.

“Insulin rationing is frequently harmful and sometimes deadly. In the ICU, I have cared for patients who have life-threatening complications of diabetes because they couldn’t afford this life-saving drug. Universal access to insulin, without cost barriers, is urgently needed,” Dr. Gaffney said in a Public Citizen statement.

Senior author Steffie Woolhandler, MD, agrees. “Drug companies have ramped up prices on insulin year after year, even for products that remain completely unchanged,” she noted.

“Drug firms are making vast profits at the expense of the health, and even the lives, of patients,” noted Dr. Woolhandler, a distinguished professor at Hunter College, City University of New York, a lecturer in medicine at Harvard, and a research associate at Public Citizen.
 

Uninsured, privately insured, and younger people more likely to ration

Dr. Gaffney and colleagues’ findings were published online in Annals of Internal Medicine.

The study is the first to examine insulin rationing across the United States among people with all diabetes types treated with insulin using the nationally representative NHIS data.

The results are consistent with those of previous studies, which have found similar rates of insulin rationing at a single U.S. institution and internationally among just those with type 1 diabetes, Dr. Gaffney noted.

In 2021, questions about insulin rationing were added to the NHIS for the first time.

The sample included 982 insulin users with diabetes, representing about 1.4 million U.S. adults with type 1 diabetes, 5.8 million with type 2 diabetes, and 0.4 million with other/unknown types.

Overall, 16.5% of participants – 1.3 million nationwide – reported skipping or reducing insulin doses or delaying the purchase of it in the past year. Delaying purchase was the most common type of rationing, reported by 14.2%, while taking less than needed was the most common practice among those with type 1 diabetes (16.5%).

Age made a difference, with 11.2% of adults aged 65 or older versus 20.4% of younger people reporting rationing. And by income level, even among those at the top level examined – 400% or higher of the federal poverty line – 10.8% reported rationing.

“The high-income group is not necessarily rich. Many would be considered middle-income,” Dr. Gaffney pointed out.  

By race, 23.2% of Black participants reported rationing compared with 16.0% of White and Hispanic individuals.

People without insurance had the highest rationing rate (29.2%), followed by those with private insurance (18.8%), other coverage (16.1%), Medicare (13.5%), and Medicaid (11.6%).
 

‘It’s a complicated system’

Dr. Gaffney noted that even when the patient has private insurance, it’s challenging for the clinician to know in advance whether there are formulary restrictions on what type of insulin can be prescribed or what the patient’s copay or deductible will be.

“Often the prescription gets written without clear knowledge of coverage beforehand ... Coverage differs from patient to patient, from insurance to insurance. It’s a complicated system.”

He added, though, that some electronic health records (EHRs) incorporate this information. “Currently, some EHRs give real-time feedback. I see no reason why, for all the money we plug into these EHRs, there couldn’t be real-time feedback for every patient so you know what the copay is and whether it’s covered at the time you’re prescribing it. To me that’s a very straightforward technological fix that we could achieve. We have the information, but it’s hard to act on it.”

But beyond the EHR, “there are also problems when the patient’s insurance changes or their network changes, and what insulin is covered changes. And they don’t necessarily get that new prescription in time. And suddenly they have a gap. Gaps can be dangerous.”  

What’s more, Dr. Gaffney noted: “The study raises concerning questions about what happens when the public health emergency ends and millions of people with Medicaid lose their coverage. Where are they going to get insulin? That’s another population we have to be worried about.”

All of this puts clinicians in a difficult spot, he said.

“They want the best for their patients but they’re working in a system that’s not letting them focus on practicing medicine and instead is forcing them to think about these economic issues that are in large part out of their control.”

Dr. Gaffney is a member of Physicians for a National Health Program, which advocates for a single-payer health system in the United States.

A version of this article first appeared on Medscape.com.

Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.

Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.

Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.