Glycemic variability remains a concern even in T2D patients with well-controlled glucose status

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Key clinical point: Greater glycemic variability measured as the coefficient of variation for glucose (%CV) level was associated with a higher risk for all-cause mortality in patients with type 2 diabetes (T2D) and a well-controlled glucose status.

 

Major finding: Compared with patients with a %CV level of ≤20%, those with a %CV level of 20%-25% (adjusted HR [aHR] 1.16; 95% CI 0.78-1.73), 25%-30% (aHR 1.38; 95% CI 0.89-2.15), 30%-35% (aHR 1.33; 95% CI 0.77-2.29), and >35% (aHR 2.26; 95% CI 1.13-4.52) had a higher risk for all-cause mortality.

 

Study details: This study was a part of the INDIGO study including 1839 patients with T2D who reached continuous glucose monitoring glycemic targets and were classified into five groups by %CV level.

 

Disclosures: This study was supported by the National Key R&D Program of China, the National Natural Science Foundation of China, and others. The authors declared no conflicts of interest.

 

Source: Mo Y et al. Impact of short-term glycemic variability on risk of all-cause mortality in type 2 diabetes patients with well-controlled glucose profile by continuous glucose monitoring: A prospective cohort study. Diabetes Res Clin Pract. 2022;189:109940 (Jun 1). Doi: 10.1016/j.diabres.2022.109940

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Key clinical point: Greater glycemic variability measured as the coefficient of variation for glucose (%CV) level was associated with a higher risk for all-cause mortality in patients with type 2 diabetes (T2D) and a well-controlled glucose status.

 

Major finding: Compared with patients with a %CV level of ≤20%, those with a %CV level of 20%-25% (adjusted HR [aHR] 1.16; 95% CI 0.78-1.73), 25%-30% (aHR 1.38; 95% CI 0.89-2.15), 30%-35% (aHR 1.33; 95% CI 0.77-2.29), and >35% (aHR 2.26; 95% CI 1.13-4.52) had a higher risk for all-cause mortality.

 

Study details: This study was a part of the INDIGO study including 1839 patients with T2D who reached continuous glucose monitoring glycemic targets and were classified into five groups by %CV level.

 

Disclosures: This study was supported by the National Key R&D Program of China, the National Natural Science Foundation of China, and others. The authors declared no conflicts of interest.

 

Source: Mo Y et al. Impact of short-term glycemic variability on risk of all-cause mortality in type 2 diabetes patients with well-controlled glucose profile by continuous glucose monitoring: A prospective cohort study. Diabetes Res Clin Pract. 2022;189:109940 (Jun 1). Doi: 10.1016/j.diabres.2022.109940

Key clinical point: Greater glycemic variability measured as the coefficient of variation for glucose (%CV) level was associated with a higher risk for all-cause mortality in patients with type 2 diabetes (T2D) and a well-controlled glucose status.

 

Major finding: Compared with patients with a %CV level of ≤20%, those with a %CV level of 20%-25% (adjusted HR [aHR] 1.16; 95% CI 0.78-1.73), 25%-30% (aHR 1.38; 95% CI 0.89-2.15), 30%-35% (aHR 1.33; 95% CI 0.77-2.29), and >35% (aHR 2.26; 95% CI 1.13-4.52) had a higher risk for all-cause mortality.

 

Study details: This study was a part of the INDIGO study including 1839 patients with T2D who reached continuous glucose monitoring glycemic targets and were classified into five groups by %CV level.

 

Disclosures: This study was supported by the National Key R&D Program of China, the National Natural Science Foundation of China, and others. The authors declared no conflicts of interest.

 

Source: Mo Y et al. Impact of short-term glycemic variability on risk of all-cause mortality in type 2 diabetes patients with well-controlled glucose profile by continuous glucose monitoring: A prospective cohort study. Diabetes Res Clin Pract. 2022;189:109940 (Jun 1). Doi: 10.1016/j.diabres.2022.109940

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T2D: Noninferior efficacy with adding low-dose vs. standard-dose lobeglitazone to metformin and DPP4i

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Key clinical point: Addition of low-dose (0.25 mg/day) vs. standard-dose (0.5 mg/day) lobeglitazone to metformin plus dipeptidyl peptidase 4 inhibitor (DPP4i) therapy led to noninferior glucose lowering effects and fewer adverse outcomes in patients with type 2 diabetes mellitus (T2D).

 

Major finding: At week 24, the mean glycated hemoglobin level in the low-dose vs. standard-dose lobeglitazone group was 6.87% ± 0.54% vs. 6.68% ±0 .46%, respectively, with a between-group difference of 0.18% (95% Cl 0.017%-0.345%) showing noninferiority of the low-dose to standard-dose treatment. Treatment-emergent adverse events were more frequent in the standard-dose vs. low-dose group.

 

Study details: This was a phase 4 study including 134 patients with T2D inadequately controlled on metformin plus DPP4i therapy who were randomly assigned to receive low-dose (n = 67) or standard-dose (n = 67) lobeglitazone.

 

Disclosures: This study was supported by a research grant from Chong Kun Dang Pharmaceutical

Corporation, Seoul, Republic of Korea.

 

Source: Ryang S et al. A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study. Diabetes Obes Metab. 2022 (May 17). Doi: 10.1111/dom.14766.

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Key clinical point: Addition of low-dose (0.25 mg/day) vs. standard-dose (0.5 mg/day) lobeglitazone to metformin plus dipeptidyl peptidase 4 inhibitor (DPP4i) therapy led to noninferior glucose lowering effects and fewer adverse outcomes in patients with type 2 diabetes mellitus (T2D).

 

Major finding: At week 24, the mean glycated hemoglobin level in the low-dose vs. standard-dose lobeglitazone group was 6.87% ± 0.54% vs. 6.68% ±0 .46%, respectively, with a between-group difference of 0.18% (95% Cl 0.017%-0.345%) showing noninferiority of the low-dose to standard-dose treatment. Treatment-emergent adverse events were more frequent in the standard-dose vs. low-dose group.

 

Study details: This was a phase 4 study including 134 patients with T2D inadequately controlled on metformin plus DPP4i therapy who were randomly assigned to receive low-dose (n = 67) or standard-dose (n = 67) lobeglitazone.

