Type 2 Diabetes ICYMI

Many sodium-glucose cotransporter-2 (SGLT2) inhibitors are approved for use at two doses, but there are few clinical data regarding the metabolic impact of uptitrating an SGLT2 inhibitor from the lower to the higher dose in clinical practice. Matsumura and colleagues published the results of a retrospective, longitudinal study at a single institution in Japan. A total of 52 participants who were treated with 10 mg empagliflozin once daily were analyzed at 26 weeks after the dose had been increased to 25 mg once daily. The researchers reported a 0.6 kg weight reduction, a 0.15% reduction in A1c, and a 22.1 mg/dL reduction in triglycerides in the participants on the higher dose of empagliflozin. Although the benefits of the higher dose were rather small, this study does aid the clinician regarding the clinical impact of increasing the dose of empagliflozin.

Outcome studies with SGLT2 inhibitors have shown reductions in major adverse cardiovascular events (MACE), heart failure hospitalization, and mortality. However, clinicians may be reluctant to initiate SGLT2 inhibitors in frail individuals as they are often excluded from randomized trials and may be more likely to have side effects from this class of medications. Wood and colleagues conducted a cohort study in Australia, comparing the effectiveness of SGLT2 inhibitors to that of dipeptidyl peptidase-4 (DPP-4) inhibitors. The study was done with individuals with type 2 diabetes who were initiated on these agents within 60 days of a hospital discharge. It was noted that SGLT2 inhibitors significantly reduced MACE, heart failure hospitalization, and mortality compared with DPP-4 inhibitors, and this benefit was present in both frail and nonfrail individuals. The study did not report on tolerability issues and is limited by the cohort design, but it does suggest a cardiovascular benefit among frail patients with type 2 diabetes who are treated with SGLT2 inhibitors, and it may be reassuring when considering an SGLT2 inhibitor in a frail person.

In my July 2022 commentary, I discussed the results of AWARD-PEDS, which demonstrated a significant A1c reduction but no weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) dulaglutide in youth with type 2 diabetes. Tamborlane and colleagues have now reported the results of a randomized trial that studied the efficacy and safety of 2 mg exenatide once weekly in youth with type 2 diabetes. Similarly to the AWARD-PEDS study, A1c was significantly reduced compared with placebo, with a difference of -0.85% at 24 weeks. Also similarly to AWARD-PEDS, there was no significant difference in body weight between the GLP-1RA and placebo groups. There are now three studies showing glycemic benefits but little weight loss with GLP-1RA treatment in youth with type 2 diabetes, and while the glycemic benefits are encouraging, it remains perplexing why these studies have not demonstrated the weight loss that has consistently been demonstrated in adult studies of GLP-1RA.

Clinicians often choose a second-generation basal insulin analog (glargine U300, degludec) over a first-generation basal analog (glargine U100, detemir) because of lower rates of hypoglycemia. Randomized clinical trials and real-world evidence (RWE) studies comparing glargine U100 vs degludec have shown somewhat inconsistent results. In the newest RWE study comparing these two second-generation analogs, RESTORE-2 NAIVE, Fadini and colleagues reported that 6 months after initiating either glargine U300 or degludec in insulin-naive type 2 diabetes, there was a similar improvement in glycemia, no weight gain, and low hypoglycemia rates in each group. RESTORE-2 is another study demonstrating similar results between the two second-generation insulin analogs and helps build our understanding that these two insulins are more similar than different.

Many sodium-glucose cotransporter-2 (SGLT2) inhibitors are approved for use at two doses, but there are few clinical data regarding the metabolic impact of uptitrating an SGLT2 inhibitor from the lower to the higher dose in clinical practice. Matsumura and colleagues published the results of a retrospective, longitudinal study at a single institution in Japan. A total of 52 participants who were treated with 10 mg empagliflozin once daily were analyzed at 26 weeks after the dose had been increased to 25 mg once daily. The researchers reported a 0.6 kg weight reduction, a 0.15% reduction in A1c, and a 22.1 mg/dL reduction in triglycerides in the participants on the higher dose of empagliflozin. Although the benefits of the higher dose were rather small, this study does aid the clinician regarding the clinical impact of increasing the dose of empagliflozin.

Outcome studies with SGLT2 inhibitors have shown reductions in major adverse cardiovascular events (MACE), heart failure hospitalization, and mortality. However, clinicians may be reluctant to initiate SGLT2 inhibitors in frail individuals as they are often excluded from randomized trials and may be more likely to have side effects from this class of medications. Wood and colleagues conducted a cohort study in Australia, comparing the effectiveness of SGLT2 inhibitors to that of dipeptidyl peptidase-4 (DPP-4) inhibitors. The study was done with individuals with type 2 diabetes who were initiated on these agents within 60 days of a hospital discharge. It was noted that SGLT2 inhibitors significantly reduced MACE, heart failure hospitalization, and mortality compared with DPP-4 inhibitors, and this benefit was present in both frail and nonfrail individuals. The study did not report on tolerability issues and is limited by the cohort design, but it does suggest a cardiovascular benefit among frail patients with type 2 diabetes who are treated with SGLT2 inhibitors, and it may be reassuring when considering an SGLT2 inhibitor in a frail person.

