Article

Key clinical point: Lower serum bile acid levels (≤2.8 mmol/L) were an independent predictor of progression of diabetic kidney disease (DKD) to end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and biopsy-proven DKD.

Major finding: Overall, 34.78% of patients progressed to ESRD during a median follow-up of 19.02 months, with lower levels of serum bile acids being independently associated with a higher risk for progression to ESRD (adjusted hazard ratio, 5.319; P = .027).

Study details: This was a retrospective cohort study including 184 patients with T2DM and biopsy-proven DKD.

Disclosures: This study was supported by the Health Commission of Sichuan Province Program. The authors declared no conflict of interests.

Source: Xiao X et al. Lower bile acids as an independent risk factor for renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease. Front Endocrinol (Lausanne). 2022;13:1026995  (Oct 7). Doi: 10.3389/fendo.2022.1026995.

Key clinical point: Lower serum bile acid levels (≤2.8 mmol/L) were an independent predictor of progression of diabetic kidney disease (DKD) to end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and biopsy-proven DKD.

Major finding: Overall, 34.78% of patients progressed to ESRD during a median follow-up of 19.02 months, with lower levels of serum bile acids being independently associated with a higher risk for progression to ESRD (adjusted hazard ratio, 5.319; P = .027).

Study details: This was a retrospective cohort study including 184 patients with T2DM and biopsy-proven DKD.

Disclosures: This study was supported by the Health Commission of Sichuan Province Program. The authors declared no conflict of interests.

Source: Xiao X et al. Lower bile acids as an independent risk factor for renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease. Front Endocrinol (Lausanne). 2022;13:1026995  (Oct 7). Doi: 10.3389/fendo.2022.1026995.

Key clinical point: Lower serum bile acid levels (≤2.8 mmol/L) were an independent predictor of progression of diabetic kidney disease (DKD) to end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and biopsy-proven DKD.

Major finding: Overall, 34.78% of patients progressed to ESRD during a median follow-up of 19.02 months, with lower levels of serum bile acids being independently associated with a higher risk for progression to ESRD (adjusted hazard ratio, 5.319; P = .027).

Study details: This was a retrospective cohort study including 184 patients with T2DM and biopsy-proven DKD.

Disclosures: This study was supported by the Health Commission of Sichuan Province Program. The authors declared no conflict of interests.

Source: Xiao X et al. Lower bile acids as an independent risk factor for renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease. Front Endocrinol (Lausanne). 2022;13:1026995  (Oct 7). Doi: 10.3389/fendo.2022.1026995.

Key clinical point: Sodium glucose cotransporter 2 inhibitors (SGLT2i) did not increase the risk for hospitalization for critical limb ischemia (CLI) and lower extremity amputation (LEA) in patients with type 2 diabetes (T2D) compared with glucagon-like peptide-1 receptor agonists (GLP-1RA) or dipeptidyl peptidase-4 inhibitors (DPP4i).

Major finding: SGLT2i was not associated with a higher risk for hospitalization for CLI and LEA compared with either GLP-1RA (hazard ratio [HR] 1.13; 95% CI 0.77-1.65 and HR 1.27; 95% CI 0.63-2.55, respectively) or DPP4i (HR 1.06; 95% CI 0.75-1.50 and HR 0.80; 95% CI 0.42-1.53, respectively).

Study details: Findings are from a population-based retrospective cohort study that propensity score-matched patients with T2D who initiated SGLT2i (n = 13,378) and those who initiated GLP-1RA (n = 13,378).

Disclosures: This study was partly supported by the research grant from National Taiwan University Hospital Yunlin Branch and Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.

Source: Lee YC et al. Risk of major adverse limb events in patients with type 2 diabetes mellitus receiving sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists: A population-based retrospective cohort study. Front Pharmacol. 2022;13:869804  (Sep 13). Doi: 10.3389/fphar.2022.869804

Key clinical point: Sodium glucose cotransporter 2 inhibitors (SGLT2i) did not increase the risk for hospitalization for critical limb ischemia (CLI) and lower extremity amputation (LEA) in patients with type 2 diabetes (T2D) compared with glucagon-like peptide-1 receptor agonists (GLP-1RA) or dipeptidyl peptidase-4 inhibitors (DPP4i).