 

Disclosures: This study was supported by a research grant from Chong Kun Dang Pharmaceutical

Corporation, Seoul, Republic of Korea.

 

Source: Ryang S et al. A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study. Diabetes Obes Metab. 2022 (May 17). Doi: 10.1111/dom.14766.

Key clinical point: Addition of low-dose (0.25 mg/day) vs. standard-dose (0.5 mg/day) lobeglitazone to metformin plus dipeptidyl peptidase 4 inhibitor (DPP4i) therapy led to noninferior glucose lowering effects and fewer adverse outcomes in patients with type 2 diabetes mellitus (T2D).

 

Major finding: At week 24, the mean glycated hemoglobin level in the low-dose vs. standard-dose lobeglitazone group was 6.87% ± 0.54% vs. 6.68% ±0 .46%, respectively, with a between-group difference of 0.18% (95% Cl 0.017%-0.345%) showing noninferiority of the low-dose to standard-dose treatment. Treatment-emergent adverse events were more frequent in the standard-dose vs. low-dose group.

 

Study details: This was a phase 4 study including 134 patients with T2D inadequately controlled on metformin plus DPP4i therapy who were randomly assigned to receive low-dose (n = 67) or standard-dose (n = 67) lobeglitazone.

 

Disclosures: This study was supported by a research grant from Chong Kun Dang Pharmaceutical

Corporation, Seoul, Republic of Korea.

 

Source: Ryang S et al. A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study. Diabetes Obes Metab. 2022 (May 17). Doi: 10.1111/dom.14766.

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Obesity may be protective against diabetic retinopathy in T2D

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Key clinical point: Obesity appeared to be a protective factor for the development of diabetic macular edema (DME) and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes mellitus (T2D), whereas the waist-to-height ratio appeared to be a significant risk factor.

 

Major finding: Obesity was associated with a lower risk for DME (adjusted odds ratio [aOR] 0.40; P = .041) and VTDR (aOR 0.37; P = .023), whereas a higher waist-to-height ratio was associated with a higher risk for DME (aOR 3.04; P = .041) and VTDR (aOR 2.74; P = .048), with all associations being more significant in women.

 

Study details: Findings are from an ongoing prospective study that included 2305 patients with T2D.

 

Disclosures: This study was supported by the National Natural Science Foundation of China and Guangzhou Science & Technology Plan of Guangdong Pearl River Talents Program. No competing interests were declared.

 

Source: Li W et al. Association of different kinds of obesity with diabetic retinopathy in patients with type 2 diabetes. BMJ Open. 2023;12:e056332 (May 19). Doi: 10.1136/bmjopen-2021-056332

 

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Key clinical point: Obesity appeared to be a protective factor for the development of diabetic macular edema (DME) and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes mellitus (T2D), whereas the waist-to-height ratio appeared to be a significant risk factor.

 

Major finding: Obesity was associated with a lower risk for DME (adjusted odds ratio [aOR] 0.40; P = .041) and VTDR (aOR 0.37; P = .023), whereas a higher waist-to-height ratio was associated with a higher risk for DME (aOR 3.04; P = .041) and VTDR (aOR 2.74; P = .048), with all associations being more significant in women.

 

Study details: Findings are from an ongoing prospective study that included 2305 patients with T2D.

 

Disclosures: This study was supported by the National Natural Science Foundation of China and Guangzhou Science & Technology Plan of Guangdong Pearl River Talents Program. No competing interests were declared.

 

Source: Li W et al. Association of different kinds of obesity with diabetic retinopathy in patients with type 2 diabetes. BMJ Open. 2023;12:e056332 (May 19). Doi: 10.1136/bmjopen-2021-056332

 

Key clinical point: Obesity appeared to be a protective factor for the development of diabetic macular edema (DME) and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes mellitus (T2D), whereas the waist-to-height ratio appeared to be a significant risk factor.

 

Major finding: Obesity was associated with a lower risk for DME (adjusted odds ratio [aOR] 0.40; P = .041) and VTDR (aOR 0.37; P = .023), whereas a higher waist-to-height ratio was associated with a higher risk for DME (aOR 3.04; P = .041) and VTDR (aOR 2.74; P = .048), with all associations being more significant in women.

 

Study details: Findings are from an ongoing prospective study that included 2305 patients with T2D.

 

Disclosures: This study was supported by the National Natural Science Foundation of China and Guangzhou Science & Technology Plan of Guangdong Pearl River Talents Program. No competing interests were declared.

 

Source: Li W et al. Association of different kinds of obesity with diabetic retinopathy in patients with type 2 diabetes. BMJ Open. 2023;12:e056332 (May 19). Doi: 10.1136/bmjopen-2021-056332

 

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Insights on comparative efficacy of tirzepatide and semaglutide in T2D

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Key clinical point: Tirzepatide. at doses of  10 or 15 mg, vs. 2 mg semaglutide was associated with a significantly greater reduction in glycated hemoglobin (A1c) levels and body weight in patients with type 2 diabetes (T2D). Both drugs had a similar overall safety profile.

 

Major finding: At week 40, 10 and 15 mg tirzepatide vs. 2 mg semaglutide led to a significantly greater reduction in A1c levels (estimated treatment difference [ETD] 0.36%; P = .008, and ETD 0.4%; P = .003, respectively) and body weight (ETD 3.15 and 5.15 kg, respectively; both P < .001).

 

Study details: This was an adjusted indirect treatment comparison study that included patients with T2D from the SURPASS-2 (n = 1879) and SUSTAIN FORTE (n = 961) trials who were randomly assigned to receive tirzepatide or injectable semaglutide.

 

Disclosures: This study was funded by Eli Lilly and Company. Two authors declared being advisory board members or receiving speaking or consulting honoraria or research support from various sources, including Eli Lilly. The other authors are employees and shareholders of Eli Lilly.

 

Source: Vadher K et al. Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison. Diabetes Obes Metab. 2022 (May 19). Doi: 10.1111/dom.14775

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Key clinical point: Tirzepatide. at doses of  10 or 15 mg, vs. 2 mg semaglutide was associated with a significantly greater reduction in glycated hemoglobin (A1c) levels and body weight in patients with type 2 diabetes (T2D). Both drugs had a similar overall safety profile.