In my July 2022 commentary, I discussed the results of AWARD-PEDS, which demonstrated a significant A1c reduction but no weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) dulaglutide in youth with type 2 diabetes. Tamborlane and colleagues have now reported the results of a randomized trial that studied the efficacy and safety of 2 mg exenatide once weekly in youth with type 2 diabetes. Similarly to the AWARD-PEDS study, A1c was significantly reduced compared with placebo, with a difference of -0.85% at 24 weeks. Also similarly to AWARD-PEDS, there was no significant difference in body weight between the GLP-1RA and placebo groups. There are now three studies showing glycemic benefits but little weight loss with GLP-1RA treatment in youth with type 2 diabetes, and while the glycemic benefits are encouraging, it remains perplexing why these studies have not demonstrated the weight loss that has consistently been demonstrated in adult studies of GLP-1RA.

Clinicians often choose a second-generation basal insulin analog (glargine U300, degludec) over a first-generation basal analog (glargine U100, detemir) because of lower rates of hypoglycemia. Randomized clinical trials and real-world evidence (RWE) studies comparing glargine U100 vs degludec have shown somewhat inconsistent results. In the newest RWE study comparing these two second-generation analogs, RESTORE-2 NAIVE, Fadini and colleagues reported that 6 months after initiating either glargine U300 or degludec in insulin-naive type 2 diabetes, there was a similar improvement in glycemia, no weight gain, and low hypoglycemia rates in each group. RESTORE-2 is another study demonstrating similar results between the two second-generation insulin analogs and helps build our understanding that these two insulins are more similar than different.

Many sodium-glucose cotransporter-2 (SGLT2) inhibitors are approved for use at two doses, but there are few clinical data regarding the metabolic impact of uptitrating an SGLT2 inhibitor from the lower to the higher dose in clinical practice. Matsumura and colleagues published the results of a retrospective, longitudinal study at a single institution in Japan. A total of 52 participants who were treated with 10 mg empagliflozin once daily were analyzed at 26 weeks after the dose had been increased to 25 mg once daily. The researchers reported a 0.6 kg weight reduction, a 0.15% reduction in A1c, and a 22.1 mg/dL reduction in triglycerides in the participants on the higher dose of empagliflozin. Although the benefits of the higher dose were rather small, this study does aid the clinician regarding the clinical impact of increasing the dose of empagliflozin.

Outcome studies with SGLT2 inhibitors have shown reductions in major adverse cardiovascular events (MACE), heart failure hospitalization, and mortality. However, clinicians may be reluctant to initiate SGLT2 inhibitors in frail individuals as they are often excluded from randomized trials and may be more likely to have side effects from this class of medications. Wood and colleagues conducted a cohort study in Australia, comparing the effectiveness of SGLT2 inhibitors to that of dipeptidyl peptidase-4 (DPP-4) inhibitors. The study was done with individuals with type 2 diabetes who were initiated on these agents within 60 days of a hospital discharge. It was noted that SGLT2 inhibitors significantly reduced MACE, heart failure hospitalization, and mortality compared with DPP-4 inhibitors, and this benefit was present in both frail and nonfrail individuals. The study did not report on tolerability issues and is limited by the cohort design, but it does suggest a cardiovascular benefit among frail patients with type 2 diabetes who are treated with SGLT2 inhibitors, and it may be reassuring when considering an SGLT2 inhibitor in a frail person.

In my July 2022 commentary, I discussed the results of AWARD-PEDS, which demonstrated a significant A1c reduction but no weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) dulaglutide in youth with type 2 diabetes. Tamborlane and colleagues have now reported the results of a randomized trial that studied the efficacy and safety of 2 mg exenatide once weekly in youth with type 2 diabetes. Similarly to the AWARD-PEDS study, A1c was significantly reduced compared with placebo, with a difference of -0.85% at 24 weeks. Also similarly to AWARD-PEDS, there was no significant difference in body weight between the GLP-1RA and placebo groups. There are now three studies showing glycemic benefits but little weight loss with GLP-1RA treatment in youth with type 2 diabetes, and while the glycemic benefits are encouraging, it remains perplexing why these studies have not demonstrated the weight loss that has consistently been demonstrated in adult studies of GLP-1RA.

Clinicians often choose a second-generation basal insulin analog (glargine U300, degludec) over a first-generation basal analog (glargine U100, detemir) because of lower rates of hypoglycemia. Randomized clinical trials and real-world evidence (RWE) studies comparing glargine U100 vs degludec have shown somewhat inconsistent results. In the newest RWE study comparing these two second-generation analogs, RESTORE-2 NAIVE, Fadini and colleagues reported that 6 months after initiating either glargine U300 or degludec in insulin-naive type 2 diabetes, there was a similar improvement in glycemia, no weight gain, and low hypoglycemia rates in each group. RESTORE-2 is another study demonstrating similar results between the two second-generation insulin analogs and helps build our understanding that these two insulins are more similar than different.

Key clinical point: Sodium-glucose cotransporter-2 inhibitors (SGLT-2I) offered advantages over dipeptidyl peptidase-4 inhibitors (DPP-4I) for preventing major adverse cardiovascular events (MACE), heart failure (HF) hospitalizations, and all-cause mortality in frail patients with type 2 diabetes (T2D) who were recently hospitalized.

Major finding: The rates of MACE (subdistribution hazard ratio [sHR] 0.51; 95% CI 0.46-0.56), HF hospitalization (sHR 0.42; 95% CI 0.36-0.49), and all-cause mortality (HR 0.38; 95% CI 0.33-0.43) were significantly lower in patients receiving SGLT-2I vs DPP-4I.

