A randomized clinical trial of the efficacy and safety of sitagliptin compared with dapagliflozin in patients with type 2 diabetes mellitus and mild renal insufficiency: The CompoSIT‐R study

Abstract

AimTo compare the efficacy and safety of the dipeptidyl peptidase‐4 inhibitor sitagliptin with the sodium‐glucose transporter‐2 inhibitor dapagliflozin in patients with type 2 diabetes and mild renal insufficiency.Materials and MethodsPatients with HbA1c ≥7.0 to ≤9.5% (≥53 to ≤80 mmol/mol) and estimated glomerular filtration rate ≥60 to <90 mL/min/1.73m2 on metformin (≥1500 mg/d) ± sulfonylurea were randomized to sitagliptin 100 mg (n = 307) or dapagliflozin 5 mg titrated to 10 mg (n = 306) once daily for 24 weeks. A longitudinal data analysis model was used to test the primary hypothesis that sitagliptin is non‐inferior to dapagliflozin in reducing HbA1c at Week 24, with superiority to be tested if non‐inferiority is met. https://ClinicalTrials.gov NCT02532855.ResultsBaseline mean HbA1c (% [mmol/mol]) was 7.7 (60.9) and 7.8 (61.2), and mean eGFR (mL/min/1.73m2) was 79.4 and 76.9 for the sitagliptin and dapagliflozin groups, respectively. After 24 weeks, the between‐group difference in least squares mean (95% CI) changes from baseline in HbA1c was −0.15% (−0.26, −0.04) (−1.67 mmol/mol [−2.86, −0.48]), P = 0.006, meeting the prespecified criteria for declaring both non‐inferiority and superiority of sitagliptin versus dapagliflozin. The HbA1c goal of <7% (<53 mmol/mol) was met by 43% (sitagliptin) and 27% (dapagliflozin) of patients. No meaningful between‐group difference was observed in a pre‐specified analysis of 2‐hour incremental postprandial glucose excursion. A review of adverse events (AEs) was notable for a lower incidence of drug‐related AEs with sitagliptin compared with dapagliflozin.ConclusionsIn patients with type 2 diabetes, mild renal insufficiency and inadequate glycaemic control on metformin ± sulfonylurea, sitagliptin treatment resulted in greater improvement in glycaemic control compared with dapagliflozin and was generally well tolerated.

Pancreatic safety of sodium‐glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: A systematic review and meta‐analysis

“…Of 314 potentially eligible articles underwent full text review, 31 eligible RCTs were included . Additional four RCTs were identified in the updated search in September 2019 . Finally, 35 RCTs were included in this meta‐analysis (Figure ).…”

“…Additional four RCTs were identified in the updated search in September 2019 . Finally, 35 RCTs were included in this meta‐analysis (Figure ). The basic characteristics of the included trials are presented in Table .…”

“…Data about the effects of SGLT2 inhibitors on risk of acute pancreatitis were available from 19 trials including 32 932 patients and 41 events (a crude event rate of 0.12%) . The crude rate of acute pancreatitis was 0.13% (26 events/19 936 patients) and 0.12% (15 events/ 12 996 patients) in the SGLT2 inhibitor group and the control group, respectively.…”

“…Twenty‐six trials reported overall pancreatitis with a total of 72 events among 36 688 patients (a crude event rate of 0.20%) . The incidence of overall pancreatitis was 0.20% (45 events/22178 patients) in the SGLT2 inhibitor group and 0.19% (27 events/14510 patients) in the control group.…”

Efficacy of dapagliflozin versus sitagliptin on cardiometabolic risk factors in Japanese patients with type 2 diabetes: a prospective, randomized study (DIVERSITY-CVR)

“…Some studies have compared SGLT2 inhibitors and DPP-4 inhibitors regarding their glucose-lowering effect [10][11][12][13][14], and recent comparative studies with retrospective observational design indicated that SGLT2 inhibitors were superior to DPP-4 inhibitors for preventing cardiovascular events [15,16]. However, there is limited evidence with prospective studies on the effect of SGLT2 inhibitors versus DPP-4 inhibitors on cardiovascular risk.…”