 

Major finding: At week 40, 10 and 15 mg tirzepatide vs. 2 mg semaglutide led to a significantly greater reduction in A1c levels (estimated treatment difference [ETD] 0.36%; P = .008, and ETD 0.4%; P = .003, respectively) and body weight (ETD 3.15 and 5.15 kg, respectively; both P < .001).

 

Study details: This was an adjusted indirect treatment comparison study that included patients with T2D from the SURPASS-2 (n = 1879) and SUSTAIN FORTE (n = 961) trials who were randomly assigned to receive tirzepatide or injectable semaglutide.

 

Disclosures: This study was funded by Eli Lilly and Company. Two authors declared being advisory board members or receiving speaking or consulting honoraria or research support from various sources, including Eli Lilly. The other authors are employees and shareholders of Eli Lilly.

 

Source: Vadher K et al. Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison. Diabetes Obes Metab. 2022 (May 19). Doi: 10.1111/dom.14775

Key clinical point: Tirzepatide. at doses of  10 or 15 mg, vs. 2 mg semaglutide was associated with a significantly greater reduction in glycated hemoglobin (A1c) levels and body weight in patients with type 2 diabetes (T2D). Both drugs had a similar overall safety profile.

 

Major finding: At week 40, 10 and 15 mg tirzepatide vs. 2 mg semaglutide led to a significantly greater reduction in A1c levels (estimated treatment difference [ETD] 0.36%; P = .008, and ETD 0.4%; P = .003, respectively) and body weight (ETD 3.15 and 5.15 kg, respectively; both P < .001).

 

Study details: This was an adjusted indirect treatment comparison study that included patients with T2D from the SURPASS-2 (n = 1879) and SUSTAIN FORTE (n = 961) trials who were randomly assigned to receive tirzepatide or injectable semaglutide.

 

Disclosures: This study was funded by Eli Lilly and Company. Two authors declared being advisory board members or receiving speaking or consulting honoraria or research support from various sources, including Eli Lilly. The other authors are employees and shareholders of Eli Lilly.

 

Source: Vadher K et al. Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison. Diabetes Obes Metab. 2022 (May 19). Doi: 10.1111/dom.14775

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T2D: Meta-analysis suggests superiority of tirzepatide over other glucose lowering therapies

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Key clinical point: In patients with type 2 diabetes (T2D), once-weekly tirzepatide demonstrated dose-dependent superiority on glycemic efficacy vs. placebo, long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), and basal insulin, without increasing the chances of hypoglycemia.

 

Major finding: Tirzepatide, at does of 5, 10, and 15 mg, was more effective than placebo in reducing glycated hemoglobin levels, with mean differences (95% CI) being −17.71 (−21.66 to −13.75), −20.20 (−22.90 to −17.51), and −22.35 (−26.09 to −18.62) mmol/mol, respectively. Similar findings were recorded for tirzepatide vs. GLP-1 RA or basal insulin. The incidence of hypoglycemia was not significantly different between the treatment groups.

 

Study details: The data come from a meta-analysis of seven randomized controlled trials including 6609 patients with T2D.

 

Disclosures: The study received no specific funding. Some authors declared receiving research grants, consulting fees, research support, or honoraria from, or serving as consultants or advisory board members for various sources.

 

Source: Karagiannis T et al. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: A systematic review and meta-analysis. Diabetologia. 2022 (May 17). Doi: 10.1007/s00125-022-05715-4

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Key clinical point: In patients with type 2 diabetes (T2D), once-weekly tirzepatide demonstrated dose-dependent superiority on glycemic efficacy vs. placebo, long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), and basal insulin, without increasing the chances of hypoglycemia.

 

Major finding: Tirzepatide, at does of 5, 10, and 15 mg, was more effective than placebo in reducing glycated hemoglobin levels, with mean differences (95% CI) being −17.71 (−21.66 to −13.75), −20.20 (−22.90 to −17.51), and −22.35 (−26.09 to −18.62) mmol/mol, respectively. Similar findings were recorded for tirzepatide vs. GLP-1 RA or basal insulin. The incidence of hypoglycemia was not significantly different between the treatment groups.

 

Study details: The data come from a meta-analysis of seven randomized controlled trials including 6609 patients with T2D.

 

Disclosures: The study received no specific funding. Some authors declared receiving research grants, consulting fees, research support, or honoraria from, or serving as consultants or advisory board members for various sources.

 

Source: Karagiannis T et al. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: A systematic review and meta-analysis. Diabetologia. 2022 (May 17). Doi: 10.1007/s00125-022-05715-4

Key clinical point: In patients with type 2 diabetes (T2D), once-weekly tirzepatide demonstrated dose-dependent superiority on glycemic efficacy vs. placebo, long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), and basal insulin, without increasing the chances of hypoglycemia.

 

Major finding: Tirzepatide, at does of 5, 10, and 15 mg, was more effective than placebo in reducing glycated hemoglobin levels, with mean differences (95% CI) being −17.71 (−21.66 to −13.75), −20.20 (−22.90 to −17.51), and −22.35 (−26.09 to −18.62) mmol/mol, respectively. Similar findings were recorded for tirzepatide vs. GLP-1 RA or basal insulin. The incidence of hypoglycemia was not significantly different between the treatment groups.

 

Study details: The data come from a meta-analysis of seven randomized controlled trials including 6609 patients with T2D.

 

Disclosures: The study received no specific funding. Some authors declared receiving research grants, consulting fees, research support, or honoraria from, or serving as consultants or advisory board members for various sources.

 

Source: Karagiannis T et al. Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: A systematic review and meta-analysis. Diabetologia. 2022 (May 17). Doi: 10.1007/s00125-022-05715-4

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OGTT prognostic for T2D risk in nulliparous pregnant women testing negative for GD

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Key clinical point: The antepartum 75g-oral glucose tolerance test (75g-OGTT) can identify nulliparous pregnant women who are at risk of developing type 2 diabetes mellitus (T2D), even if they tested negative for gestational diabetes (GD).