Study details: The data come from a cohort study of 32,043 patients aged ≥30 years with T2D who were recently discharged from hospital, of which 5152 received SGLT-2I and 26,891 received DPP-4I.

Disclosures: This study received no specific funding. JS Bell, JE Shaw, J Ilomaki, and M Cesari declared receiving personal fees or research grants from various sources.

Source: Wood SJ et al. Effectiveness of sodium-glucose cotransporter-2 inhibitors vs. dipeptidyl peptidase-4 inhibitors in frail people with diabetes who were recently hospitalized. Front Pharmacol. 2022;13:886834 (Jul 12). Doi: 10.3389/fphar.2022.886834

Key clinical point: Sodium-glucose cotransporter-2 inhibitors (SGLT-2I) offered advantages over dipeptidyl peptidase-4 inhibitors (DPP-4I) for preventing major adverse cardiovascular events (MACE), heart failure (HF) hospitalizations, and all-cause mortality in frail patients with type 2 diabetes (T2D) who were recently hospitalized.

Major finding: The rates of MACE (subdistribution hazard ratio [sHR] 0.51; 95% CI 0.46-0.56), HF hospitalization (sHR 0.42; 95% CI 0.36-0.49), and all-cause mortality (HR 0.38; 95% CI 0.33-0.43) were significantly lower in patients receiving SGLT-2I vs DPP-4I.

Study details: The data come from a cohort study of 32,043 patients aged ≥30 years with T2D who were recently discharged from hospital, of which 5152 received SGLT-2I and 26,891 received DPP-4I.

Disclosures: This study received no specific funding. JS Bell, JE Shaw, J Ilomaki, and M Cesari declared receiving personal fees or research grants from various sources.

Source: Wood SJ et al. Effectiveness of sodium-glucose cotransporter-2 inhibitors vs. dipeptidyl peptidase-4 inhibitors in frail people with diabetes who were recently hospitalized. Front Pharmacol. 2022;13:886834 (Jul 12). Doi: 10.3389/fphar.2022.886834

Key clinical point: Sodium-glucose cotransporter-2 inhibitors (SGLT-2I) offered advantages over dipeptidyl peptidase-4 inhibitors (DPP-4I) for preventing major adverse cardiovascular events (MACE), heart failure (HF) hospitalizations, and all-cause mortality in frail patients with type 2 diabetes (T2D) who were recently hospitalized.

Major finding: The rates of MACE (subdistribution hazard ratio [sHR] 0.51; 95% CI 0.46-0.56), HF hospitalization (sHR 0.42; 95% CI 0.36-0.49), and all-cause mortality (HR 0.38; 95% CI 0.33-0.43) were significantly lower in patients receiving SGLT-2I vs DPP-4I.

Study details: The data come from a cohort study of 32,043 patients aged ≥30 years with T2D who were recently discharged from hospital, of which 5152 received SGLT-2I and 26,891 received DPP-4I.

Disclosures: This study received no specific funding. JS Bell, JE Shaw, J Ilomaki, and M Cesari declared receiving personal fees or research grants from various sources.

Source: Wood SJ et al. Effectiveness of sodium-glucose cotransporter-2 inhibitors vs. dipeptidyl peptidase-4 inhibitors in frail people with diabetes who were recently hospitalized. Front Pharmacol. 2022;13:886834 (Jul 12). Doi: 10.3389/fphar.2022.886834

Key clinical point: Patients with upper gastrointestinal disease (UGID) receiving proton pump inhibitors (PPI) showed a dose-dependent increased risk for type 2 diabetes (T2D) compared with those not receiving PPI.

Major finding: The risk for T2D was significantly higher in patients receiving a cumulative defined daily dose (cDDD) of PPI of 31-120 mg (adjusted odds ratio [aOR] 1.20, 95% CI 1.13-1.26), 121-365 mg (aOR 1.26; 95% CI 1.19-1.33), and >365 mg (aOR 1.34; 95% CI 1.23-1.46) than in those receiving a cDDD of PPI ≤30 mg.

Study details: Findings are from a nested case-control study including 41,880 patients with UGID who received PPI, of which 20,940 who subsequently developed T2D were matched with 20,940 who did not develop T2D.

Disclosures: This study was supported by grants from Taipei Veterans General Hospital, Taiwan, and others. The authors declared no conflicts of interest.

Source: Kuo HY et al. Dose-dependent proton pump inhibitor exposure and risk of type 2 diabetes: A nationwide nested case–control study. Int J Environ Res Public Health. 2022;19(14):8739 (Jul 18). Doi: 10.3390/ijerph19148739

Key clinical point: Patients with upper gastrointestinal disease (UGID) receiving proton pump inhibitors (PPI) showed a dose-dependent increased risk for type 2 diabetes (T2D) compared with those not receiving PPI.

Major finding: The risk for T2D was significantly higher in patients receiving a cumulative defined daily dose (cDDD) of PPI of 31-120 mg (adjusted odds ratio [aOR] 1.20, 95% CI 1.13-1.26), 121-365 mg (aOR 1.26; 95% CI 1.19-1.33), and >365 mg (aOR 1.34; 95% CI 1.23-1.46) than in those receiving a cDDD of PPI ≤30 mg.

Study details: Findings are from a nested case-control study including 41,880 patients with UGID who received PPI, of which 20,940 who subsequently developed T2D were matched with 20,940 who did not develop T2D.

Disclosures: This study was supported by grants from Taipei Veterans General Hospital, Taiwan, and others. The authors declared no conflicts of interest.