Major finding: SGLT2i was not associated with a higher risk for hospitalization for CLI and LEA compared with either GLP-1RA (hazard ratio [HR] 1.13; 95% CI 0.77-1.65 and HR 1.27; 95% CI 0.63-2.55, respectively) or DPP4i (HR 1.06; 95% CI 0.75-1.50 and HR 0.80; 95% CI 0.42-1.53, respectively).

Study details: Findings are from a population-based retrospective cohort study that propensity score-matched patients with T2D who initiated SGLT2i (n = 13,378) and those who initiated GLP-1RA (n = 13,378).

Disclosures: This study was partly supported by the research grant from National Taiwan University Hospital Yunlin Branch and Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.

Source: Lee YC et al. Risk of major adverse limb events in patients with type 2 diabetes mellitus receiving sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists: A population-based retrospective cohort study. Front Pharmacol. 2022;13:869804  (Sep 13). Doi: 10.3389/fphar.2022.869804

Key clinical point: Sodium glucose cotransporter 2 inhibitors (SGLT2i) did not increase the risk for hospitalization for critical limb ischemia (CLI) and lower extremity amputation (LEA) in patients with type 2 diabetes (T2D) compared with glucagon-like peptide-1 receptor agonists (GLP-1RA) or dipeptidyl peptidase-4 inhibitors (DPP4i).

Major finding: SGLT2i was not associated with a higher risk for hospitalization for CLI and LEA compared with either GLP-1RA (hazard ratio [HR] 1.13; 95% CI 0.77-1.65 and HR 1.27; 95% CI 0.63-2.55, respectively) or DPP4i (HR 1.06; 95% CI 0.75-1.50 and HR 0.80; 95% CI 0.42-1.53, respectively).

Study details: Findings are from a population-based retrospective cohort study that propensity score-matched patients with T2D who initiated SGLT2i (n = 13,378) and those who initiated GLP-1RA (n = 13,378).

Disclosures: This study was partly supported by the research grant from National Taiwan University Hospital Yunlin Branch and Ministry of Science and Technology, Taiwan. The authors declared no conflicts of interest.

Source: Lee YC et al. Risk of major adverse limb events in patients with type 2 diabetes mellitus receiving sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists: A population-based retrospective cohort study. Front Pharmacol. 2022;13:869804  (Sep 13). Doi: 10.3389/fphar.2022.869804

Key clinical point: Stringent management of blood pressure (BP) with amlodipine in addition to standard diabetes therapy significantly improved glycemic control in patients with type 2 diabetes  (T2D) compared with standard diabetes therapy alone.

Major finding: After 24 weeks, amlodipine plus standard diabetes therapy vs. standard diabetes therapy alone led to a significant reduction in the mean glycated hemoglobin level (6.62% vs 7.01%; P = .01), fasting plasma glucose level (122 vs 129 mg/dL; P < .001), systolic blood pressure (132 vs 143 mm Hg; P < .001), and diastolic blood pressure (78.9 vs 86.0 mm Hg; P < .001), with neural effects on the lipid profile and urinary albumin excretion.

Study details: Findings are from a prospective cohort study including 168 patients with newly diagnosed T2D who received amlodipine plus standard diabetes therapy (n = 87) or standard diabetes therapy alone (n = 81).

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Li JC et al. Antihypertensive treatment improves glycemic control in patients with newly diagnosed type 2 diabetes mellitus: A prospective cohort study. Front Endocrinol (Lausanne). 2022;13:935561  (Sep 9). Doi: 10.3389/fendo.2022.935561.

Key clinical point: Stringent management of blood pressure (BP) with amlodipine in addition to standard diabetes therapy significantly improved glycemic control in patients with type 2 diabetes  (T2D) compared with standard diabetes therapy alone.

Major finding: After 24 weeks, amlodipine plus standard diabetes therapy vs. standard diabetes therapy alone led to a significant reduction in the mean glycated hemoglobin level (6.62% vs 7.01%; P = .01), fasting plasma glucose level (122 vs 129 mg/dL; P < .001), systolic blood pressure (132 vs 143 mm Hg; P < .001), and diastolic blood pressure (78.9 vs 86.0 mm Hg; P < .001), with neural effects on the lipid profile and urinary albumin excretion.

Study details: Findings are from a prospective cohort study including 168 patients with newly diagnosed T2D who received amlodipine plus standard diabetes therapy (n = 87) or standard diabetes therapy alone (n = 81).