 

Major finding: In women without GD, the fasting (adjusted hazard ratio [aHR] 2.82; 95% CI 2.18-3.64), 1-hour (aHR 1.26; 95% CI 1.15-1.37), and 2-hour (aHR 1.14; 95% CI 1.04-1.25) 75g-OGTT values were significantly associated with a future risk of developing T2D, with a model combining all three OGTT values and clinical characteristics being able to detect 43.7% (95% CI 43.2%-44.2%) of women who developed T2D at 5 years after the index pregnancy.

 

Study details: The data come from a retrospective study of 41,507 nulliparous pregnant women who tested negative for GD using a 75g-OGTT.

 

Disclosures: This study was funded by the Canadian Institute of Health Research. The authors report no conflicts of interest.

 

Source: Hiersch L et al. The prognostic value of the oral glucose tolerance test for future type-2 diabetes in nulliparous pregnant women testing negative for gestational diabetes. Diabetes Metab. 2022 (Jun 2). Doi: 10.1016/j.diabet.2022.101364

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Key clinical point: The antepartum 75g-oral glucose tolerance test (75g-OGTT) can identify nulliparous pregnant women who are at risk of developing type 2 diabetes mellitus (T2D), even if they tested negative for gestational diabetes (GD).

 

Major finding: In women without GD, the fasting (adjusted hazard ratio [aHR] 2.82; 95% CI 2.18-3.64), 1-hour (aHR 1.26; 95% CI 1.15-1.37), and 2-hour (aHR 1.14; 95% CI 1.04-1.25) 75g-OGTT values were significantly associated with a future risk of developing T2D, with a model combining all three OGTT values and clinical characteristics being able to detect 43.7% (95% CI 43.2%-44.2%) of women who developed T2D at 5 years after the index pregnancy.

 

Study details: The data come from a retrospective study of 41,507 nulliparous pregnant women who tested negative for GD using a 75g-OGTT.

 

Disclosures: This study was funded by the Canadian Institute of Health Research. The authors report no conflicts of interest.

 

Source: Hiersch L et al. The prognostic value of the oral glucose tolerance test for future type-2 diabetes in nulliparous pregnant women testing negative for gestational diabetes. Diabetes Metab. 2022 (Jun 2). Doi: 10.1016/j.diabet.2022.101364

Key clinical point: The antepartum 75g-oral glucose tolerance test (75g-OGTT) can identify nulliparous pregnant women who are at risk of developing type 2 diabetes mellitus (T2D), even if they tested negative for gestational diabetes (GD).

 

Major finding: In women without GD, the fasting (adjusted hazard ratio [aHR] 2.82; 95% CI 2.18-3.64), 1-hour (aHR 1.26; 95% CI 1.15-1.37), and 2-hour (aHR 1.14; 95% CI 1.04-1.25) 75g-OGTT values were significantly associated with a future risk of developing T2D, with a model combining all three OGTT values and clinical characteristics being able to detect 43.7% (95% CI 43.2%-44.2%) of women who developed T2D at 5 years after the index pregnancy.

 

Study details: The data come from a retrospective study of 41,507 nulliparous pregnant women who tested negative for GD using a 75g-OGTT.

 

Disclosures: This study was funded by the Canadian Institute of Health Research. The authors report no conflicts of interest.

 

Source: Hiersch L et al. The prognostic value of the oral glucose tolerance test for future type-2 diabetes in nulliparous pregnant women testing negative for gestational diabetes. Diabetes Metab. 2022 (Jun 2). Doi: 10.1016/j.diabet.2022.101364

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Metformin combination therapy tops metformin monotherapy in untreated T2D

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Key clinical point: Combination of metformin plus a low hypoglycemic risk antidiabetic drug provides better glycemic control than metformin monotherapy without increasing the risk for hypoglycemia in patients with untreated type 2 diabetes mellitus (T2D).

 

Major finding: Combination therapy vs. metformin monotherapy significantly reduced glycated hemoglobin (A1c) levels (mean difference [MD] 0.48%; P < .001) and fasting plasma glucose levels (MD 0.92 mmol/L; P < .001) and led to a higher proportion of patients achieving  an A1c level of <7% (odds ratio 2.21; P < .00001), without any significant increase in hypoglycemic events.

 

Study details: Findings are from a meta-analysis of 14 randomized controlled trials including 5316 patients with untreated T2D who were randomly assigned to receive combination therapy or metformin monotherapy.

 

Disclosures: This work was supported by Ministry of Science and Technology and Chang Gung Memorial Hospital, Taiwan. The authors declared no conflicts of interest.

 

Source: Hung WT et al. Metformin plus a low hypoglycemic risk antidiabetic drug vs. metformin monotherapy for untreated type 2 diabetes mellitus: A meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2022;189:10937 (Jun 1). Doi: 10.1016/j.diabres.2022.109937

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Key clinical point: Combination of metformin plus a low hypoglycemic risk antidiabetic drug provides better glycemic control than metformin monotherapy without increasing the risk for hypoglycemia in patients with untreated type 2 diabetes mellitus (T2D).

 

Major finding: Combination therapy vs. metformin monotherapy significantly reduced glycated hemoglobin (A1c) levels (mean difference [MD] 0.48%; P < .001) and fasting plasma glucose levels (MD 0.92 mmol/L; P < .001) and led to a higher proportion of patients achieving  an A1c level of <7% (odds ratio 2.21; P < .00001), without any significant increase in hypoglycemic events.

 

Study details: Findings are from a meta-analysis of 14 randomized controlled trials including 5316 patients with untreated T2D who were randomly assigned to receive combination therapy or metformin monotherapy.

 

Disclosures: This work was supported by Ministry of Science and Technology and Chang Gung Memorial Hospital, Taiwan. The authors declared no conflicts of interest.

 

Source: Hung WT et al. Metformin plus a low hypoglycemic risk antidiabetic drug vs. metformin monotherapy for untreated type 2 diabetes mellitus: A meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2022;189:10937 (Jun 1). Doi: 10.1016/j.diabres.2022.109937

Key clinical point: Combination of metformin plus a low hypoglycemic risk antidiabetic drug provides better glycemic control than metformin monotherapy without increasing the risk for hypoglycemia in patients with untreated type 2 diabetes mellitus (T2D).