Source: Kuo HY et al. Dose-dependent proton pump inhibitor exposure and risk of type 2 diabetes: A nationwide nested case–control study. Int J Environ Res Public Health. 2022;19(14):8739 (Jul 18). Doi: 10.3390/ijerph19148739

Key clinical point: Patients with upper gastrointestinal disease (UGID) receiving proton pump inhibitors (PPI) showed a dose-dependent increased risk for type 2 diabetes (T2D) compared with those not receiving PPI.

Major finding: The risk for T2D was significantly higher in patients receiving a cumulative defined daily dose (cDDD) of PPI of 31-120 mg (adjusted odds ratio [aOR] 1.20, 95% CI 1.13-1.26), 121-365 mg (aOR 1.26; 95% CI 1.19-1.33), and >365 mg (aOR 1.34; 95% CI 1.23-1.46) than in those receiving a cDDD of PPI ≤30 mg.

Study details: Findings are from a nested case-control study including 41,880 patients with UGID who received PPI, of which 20,940 who subsequently developed T2D were matched with 20,940 who did not develop T2D.

Disclosures: This study was supported by grants from Taipei Veterans General Hospital, Taiwan, and others. The authors declared no conflicts of interest.

Source: Kuo HY et al. Dose-dependent proton pump inhibitor exposure and risk of type 2 diabetes: A nationwide nested case–control study. Int J Environ Res Public Health. 2022;19(14):8739 (Jul 18). Doi: 10.3390/ijerph19148739

Key clinical point: Women with type 2 diabetes (T2D) and a history of gestational diabetes (GD) are at a higher risk for myocardial infarction (MI) and coronary artery disease compared with those with T2D and no GD history.

Major finding: Among women with T2D, those with a history of GD had a significantly higher risk for MI (adjusted odds ratio [aOR] 2.53; 95% CI 1.18-5.40) and a borderline increased risk for coronary artery disease (aOR 2.15; 95% CI 1.00-4.66) compared with those without GD history.

Study details: This cross-sectional study included 2494 women aged ≥20 years with T2D, of which 385 (15.4%) had a history of GD.

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

Source: Cui Y et al. Impact of prior gestational diabetes on long-term type 2 diabetes complications. J Diabetes Complications. 2022;36(9):108282 (Aug 2). Doi: 10.1016/j.jdiacomp.2022.108282

Key clinical point: Women with type 2 diabetes (T2D) and a history of gestational diabetes (GD) are at a higher risk for myocardial infarction (MI) and coronary artery disease compared with those with T2D and no GD history.

Major finding: Among women with T2D, those with a history of GD had a significantly higher risk for MI (adjusted odds ratio [aOR] 2.53; 95% CI 1.18-5.40) and a borderline increased risk for coronary artery disease (aOR 2.15; 95% CI 1.00-4.66) compared with those without GD history.

Study details: This cross-sectional study included 2494 women aged ≥20 years with T2D, of which 385 (15.4%) had a history of GD.

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

Source: Cui Y et al. Impact of prior gestational diabetes on long-term type 2 diabetes complications. J Diabetes Complications. 2022;36(9):108282 (Aug 2). Doi: 10.1016/j.jdiacomp.2022.108282

Key clinical point: Women with type 2 diabetes (T2D) and a history of gestational diabetes (GD) are at a higher risk for myocardial infarction (MI) and coronary artery disease compared with those with T2D and no GD history.

Major finding: Among women with T2D, those with a history of GD had a significantly higher risk for MI (adjusted odds ratio [aOR] 2.53; 95% CI 1.18-5.40) and a borderline increased risk for coronary artery disease (aOR 2.15; 95% CI 1.00-4.66) compared with those without GD history.

Study details: This cross-sectional study included 2494 women aged ≥20 years with T2D, of which 385 (15.4%) had a history of GD.

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

Source: Cui Y et al. Impact of prior gestational diabetes on long-term type 2 diabetes complications. J Diabetes Complications. 2022;36(9):108282 (Aug 2). Doi: 10.1016/j.jdiacomp.2022.108282

Key clinical point: Patients with type 2 diabetes (T2D) who initiated dulaglutide and liraglutide showed good treatment persistence and similar improvement in glycemic control along with weight loss at 12 months.

Major finding: At 12 months, a high probability of treatment persistence (0.88; 95% CI 0.86-0.90, and 0.83; 95% CI 0.80-0.85, respectively) and a significant reduction in the mean glycated hemoglobin level (−1.18% and −1.15%, respectively) were observed in patients initiating dulaglutide and liraglutide, along with body weight reduction in both the dulaglutide (−3.2 kg) and liraglutide (−3.4 kg) groups.

Study details: The data come from a prospective observational study, TROPHIES, including 2005 patients with T2D who initiated the first injectable treatment with dulaglutide (n = 1014) or liraglutide (n = 991).

Disclosures: This study was funded by Eli Lilly and Company. The authors declared receiving research support, speaker’s fees, or travel support or serving as a clinical investigator or consultant for various sources, including Eli Lilly. Six authors declared being full-time employees and shareholders of Eli Lilly.

Source: Guerci B et al. The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in type 2 diabetes patients (TROPHIES): Patient disposition, clinical characteristics, and treatment persistence at 12 months diabetes Obes Metab. 2022 (Jul 25). Doi: 10.1111/dom.14823

Key clinical point: Patients with type 2 diabetes (T2D) who initiated dulaglutide and liraglutide showed good treatment persistence and similar improvement in glycemic control along with weight loss at 12 months.