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Li JC et al. Antihypertensive treatment improves glycemic control in patients with newly diagnosed type 2 diabetes mellitus: A prospective cohort study. Front Endocrinol (Lausanne). 2022;13:935561  (Sep 9). Doi: 10.3389/fendo.2022.935561.

Key clinical point: Stringent management of blood pressure (BP) with amlodipine in addition to standard diabetes therapy significantly improved glycemic control in patients with type 2 diabetes  (T2D) compared with standard diabetes therapy alone.

Major finding: After 24 weeks, amlodipine plus standard diabetes therapy vs. standard diabetes therapy alone led to a significant reduction in the mean glycated hemoglobin level (6.62% vs 7.01%; P = .01), fasting plasma glucose level (122 vs 129 mg/dL; P < .001), systolic blood pressure (132 vs 143 mm Hg; P < .001), and diastolic blood pressure (78.9 vs 86.0 mm Hg; P < .001), with neural effects on the lipid profile and urinary albumin excretion.

Study details: Findings are from a prospective cohort study including 168 patients with newly diagnosed T2D who received amlodipine plus standard diabetes therapy (n = 87) or standard diabetes therapy alone (n = 81).

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Li JC et al. Antihypertensive treatment improves glycemic control in patients with newly diagnosed type 2 diabetes mellitus: A prospective cohort study. Front Endocrinol (Lausanne). 2022;13:935561  (Sep 9). Doi: 10.3389/fendo.2022.935561.

Key clinical point: Patients with type 2 diabetes mellitus (T2D) receiving metformin vs other antidiabetic drugs or placebo had a higher risk for gastrointestinal (GI) adverse events (AE) such as abdominal pain, nausea, and diarrhea, with the risk for bloating and diarrhea being higher with metformin immediate release (IR) vs extended release (XR).

Major finding: Patients treated with metformin vs. placebo or any other antidiabetic drug were at a significantly higher risk for abdominal pain (risk ratio [RR] 1.491; P = .0001), diarrhea (RR 2.445; P = .0001), and nausea (RR 1.641; P = .0004). The risks for bloating (coefficient −0.89; P = .76) and diarrhea (coefficient −0.344; P = .0437) were higher with metformin IR vs XR.

Study details: The data come from a meta-analysis of 71 randomized controlled trials including 55,042 patients with T2D who were randomly assigned to receive metformin or comparators.

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

Source: Nabrdalik K et al. Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials. Front Endocrinol (Lausanne). 2022;13:975912 (Sep 14). Doi: 10.3389/fendo.2022.975912

Key clinical point: Patients with type 2 diabetes mellitus (T2D) receiving metformin vs other antidiabetic drugs or placebo had a higher risk for gastrointestinal (GI) adverse events (AE) such as abdominal pain, nausea, and diarrhea, with the risk for bloating and diarrhea being higher with metformin immediate release (IR) vs extended release (XR).

Major finding: Patients treated with metformin vs. placebo or any other antidiabetic drug were at a significantly higher risk for abdominal pain (risk ratio [RR] 1.491; P = .0001), diarrhea (RR 2.445; P = .0001), and nausea (RR 1.641; P = .0004). The risks for bloating (coefficient −0.89; P = .76) and diarrhea (coefficient −0.344; P = .0437) were higher with metformin IR vs XR.

Study details: The data come from a meta-analysis of 71 randomized controlled trials including 55,042 patients with T2D who were randomly assigned to receive metformin or comparators.

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

Source: Nabrdalik K et al. Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials. Front Endocrinol (Lausanne). 2022;13:975912 (Sep 14). Doi: 10.3389/fendo.2022.975912

Key clinical point: Patients with type 2 diabetes mellitus (T2D) receiving metformin vs other antidiabetic drugs or placebo had a higher risk for gastrointestinal (GI) adverse events (AE) such as abdominal pain, nausea, and diarrhea, with the risk for bloating and diarrhea being higher with metformin immediate release (IR) vs extended release (XR).

Major finding: Patients treated with metformin vs. placebo or any other antidiabetic drug were at a significantly higher risk for abdominal pain (risk ratio [RR] 1.491; P = .0001), diarrhea (RR 2.445; P = .0001), and nausea (RR 1.641; P = .0004). The risks for bloating (coefficient −0.89; P = .76) and diarrhea (coefficient −0.344; P = .0437) were higher with metformin IR vs XR.