 

Major finding: Combination therapy vs. metformin monotherapy significantly reduced glycated hemoglobin (A1c) levels (mean difference [MD] 0.48%; P < .001) and fasting plasma glucose levels (MD 0.92 mmol/L; P < .001) and led to a higher proportion of patients achieving  an A1c level of <7% (odds ratio 2.21; P < .00001), without any significant increase in hypoglycemic events.

 

Study details: Findings are from a meta-analysis of 14 randomized controlled trials including 5316 patients with untreated T2D who were randomly assigned to receive combination therapy or metformin monotherapy.

 

Disclosures: This work was supported by Ministry of Science and Technology and Chang Gung Memorial Hospital, Taiwan. The authors declared no conflicts of interest.

 

Source: Hung WT et al. Metformin plus a low hypoglycemic risk antidiabetic drug vs. metformin monotherapy for untreated type 2 diabetes mellitus: A meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2022;189:10937 (Jun 1). Doi: 10.1016/j.diabres.2022.109937

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T2D: Cardiovascular and safety outcomes associated first-line SGLT-2i vs. metformin

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Key clinical point: Patients with type 2 diabetes (T2D) who initiated first-line sodium-glucose cotransporter-2 inhibitors (SGLT-2i) vs. metformin showed a similar risk for hospitalization for myocardial infarction (MI)/stroke or all-cause mortality, a lower risk for hospitalization for heart failure (HHF) or all-cause mortality, and a similar safety profile, except for an increased risk for genital infections.

 

Major finding: Patients initiating the first-line treatment with SGLT-2i vs. metformin had a similar risk for MI/stroke/mortality (hazard ratio[HR] 0.96; 95% CI 0.77-1.19), a lower risk for HHF/mortality (HR 0.80; 95% CI 0.66-0.97), and a similar safety profile, except for an increased risk for genital infections (HR 2.19; 95% CI 1.91-2.51).

 

Study details: This population-based cohort study included 8613 patients with T2D initiating SGLT-2i and 17,226 matched patients initiating metformin.

 

Disclosures: This study was funded by the Brigham and Women's Hospital and Harvard Medical School. RJ Glynn, E Patorno, and S Schneeweiss declared receiving research grants or consulting fees, serving on advisory boards, or holding stock or stock options for various sources.

 

Source: Shin H et al. Cardiovascular outcomes in patients initiating first-line treatment of type 2 diabetes with sodium–glucose cotransporter-2 inhibitors versus metformin: A cohort study. Ann Intern Med. 2022 (May 24). Doi: 10.7326/M21-4012

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Key clinical point: Patients with type 2 diabetes (T2D) who initiated first-line sodium-glucose cotransporter-2 inhibitors (SGLT-2i) vs. metformin showed a similar risk for hospitalization for myocardial infarction (MI)/stroke or all-cause mortality, a lower risk for hospitalization for heart failure (HHF) or all-cause mortality, and a similar safety profile, except for an increased risk for genital infections.

 

Major finding: Patients initiating the first-line treatment with SGLT-2i vs. metformin had a similar risk for MI/stroke/mortality (hazard ratio[HR] 0.96; 95% CI 0.77-1.19), a lower risk for HHF/mortality (HR 0.80; 95% CI 0.66-0.97), and a similar safety profile, except for an increased risk for genital infections (HR 2.19; 95% CI 1.91-2.51).

 

Study details: This population-based cohort study included 8613 patients with T2D initiating SGLT-2i and 17,226 matched patients initiating metformin.

 

Disclosures: This study was funded by the Brigham and Women's Hospital and Harvard Medical School. RJ Glynn, E Patorno, and S Schneeweiss declared receiving research grants or consulting fees, serving on advisory boards, or holding stock or stock options for various sources.

 

Source: Shin H et al. Cardiovascular outcomes in patients initiating first-line treatment of type 2 diabetes with sodium–glucose cotransporter-2 inhibitors versus metformin: A cohort study. Ann Intern Med. 2022 (May 24). Doi: 10.7326/M21-4012

Key clinical point: Patients with type 2 diabetes (T2D) who initiated first-line sodium-glucose cotransporter-2 inhibitors (SGLT-2i) vs. metformin showed a similar risk for hospitalization for myocardial infarction (MI)/stroke or all-cause mortality, a lower risk for hospitalization for heart failure (HHF) or all-cause mortality, and a similar safety profile, except for an increased risk for genital infections.

 

Major finding: Patients initiating the first-line treatment with SGLT-2i vs. metformin had a similar risk for MI/stroke/mortality (hazard ratio[HR] 0.96; 95% CI 0.77-1.19), a lower risk for HHF/mortality (HR 0.80; 95% CI 0.66-0.97), and a similar safety profile, except for an increased risk for genital infections (HR 2.19; 95% CI 1.91-2.51).

 

Study details: This population-based cohort study included 8613 patients with T2D initiating SGLT-2i and 17,226 matched patients initiating metformin.

 

Disclosures: This study was funded by the Brigham and Women's Hospital and Harvard Medical School. RJ Glynn, E Patorno, and S Schneeweiss declared receiving research grants or consulting fees, serving on advisory boards, or holding stock or stock options for various sources.

 

Source: Shin H et al. Cardiovascular outcomes in patients initiating first-line treatment of type 2 diabetes with sodium–glucose cotransporter-2 inhibitors versus metformin: A cohort study. Ann Intern Med. 2022 (May 24). Doi: 10.7326/M21-4012

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Once-weekly dulaglutide improves glycemic control in youths with T2D

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Key clinical point: Once-weekly dulaglutide was superior to placebo in improving glycemic control through 26 weeks in youths with inadequately controlled type 2 diabetes (T2D) who were being treated with or without metformin or basal insulin.

 

Major finding: At 26 weeks, 0.75 mg and 1.5 mg dulaglutide vs. placebo led to a significant reduction in mean glycated hemoglobin (A1c) level (estimated treatment difference 1.2% and 1.5%, respectively), in addition to a significant increase in the proportion of patients achieving an A1c level of <7.0% (all P < .001) and a consistent safety profile.