Major finding: At 12 months, a high probability of treatment persistence (0.88; 95% CI 0.86-0.90, and 0.83; 95% CI 0.80-0.85, respectively) and a significant reduction in the mean glycated hemoglobin level (−1.18% and −1.15%, respectively) were observed in patients initiating dulaglutide and liraglutide, along with body weight reduction in both the dulaglutide (−3.2 kg) and liraglutide (−3.4 kg) groups.

Study details: The data come from a prospective observational study, TROPHIES, including 2005 patients with T2D who initiated the first injectable treatment with dulaglutide (n = 1014) or liraglutide (n = 991).

Disclosures: This study was funded by Eli Lilly and Company. The authors declared receiving research support, speaker’s fees, or travel support or serving as a clinical investigator or consultant for various sources, including Eli Lilly. Six authors declared being full-time employees and shareholders of Eli Lilly.

Source: Guerci B et al. The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in type 2 diabetes patients (TROPHIES): Patient disposition, clinical characteristics, and treatment persistence at 12 months diabetes Obes Metab. 2022 (Jul 25). Doi: 10.1111/dom.14823

Key clinical point: Patients with type 2 diabetes (T2D) who initiated dulaglutide and liraglutide showed good treatment persistence and similar improvement in glycemic control along with weight loss at 12 months.

Major finding: At 12 months, a high probability of treatment persistence (0.88; 95% CI 0.86-0.90, and 0.83; 95% CI 0.80-0.85, respectively) and a significant reduction in the mean glycated hemoglobin level (−1.18% and −1.15%, respectively) were observed in patients initiating dulaglutide and liraglutide, along with body weight reduction in both the dulaglutide (−3.2 kg) and liraglutide (−3.4 kg) groups.

Study details: The data come from a prospective observational study, TROPHIES, including 2005 patients with T2D who initiated the first injectable treatment with dulaglutide (n = 1014) or liraglutide (n = 991).

Disclosures: This study was funded by Eli Lilly and Company. The authors declared receiving research support, speaker’s fees, or travel support or serving as a clinical investigator or consultant for various sources, including Eli Lilly. Six authors declared being full-time employees and shareholders of Eli Lilly.

Source: Guerci B et al. The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in type 2 diabetes patients (TROPHIES): Patient disposition, clinical characteristics, and treatment persistence at 12 months diabetes Obes Metab. 2022 (Jul 25). Doi: 10.1111/dom.14823

Key clinical point: Switching from low-dose to high-dose empagliflozin led to significant clinical benefits in patients with type 2 diabetes (T2D) and inadequate glycemic control.

Major finding: Increasing the dose of empagliflozin from 10 mg to 25 mg for 6 months significantly improved the fasting plasma glucose and glycated hemoglobin levels by −12.7 mg/dL and −13%, respectively (P < .01), along with a significant reduction in body weight (−0.6 kg), triglyceride level (−22.1 mg/dL), and c-glutamyl transpeptidase level (−6.6 U/L; P < .01) and increase in hematocrit by 0.9% after 3 months.

Study details: This was a retrospective study including 52 patients with T2D and inadequate glycemic control whose dose of empagliflozin was increased from 10 mg to 25 mg once daily.

Disclosures: This study was sponsored by Shimazu Corporation, Kyoto, Japan. The authors declared no conflicts of interest.

Source: Matsumura T et al. Clinical benefit of switching from low-dose to high-dose empagliflozin in patients with type 2 diabetes. Diabetes Ther. 2022 (Jul 15). Doi: 10.1007/s13300-022-01296-y

Key clinical point: Switching from low-dose to high-dose empagliflozin led to significant clinical benefits in patients with type 2 diabetes (T2D) and inadequate glycemic control.

Major finding: Increasing the dose of empagliflozin from 10 mg to 25 mg for 6 months significantly improved the fasting plasma glucose and glycated hemoglobin levels by −12.7 mg/dL and −13%, respectively (P < .01), along with a significant reduction in body weight (−0.6 kg), triglyceride level (−22.1 mg/dL), and c-glutamyl transpeptidase level (−6.6 U/L; P < .01) and increase in hematocrit by 0.9% after 3 months.

Study details: This was a retrospective study including 52 patients with T2D and inadequate glycemic control whose dose of empagliflozin was increased from 10 mg to 25 mg once daily.

Disclosures: This study was sponsored by Shimazu Corporation, Kyoto, Japan. The authors declared no conflicts of interest.

Source: Matsumura T et al. Clinical benefit of switching from low-dose to high-dose empagliflozin in patients with type 2 diabetes. Diabetes Ther. 2022 (Jul 15). Doi: 10.1007/s13300-022-01296-y

Key clinical point: Switching from low-dose to high-dose empagliflozin led to significant clinical benefits in patients with type 2 diabetes (T2D) and inadequate glycemic control.

Major finding: Increasing the dose of empagliflozin from 10 mg to 25 mg for 6 months significantly improved the fasting plasma glucose and glycated hemoglobin levels by −12.7 mg/dL and −13%, respectively (P < .01), along with a significant reduction in body weight (−0.6 kg), triglyceride level (−22.1 mg/dL), and c-glutamyl transpeptidase level (−6.6 U/L; P < .01) and increase in hematocrit by 0.9% after 3 months.

Study details: This was a retrospective study including 52 patients with T2D and inadequate glycemic control whose dose of empagliflozin was increased from 10 mg to 25 mg once daily.