Study details: The data come from a meta-analysis of 71 randomized controlled trials including 55,042 patients with T2D who were randomly assigned to receive metformin or comparators.

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

Source: Nabrdalik K et al. Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials. Front Endocrinol (Lausanne). 2022;13:975912 (Sep 14). Doi: 10.3389/fendo.2022.975912

Key clinical point: Patients with type 2 diabetes (T2D) who used metformin vs. sulfonylurea were at a significantly lower risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VD), but not Parkinson’s disease (PD) or mild cognitive impairment (MCI).

Major finding: The risk for all-cause dementia (hazard ratio [HR] 0.80; 95% CI 0.73-0.88), AD (HR 0.81; 95% CI 0.70-0.94), and VD (HR 0.79; 95% CI 0.63-1.00) was significantly lower in metformin vs sulfonylurea users, with no significant difference in the risk for PD and MCI.

Study details: Findings are from a new user active comparator study including 112,591 patients with T2D, of which 96,140 were new metformin users and 16,451 were new sulfonylurea users.

Disclosures: This study was supported by Janssen Pharmaceuticals. AJ Nevado-Holgado declared receiving funding from Janssen Pharmaceuticals and others. QS Li declared being an employee of Janssen Research & Development, Johnson & Johnson, or holding equity in Johnson & Johnson.

Source: Newby D et al. Comparative effect of metformin versus sulfonylureas with dementia and Parkinson's disease risk in US patients over 50 with type 2 diabetes mellitus. BMJ Open Diabetes Res Care. 2022;10(5):e003036 (Sep 15). Doi: 10.1136/bmjdrc-2022-003036

Key clinical point: Patients with type 2 diabetes (T2D) who used metformin vs. sulfonylurea were at a significantly lower risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VD), but not Parkinson’s disease (PD) or mild cognitive impairment (MCI).

Major finding: The risk for all-cause dementia (hazard ratio [HR] 0.80; 95% CI 0.73-0.88), AD (HR 0.81; 95% CI 0.70-0.94), and VD (HR 0.79; 95% CI 0.63-1.00) was significantly lower in metformin vs sulfonylurea users, with no significant difference in the risk for PD and MCI.

Study details: Findings are from a new user active comparator study including 112,591 patients with T2D, of which 96,140 were new metformin users and 16,451 were new sulfonylurea users.

Disclosures: This study was supported by Janssen Pharmaceuticals. AJ Nevado-Holgado declared receiving funding from Janssen Pharmaceuticals and others. QS Li declared being an employee of Janssen Research & Development, Johnson & Johnson, or holding equity in Johnson & Johnson.

Source: Newby D et al. Comparative effect of metformin versus sulfonylureas with dementia and Parkinson's disease risk in US patients over 50 with type 2 diabetes mellitus. BMJ Open Diabetes Res Care. 2022;10(5):e003036 (Sep 15). Doi: 10.1136/bmjdrc-2022-003036

Key clinical point: Patients with type 2 diabetes (T2D) who used metformin vs. sulfonylurea were at a significantly lower risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VD), but not Parkinson’s disease (PD) or mild cognitive impairment (MCI).

Major finding: The risk for all-cause dementia (hazard ratio [HR] 0.80; 95% CI 0.73-0.88), AD (HR 0.81; 95% CI 0.70-0.94), and VD (HR 0.79; 95% CI 0.63-1.00) was significantly lower in metformin vs sulfonylurea users, with no significant difference in the risk for PD and MCI.

Study details: Findings are from a new user active comparator study including 112,591 patients with T2D, of which 96,140 were new metformin users and 16,451 were new sulfonylurea users.

Disclosures: This study was supported by Janssen Pharmaceuticals. AJ Nevado-Holgado declared receiving funding from Janssen Pharmaceuticals and others. QS Li declared being an employee of Janssen Research & Development, Johnson & Johnson, or holding equity in Johnson & Johnson.

Source: Newby D et al. Comparative effect of metformin versus sulfonylureas with dementia and Parkinson's disease risk in US patients over 50 with type 2 diabetes mellitus. BMJ Open Diabetes Res Care. 2022;10(5):e003036 (Sep 15). Doi: 10.1136/bmjdrc-2022-003036

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.