 

Study details: The data come from the AWARD-PEDS trial including 154 patients with T2D treated with lifestyle modification alone or metformin with or without basal insulin and who were randomly assigned to receive once-weekly dulaglutide or placebo for 26 weeks.

 

Disclosures: This study was funded by Eli Lilly and Company. Some authors declared receiving grants or contracts or serving as consultants or on safety and data monitoring boards for various sources, including Eli Lilly. D Cox declared being an employee of and holding stocks or stock options in Eli Lilly.

 

Source: Arslanian SA et al. Once-weekly dulaglutide for the treatment of youths with type 2 diabetes. N Engl J Med. 2022 (Jun 4). Doi: 10.1056/NEJMoa2204601

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Key clinical point: Once-weekly dulaglutide was superior to placebo in improving glycemic control through 26 weeks in youths with inadequately controlled type 2 diabetes (T2D) who were being treated with or without metformin or basal insulin.

 

Major finding: At 26 weeks, 0.75 mg and 1.5 mg dulaglutide vs. placebo led to a significant reduction in mean glycated hemoglobin (A1c) level (estimated treatment difference 1.2% and 1.5%, respectively), in addition to a significant increase in the proportion of patients achieving an A1c level of <7.0% (all P < .001) and a consistent safety profile.

 

Study details: The data come from the AWARD-PEDS trial including 154 patients with T2D treated with lifestyle modification alone or metformin with or without basal insulin and who were randomly assigned to receive once-weekly dulaglutide or placebo for 26 weeks.

 

Disclosures: This study was funded by Eli Lilly and Company. Some authors declared receiving grants or contracts or serving as consultants or on safety and data monitoring boards for various sources, including Eli Lilly. D Cox declared being an employee of and holding stocks or stock options in Eli Lilly.

 

Source: Arslanian SA et al. Once-weekly dulaglutide for the treatment of youths with type 2 diabetes. N Engl J Med. 2022 (Jun 4). Doi: 10.1056/NEJMoa2204601

Key clinical point: Once-weekly dulaglutide was superior to placebo in improving glycemic control through 26 weeks in youths with inadequately controlled type 2 diabetes (T2D) who were being treated with or without metformin or basal insulin.

 

Major finding: At 26 weeks, 0.75 mg and 1.5 mg dulaglutide vs. placebo led to a significant reduction in mean glycated hemoglobin (A1c) level (estimated treatment difference 1.2% and 1.5%, respectively), in addition to a significant increase in the proportion of patients achieving an A1c level of <7.0% (all P < .001) and a consistent safety profile.

 

Study details: The data come from the AWARD-PEDS trial including 154 patients with T2D treated with lifestyle modification alone or metformin with or without basal insulin and who were randomly assigned to receive once-weekly dulaglutide or placebo for 26 weeks.

 

Disclosures: This study was funded by Eli Lilly and Company. Some authors declared receiving grants or contracts or serving as consultants or on safety and data monitoring boards for various sources, including Eli Lilly. D Cox declared being an employee of and holding stocks or stock options in Eli Lilly.

 

Source: Arslanian SA et al. Once-weekly dulaglutide for the treatment of youths with type 2 diabetes. N Engl J Med. 2022 (Jun 4). Doi: 10.1056/NEJMoa2204601

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Could a type 2 diabetes drug tackle kidney stones?

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Patients with type 2 diabetes who received empagliflozin, a sodium glucose cotransporter-2 (SGLT2) inhibitor, were almost 40% less likely to have a kidney stone than patients who received placebo during a median 1.5 years of treatment.

These findings are from an analysis of pooled data from phase 1-4 clinical trials of empagliflozin for blood glucose control in 15,081 patients with type 2 diabetes.  

Priyadarshini Balasubramanian, MD, presented the study as a poster at the annual meeting of the Endocrine Society; the study also was published online in the Journal of Clinical Endocrinology & Metabolism.

The researchers acknowledge this was a retrospective, post-hoc analysis and that urolithiasis – a stone in the urinary tract, which includes nephrolithiasis, a kidney stone – was an adverse event, not a primary or secondary outcome.

Also, the stone composition, which might help explain how the drug may affect stone formation, is unknown.

Therefore, “dedicated randomized prospective clinical trials are needed to confirm these initial observations in patients both with and without type 2 diabetes,” said Dr. Balasubramanian, a clinical fellow in the section of endocrinology & metabolism, department of internal medicine at Yale University, New Haven, Conn.

However, “if this association is proven, empagliflozin may be used to decrease the risk of kidney stones at least in those with type 2 diabetes, but maybe also in those without diabetes,” Dr. Balasubramanian said in an interview.

Further trials are also needed to determine if this is a class effect, which is likely, she speculated, and to unravel the potential mechanism.

This is important because of the prevalence of kidney stones, which affect up to 15% of the general population and 15%-20% of patients with diabetes, she explained.
 

‘Provocative’ earlier findings

The current study was prompted by a recent observational study by Kasper B. Kristensen, MD, PhD, and colleagues.

Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies “may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.” 

Using data from Danish Health registries, they matched 12,325 individuals newly prescribed an SGLT2 inhibitor 1:1 with patients newly prescribed a glucagonlike peptide-1 (GLP1) agonist, another new class of drugs for treating type 2 diabetes.

They found a hazard ratio of 0.51 (95% confidence interval, 0.37-0.71) for incident nephrolithiasis and a hazard ratio of 0.68 (95% CI, 0.48-0.97) for recurrent nephrolithiasis for patients taking SGLT2 inhibitors versus GLP-1 agonists.

These findings are “striking,” according to Dr. Balasubramanian and colleagues. However, “these data, while provocative, were entirely retrospective and therefore possibly prone to bias,” they add.
 

Pooled data from 20 trials

The current study analyzed data from 20 randomized controlled trials of glycemic control in type 2 diabetes, in which 10,177 patients had received empagliflozin 10 mg or 25 mg and 4,904 patients had received placebo.

Most patients (46.5%) had participated in the EMPA-REG OUTCOMES trial, which also had the longest follow-up (2.6 years).