Disclosures: This study was sponsored by Shimazu Corporation, Kyoto, Japan. The authors declared no conflicts of interest.

Source: Matsumura T et al. Clinical benefit of switching from low-dose to high-dose empagliflozin in patients with type 2 diabetes. Diabetes Ther. 2022 (Jul 15). Doi: 10.1007/s13300-022-01296-y

Key clinical point: Dapagliflozin consistently reduced the risk for cardiovascular (CV) death or hospitalization for heart failure (HHF) and kidney disease progression irrespective of the background CV medication in patients with type 2 diabetes (T2D) with a consistent safety profile.

Major finding: Dapagliflozin vs placebo led to a consistent reduction in the composite of CV death/HHF, HHF alone, and kidney-specific outcomes irrespective of the background CV medications (P_interaction > .05), with patients not using diuretics showing better kidney specific outcomes (P_interaction  =  .003). Serious adverse events were not significantly different between the dapagliflozin and placebo groups.

Study details: Findings are from a prespecified secondary analysis of the DECLARE-TIMI 58 trial including 17,160 patients with T2D and either atherosclerotic disease or multiple CV risk factors.

Disclosures: The DECLAR-TIMI 58 trial was supported by AstraZeneca. One author reported being an employee and shareholder of AstraZeneca. Some authors reported receiving research funding or support, honoraria, personal fees, or consulting or speaker fees, or serving as advisory board members for various sources, including AstraZeneca.

Source: Oyama K et al. Efficacy and safety of dapagliflozin according to background use of cardiovascular medications in patients with type 2 diabetes: A prespecified secondary analysis of a randomized clinical trial. JAMA Cardiol. 2022 (Jul 20). Doi: 10.1001/jamacardio.2022.2006

Key clinical point: Dapagliflozin consistently reduced the risk for cardiovascular (CV) death or hospitalization for heart failure (HHF) and kidney disease progression irrespective of the background CV medication in patients with type 2 diabetes (T2D) with a consistent safety profile.

Major finding: Dapagliflozin vs placebo led to a consistent reduction in the composite of CV death/HHF, HHF alone, and kidney-specific outcomes irrespective of the background CV medications (P_interaction > .05), with patients not using diuretics showing better kidney specific outcomes (P_interaction  =  .003). Serious adverse events were not significantly different between the dapagliflozin and placebo groups.

Study details: Findings are from a prespecified secondary analysis of the DECLARE-TIMI 58 trial including 17,160 patients with T2D and either atherosclerotic disease or multiple CV risk factors.

Disclosures: The DECLAR-TIMI 58 trial was supported by AstraZeneca. One author reported being an employee and shareholder of AstraZeneca. Some authors reported receiving research funding or support, honoraria, personal fees, or consulting or speaker fees, or serving as advisory board members for various sources, including AstraZeneca.

Source: Oyama K et al. Efficacy and safety of dapagliflozin according to background use of cardiovascular medications in patients with type 2 diabetes: A prespecified secondary analysis of a randomized clinical trial. JAMA Cardiol. 2022 (Jul 20). Doi: 10.1001/jamacardio.2022.2006

Key clinical point: Dapagliflozin consistently reduced the risk for cardiovascular (CV) death or hospitalization for heart failure (HHF) and kidney disease progression irrespective of the background CV medication in patients with type 2 diabetes (T2D) with a consistent safety profile.

Major finding: Dapagliflozin vs placebo led to a consistent reduction in the composite of CV death/HHF, HHF alone, and kidney-specific outcomes irrespective of the background CV medications (P_interaction > .05), with patients not using diuretics showing better kidney specific outcomes (P_interaction  =  .003). Serious adverse events were not significantly different between the dapagliflozin and placebo groups.

Study details: Findings are from a prespecified secondary analysis of the DECLARE-TIMI 58 trial including 17,160 patients with T2D and either atherosclerotic disease or multiple CV risk factors.

Disclosures: The DECLAR-TIMI 58 trial was supported by AstraZeneca. One author reported being an employee and shareholder of AstraZeneca. Some authors reported receiving research funding or support, honoraria, personal fees, or consulting or speaker fees, or serving as advisory board members for various sources, including AstraZeneca.

Source: Oyama K et al. Efficacy and safety of dapagliflozin according to background use of cardiovascular medications in patients with type 2 diabetes: A prespecified secondary analysis of a randomized clinical trial. JAMA Cardiol. 2022 (Jul 20). Doi: 10.1001/jamacardio.2022.2006

Key clinical point: Initiation of 300 units/mL insulin glargine (Gla-300) or 100 units/mL degludec (Deg-100) was associated with similar improvements in glycemic control, no weight gain, and low rates of hypoglycemia in insulin-naive patients with type 2 diabetes (T2D).

Major finding: After 6 months, both Gla-300 and Deg-100 led to a significant and similar reduction in glycated hemoglobin (between group difference [Δ] −0.01%; P  =  .49) and fasting blood glucose (Δ −2.09 mg/dL; P  =  .74) levels, with no significant changes in body weight in both treatment groups. Overall, the incidence of hypoglycemia was low, with no severe episodes reported.

Study details: This was a retrospective study including insulin-naive patients with T2D who initiated Gla-300 and were propensity matched with those who initiated Deg-100 (n = 357).

Disclosures: This study was funded by Sanofi S.r.l., Milan, Italy. Some authors declared receiving lecture fees, consulting fees, research funding, or speaking honoraria from various sources, including Sanofi. M Larosa declared being an employee and holding stock in Sanofi.