The researchers identified patients with a new stone from the urinary tract (including the kidney, ureter, and urethra). Patients had received either the study drug for a median of 543 days or placebo for a median of 549 days.

During treatment, 104 of 10,177 patients in the pooled empagliflozin groups and 79 of 4,904 patients in the pooled placebo groups developed a stone in the urinary tract.

This was equivalent to 0.63 new urinary-tract stones per 100 patient-years in the pooled empagliflozin groups versus 1.01 new urinary-tract stones per 100 patient-years in the pooled placebo groups.

The incidence rate ratio was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin.

When the analysis was restricted to new kidney stones, the results were similar: 75 of 10,177 patients in the pooled empagliflozin groups and 57 of 4,904 patients in the pooled placebo groups developed a kidney stone.

This was equivalent to 0.45 new kidney stones per 100 patient-years in the pooled empagliflozin groups versus 0.72 new kidney stones per 100 patient-years in the pooled placebo groups.

The IRR was 0.65 (95% CI, 0.46-0.92), in favor of empagliflozin.
 

 

 

Upcoming small RCT in adults without diabetes

Invited to comment on the new study, Dr. Kristensen said: “The reduced risk of SGLT2 inhibitors towards nephrolithiasis is now reported in at least two studies with different methodology, different populations, and different exposure and outcome definitions.”

“I agree that randomized clinical trials designed specifically to confirm these findings appear warranted,” added Dr. Kristensen, from the Institute of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark in Odense.

There is a need for studies in patients with and without diabetes, he added, especially ones that focus on prevention of nephrolithiasis in patients with kidney stone disease.

A new trial should shed further light on this.

Results are expected by the end of 2022 for SWEETSTONE (Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers), a randomized, double-blind crossover exploratory study in 46 patients without diabetes.

This should provide preliminary data to “establish the relevance for larger trials assessing the prophylactic potential of empagliflozin in kidney stone disease,” according to an article on the trial protocol recently published in BMJ.

The trials included in the pooled dataset were funded by Boehringer Ingelheim or the Boehringer Ingelheim and Eli Lilly Diabetes Alliance. Dr. Balasubramanian has reported no relevant financial relationships.

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

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Patients with type 2 diabetes who received empagliflozin, a sodium glucose cotransporter-2 (SGLT2) inhibitor, were almost 40% less likely to have a kidney stone than patients who received placebo during a median 1.5 years of treatment.

These findings are from an analysis of pooled data from phase 1-4 clinical trials of empagliflozin for blood glucose control in 15,081 patients with type 2 diabetes.  

Priyadarshini Balasubramanian, MD, presented the study as a poster at the annual meeting of the Endocrine Society; the study also was published online in the Journal of Clinical Endocrinology & Metabolism.

The researchers acknowledge this was a retrospective, post-hoc analysis and that urolithiasis – a stone in the urinary tract, which includes nephrolithiasis, a kidney stone – was an adverse event, not a primary or secondary outcome.

Also, the stone composition, which might help explain how the drug may affect stone formation, is unknown.

Therefore, “dedicated randomized prospective clinical trials are needed to confirm these initial observations in patients both with and without type 2 diabetes,” said Dr. Balasubramanian, a clinical fellow in the section of endocrinology & metabolism, department of internal medicine at Yale University, New Haven, Conn.

However, “if this association is proven, empagliflozin may be used to decrease the risk of kidney stones at least in those with type 2 diabetes, but maybe also in those without diabetes,” Dr. Balasubramanian said in an interview.

Further trials are also needed to determine if this is a class effect, which is likely, she speculated, and to unravel the potential mechanism.

This is important because of the prevalence of kidney stones, which affect up to 15% of the general population and 15%-20% of patients with diabetes, she explained.
 

‘Provocative’ earlier findings

The current study was prompted by a recent observational study by Kasper B. Kristensen, MD, PhD, and colleagues.

Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies “may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.” 

Using data from Danish Health registries, they matched 12,325 individuals newly prescribed an SGLT2 inhibitor 1:1 with patients newly prescribed a glucagonlike peptide-1 (GLP1) agonist, another new class of drugs for treating type 2 diabetes.

They found a hazard ratio of 0.51 (95% confidence interval, 0.37-0.71) for incident nephrolithiasis and a hazard ratio of 0.68 (95% CI, 0.48-0.97) for recurrent nephrolithiasis for patients taking SGLT2 inhibitors versus GLP-1 agonists.

These findings are “striking,” according to Dr. Balasubramanian and colleagues. However, “these data, while provocative, were entirely retrospective and therefore possibly prone to bias,” they add.
 

Pooled data from 20 trials

The current study analyzed data from 20 randomized controlled trials of glycemic control in type 2 diabetes, in which 10,177 patients had received empagliflozin 10 mg or 25 mg and 4,904 patients had received placebo.

Most patients (46.5%) had participated in the EMPA-REG OUTCOMES trial, which also had the longest follow-up (2.6 years).

The researchers identified patients with a new stone from the urinary tract (including the kidney, ureter, and urethra). Patients had received either the study drug for a median of 543 days or placebo for a median of 549 days.

During treatment, 104 of 10,177 patients in the pooled empagliflozin groups and 79 of 4,904 patients in the pooled placebo groups developed a stone in the urinary tract.

This was equivalent to 0.63 new urinary-tract stones per 100 patient-years in the pooled empagliflozin groups versus 1.01 new urinary-tract stones per 100 patient-years in the pooled placebo groups.

The incidence rate ratio was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin.

When the analysis was restricted to new kidney stones, the results were similar: 75 of 10,177 patients in the pooled empagliflozin groups and 57 of 4,904 patients in the pooled placebo groups developed a kidney stone.

This was equivalent to 0.45 new kidney stones per 100 patient-years in the pooled empagliflozin groups versus 0.72 new kidney stones per 100 patient-years in the pooled placebo groups.

The IRR was 0.65 (95% CI, 0.46-0.92), in favor of empagliflozin.
 

 

 

Upcoming small RCT in adults without diabetes

Invited to comment on the new study, Dr. Kristensen said: “The reduced risk of SGLT2 inhibitors towards nephrolithiasis is now reported in at least two studies with different methodology, different populations, and different exposure and outcome definitions.”

“I agree that randomized clinical trials designed specifically to confirm these findings appear warranted,” added Dr. Kristensen, from the Institute of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark in Odense.

There is a need for studies in patients with and without diabetes, he added, especially ones that focus on prevention of nephrolithiasis in patients with kidney stone disease.

A new trial should shed further light on this.

Results are expected by the end of 2022 for SWEETSTONE (Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers), a randomized, double-blind crossover exploratory study in 46 patients without diabetes.

This should provide preliminary data to “establish the relevance for larger trials assessing the prophylactic potential of empagliflozin in kidney stone disease,” according to an article on the trial protocol recently published in BMJ.

The trials included in the pooled dataset were funded by Boehringer Ingelheim or the Boehringer Ingelheim and Eli Lilly Diabetes Alliance. Dr. Balasubramanian has reported no relevant financial relationships.

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

Patients with type 2 diabetes who received empagliflozin, a sodium glucose cotransporter-2 (SGLT2) inhibitor, were almost 40% less likely to have a kidney stone than patients who received placebo during a median 1.5 years of treatment.

These findings are from an analysis of pooled data from phase 1-4 clinical trials of empagliflozin for blood glucose control in 15,081 patients with type 2 diabetes.  

Priyadarshini Balasubramanian, MD, presented the study as a poster at the annual meeting of the Endocrine Society; the study also was published online in the Journal of Clinical Endocrinology & Metabolism.

The researchers acknowledge this was a retrospective, post-hoc analysis and that urolithiasis – a stone in the urinary tract, which includes nephrolithiasis, a kidney stone – was an adverse event, not a primary or secondary outcome.

Also, the stone composition, which might help explain how the drug may affect stone formation, is unknown.

Therefore, “dedicated randomized prospective clinical trials are needed to confirm these initial observations in patients both with and without type 2 diabetes,” said Dr. Balasubramanian, a clinical fellow in the section of endocrinology & metabolism, department of internal medicine at Yale University, New Haven, Conn.

However, “if this association is proven, empagliflozin may be used to decrease the risk of kidney stones at least in those with type 2 diabetes, but maybe also in those without diabetes,” Dr. Balasubramanian said in an interview.

Further trials are also needed to determine if this is a class effect, which is likely, she speculated, and to unravel the potential mechanism.

This is important because of the prevalence of kidney stones, which affect up to 15% of the general population and 15%-20% of patients with diabetes, she explained.
 

‘Provocative’ earlier findings

The current study was prompted by a recent observational study by Kasper B. Kristensen, MD, PhD, and colleagues.

Because SGLT2 inhibitors increase urinary glucose excretion through reduced renal reabsorption of glucose leading to osmotic diuresis and increased urinary flow, they hypothesized that these therapies “may reduce the risk of upper urinary tract stones (nephrolithiasis) by reducing the concentration of lithogenic substances in urine.” 

Using data from Danish Health registries, they matched 12,325 individuals newly prescribed an SGLT2 inhibitor 1:1 with patients newly prescribed a glucagonlike peptide-1 (GLP1) agonist, another new class of drugs for treating type 2 diabetes.

They found a hazard ratio of 0.51 (95% confidence interval, 0.37-0.71) for incident nephrolithiasis and a hazard ratio of 0.68 (95% CI, 0.48-0.97) for recurrent nephrolithiasis for patients taking SGLT2 inhibitors versus GLP-1 agonists.

These findings are “striking,” according to Dr. Balasubramanian and colleagues. However, “these data, while provocative, were entirely retrospective and therefore possibly prone to bias,” they add.
 

Pooled data from 20 trials

The current study analyzed data from 20 randomized controlled trials of glycemic control in type 2 diabetes, in which 10,177 patients had received empagliflozin 10 mg or 25 mg and 4,904 patients had received placebo.

Most patients (46.5%) had participated in the EMPA-REG OUTCOMES trial, which also had the longest follow-up (2.6 years).

The researchers identified patients with a new stone from the urinary tract (including the kidney, ureter, and urethra). Patients had received either the study drug for a median of 543 days or placebo for a median of 549 days.

During treatment, 104 of 10,177 patients in the pooled empagliflozin groups and 79 of 4,904 patients in the pooled placebo groups developed a stone in the urinary tract.

This was equivalent to 0.63 new urinary-tract stones per 100 patient-years in the pooled empagliflozin groups versus 1.01 new urinary-tract stones per 100 patient-years in the pooled placebo groups.

The incidence rate ratio was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin.

When the analysis was restricted to new kidney stones, the results were similar: 75 of 10,177 patients in the pooled empagliflozin groups and 57 of 4,904 patients in the pooled placebo groups developed a kidney stone.

This was equivalent to 0.45 new kidney stones per 100 patient-years in the pooled empagliflozin groups versus 0.72 new kidney stones per 100 patient-years in the pooled placebo groups.

The IRR was 0.65 (95% CI, 0.46-0.92), in favor of empagliflozin.
 

 

 

Upcoming small RCT in adults without diabetes

Invited to comment on the new study, Dr. Kristensen said: “The reduced risk of SGLT2 inhibitors towards nephrolithiasis is now reported in at least two studies with different methodology, different populations, and different exposure and outcome definitions.”

“I agree that randomized clinical trials designed specifically to confirm these findings appear warranted,” added Dr. Kristensen, from the Institute of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark in Odense.

There is a need for studies in patients with and without diabetes, he added, especially ones that focus on prevention of nephrolithiasis in patients with kidney stone disease.

A new trial should shed further light on this.

Results are expected by the end of 2022 for SWEETSTONE (Impact of the SGLT2 Inhibitor Empagliflozin on Urinary Supersaturations in Kidney Stone Formers), a randomized, double-blind crossover exploratory study in 46 patients without diabetes.

This should provide preliminary data to “establish the relevance for larger trials assessing the prophylactic potential of empagliflozin in kidney stone disease,” according to an article on the trial protocol recently published in BMJ.

The trials included in the pooled dataset were funded by Boehringer Ingelheim or the Boehringer Ingelheim and Eli Lilly Diabetes Alliance. Dr. Balasubramanian has reported no relevant financial relationships.

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

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