Source: Fadini GP et al. Comparative effectiveness and safety of glargine 300 U/mL versus degludec 100 U/mL in insulin-naïve patients with type 2 diabetes. A multicenter retrospective real-world study (RESTORE-2 NAIVE STUDY). Acta Diabetol. 2022 (Jul 21). Doi: 10.1007/s00592-022-01925-9

Key clinical point: Initiation of 300 units/mL insulin glargine (Gla-300) or 100 units/mL degludec (Deg-100) was associated with similar improvements in glycemic control, no weight gain, and low rates of hypoglycemia in insulin-naive patients with type 2 diabetes (T2D).

Major finding: After 6 months, both Gla-300 and Deg-100 led to a significant and similar reduction in glycated hemoglobin (between group difference [Δ] −0.01%; P  =  .49) and fasting blood glucose (Δ −2.09 mg/dL; P  =  .74) levels, with no significant changes in body weight in both treatment groups. Overall, the incidence of hypoglycemia was low, with no severe episodes reported.

Study details: This was a retrospective study including insulin-naive patients with T2D who initiated Gla-300 and were propensity matched with those who initiated Deg-100 (n = 357).

Disclosures: This study was funded by Sanofi S.r.l., Milan, Italy. Some authors declared receiving lecture fees, consulting fees, research funding, or speaking honoraria from various sources, including Sanofi. M Larosa declared being an employee and holding stock in Sanofi.

Source: Fadini GP et al. Comparative effectiveness and safety of glargine 300 U/mL versus degludec 100 U/mL in insulin-naïve patients with type 2 diabetes. A multicenter retrospective real-world study (RESTORE-2 NAIVE STUDY). Acta Diabetol. 2022 (Jul 21). Doi: 10.1007/s00592-022-01925-9

Key clinical point: Initiation of 300 units/mL insulin glargine (Gla-300) or 100 units/mL degludec (Deg-100) was associated with similar improvements in glycemic control, no weight gain, and low rates of hypoglycemia in insulin-naive patients with type 2 diabetes (T2D).

Major finding: After 6 months, both Gla-300 and Deg-100 led to a significant and similar reduction in glycated hemoglobin (between group difference [Δ] −0.01%; P  =  .49) and fasting blood glucose (Δ −2.09 mg/dL; P  =  .74) levels, with no significant changes in body weight in both treatment groups. Overall, the incidence of hypoglycemia was low, with no severe episodes reported.

Study details: This was a retrospective study including insulin-naive patients with T2D who initiated Gla-300 and were propensity matched with those who initiated Deg-100 (n = 357).

Disclosures: This study was funded by Sanofi S.r.l., Milan, Italy. Some authors declared receiving lecture fees, consulting fees, research funding, or speaking honoraria from various sources, including Sanofi. M Larosa declared being an employee and holding stock in Sanofi.

Source: Fadini GP et al. Comparative effectiveness and safety of glargine 300 U/mL versus degludec 100 U/mL in insulin-naïve patients with type 2 diabetes. A multicenter retrospective real-world study (RESTORE-2 NAIVE STUDY). Acta Diabetol. 2022 (Jul 21). Doi: 10.1007/s00592-022-01925-9

Key clinical point: Dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) did not increase the risk for fracture in patients with type 2 diabetes (T2D) compared with other antidiabetic agents or placebo.

Major finding: DPP-4i was not associated with a higher risk for total fracture compared with insulin (odds ratio [OR] 0.86; 95% CI 0.39-1.90), metformin (OR 1.41; 95% CI 0.48-4.19), sulfonylureas (OR 0.77; 95% CI 0.50-1.20), thiazolidinediones (OR 0.82; 95% CI 0.27-2.44), α-glucosidase inhibitor (OR 4.92; 95% CI 0.23-103.83), and placebo (OR 1.04; 95% CI 0.84-1.29), with findings being similar for GLP-1 RA and SGLT-2i.

Study details: The data come from a systematic review and network meta-analysis of 177 randomized controlled trials including 165,081 patients with T2D.

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

Source: Chai S et al. Risk of fracture with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes mellitus: A systematic review and network meta-analysis combining 177 randomized controlled trials with a median follow-up of 26 weeks. Front Pharmacol. 2022;13:825417 (Jul 1). Doi:  10.3389/fphar.2022.825417

Key clinical point: Dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) did not increase the risk for fracture in patients with type 2 diabetes (T2D) compared with other antidiabetic agents or placebo.

Major finding: DPP-4i was not associated with a higher risk for total fracture compared with insulin (odds ratio [OR] 0.86; 95% CI 0.39-1.90), metformin (OR 1.41; 95% CI 0.48-4.19), sulfonylureas (OR 0.77; 95% CI 0.50-1.20), thiazolidinediones (OR 0.82; 95% CI 0.27-2.44), α-glucosidase inhibitor (OR 4.92; 95% CI 0.23-103.83), and placebo (OR 1.04; 95% CI 0.84-1.29), with findings being similar for GLP-1 RA and SGLT-2i.

Study details: The data come from a systematic review and network meta-analysis of 177 randomized controlled trials including 165,081 patients with T2D.

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

Source: Chai S et al. Risk of fracture with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes mellitus: A systematic review and network meta-analysis combining 177 randomized controlled trials with a median follow-up of 26 weeks. Front Pharmacol. 2022;13:825417 (Jul 1). Doi:  10.3389/fphar.2022.825417

Key clinical point: Dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) did not increase the risk for fracture in patients with type 2 diabetes (T2D) compared with other antidiabetic agents or placebo.

Major finding: DPP-4i was not associated with a higher risk for total fracture compared with insulin (odds ratio [OR] 0.86; 95% CI 0.39-1.90), metformin (OR 1.41; 95% CI 0.48-4.19), sulfonylureas (OR 0.77; 95% CI 0.50-1.20), thiazolidinediones (OR 0.82; 95% CI 0.27-2.44), α-glucosidase inhibitor (OR 4.92; 95% CI 0.23-103.83), and placebo (OR 1.04; 95% CI 0.84-1.29), with findings being similar for GLP-1 RA and SGLT-2i.

Study details: The data come from a systematic review and network meta-analysis of 177 randomized controlled trials including 165,081 patients with T2D.

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

Source: Chai S et al. Risk of fracture with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes mellitus: A systematic review and network meta-analysis combining 177 randomized controlled trials with a median follow-up of 26 weeks. Front Pharmacol. 2022;13:825417 (Jul 1). Doi:  10.3389/fphar.2022.825417

Key clinical point: Dipeptidyl peptidase 4 inhibitors (DPP-4i), but not glucagon-like peptide 1 receptor agonists (GLP-1 RA), significantly increased the risk for acute liver injury in patients with type 2 diabetes (T2D) compared with sodium-glucose cotransporter-2 inhibitors (SGLT-2i).

Major finding: Compared with SGLT-2i, DPP-4i (hazard ratio [HR] 1.53; 95% CI 1.02-2.30), but not GLP-1 RA (HR 1.11; 95% CI 0.57-2.16), were associated with a higher risk for acute liver injury; however, the risk was significantly higher in women receiving DPP-4i (HR 3.22; 95% CI 1.67-6.21) and GLP-1 RA (HR 3.23; 95% CI 1.44-7.25).

Study details: Findings are from a population-based study including 2 new-user, active-comparator cohorts; the first cohort included 106,310 and 27,277 new users of DPP-4i and SGLT-2i, respectively, and the second cohort included 9470 and 26,936 new users of GLP-1 RA and SGLT-2i, respectively.

Disclosures: This study was funded by a Canadian Institutes of Health Research Foundation Scheme grant. L Azoulay declared receiving consulting fees from Janssen Pharmaceuticals and Pfizer outside this work.

Source: Pradhan R et al. Incretin-based drugs and the risk of acute liver injury among patients with type 2 diabetes. Diabetes Care. 2022 (Jul 22). Doi: 10.2337/dc22-0712

Key clinical point: Dipeptidyl peptidase 4 inhibitors (DPP-4i), but not glucagon-like peptide 1 receptor agonists (GLP-1 RA), significantly increased the risk for acute liver injury in patients with type 2 diabetes (T2D) compared with sodium-glucose cotransporter-2 inhibitors (SGLT-2i).

Major finding: Compared with SGLT-2i, DPP-4i (hazard ratio [HR] 1.53; 95% CI 1.02-2.30), but not GLP-1 RA (HR 1.11; 95% CI 0.57-2.16), were associated with a higher risk for acute liver injury; however, the risk was significantly higher in women receiving DPP-4i (HR 3.22; 95% CI 1.67-6.21) and GLP-1 RA (HR 3.23; 95% CI 1.44-7.25).

Study details: Findings are from a population-based study including 2 new-user, active-comparator cohorts; the first cohort included 106,310 and 27,277 new users of DPP-4i and SGLT-2i, respectively, and the second cohort included 9470 and 26,936 new users of GLP-1 RA and SGLT-2i, respectively.

Disclosures: This study was funded by a Canadian Institutes of Health Research Foundation Scheme grant. L Azoulay declared receiving consulting fees from Janssen Pharmaceuticals and Pfizer outside this work.

Source: Pradhan R et al. Incretin-based drugs and the risk of acute liver injury among patients with type 2 diabetes. Diabetes Care. 2022 (Jul 22). Doi: 10.2337/dc22-0712

Key clinical point: Dipeptidyl peptidase 4 inhibitors (DPP-4i), but not glucagon-like peptide 1 receptor agonists (GLP-1 RA), significantly increased the risk for acute liver injury in patients with type 2 diabetes (T2D) compared with sodium-glucose cotransporter-2 inhibitors (SGLT-2i).

Major finding: Compared with SGLT-2i, DPP-4i (hazard ratio [HR] 1.53; 95% CI 1.02-2.30), but not GLP-1 RA (HR 1.11; 95% CI 0.57-2.16), were associated with a higher risk for acute liver injury; however, the risk was significantly higher in women receiving DPP-4i (HR 3.22; 95% CI 1.67-6.21) and GLP-1 RA (HR 3.23; 95% CI 1.44-7.25).

Study details: Findings are from a population-based study including 2 new-user, active-comparator cohorts; the first cohort included 106,310 and 27,277 new users of DPP-4i and SGLT-2i, respectively, and the second cohort included 9470 and 26,936 new users of GLP-1 RA and SGLT-2i, respectively.

Disclosures: This study was funded by a Canadian Institutes of Health Research Foundation Scheme grant. L Azoulay declared receiving consulting fees from Janssen Pharmaceuticals and Pfizer outside this work.

Source: Pradhan R et al. Incretin-based drugs and the risk of acute liver injury among patients with type 2 diabetes. Diabetes Care. 2022 (Jul 22). Doi: 10.2337/dc22-0712