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

Aim: To 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 methods: Patients 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. ClinicalTrials.gov NCT02532855.

Results: Baseline 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.

Conclusions: In 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.

Keywords: clinical trial; dapagliflozin; sitagliptin; type 2 diabetes.

Figure 1

Study design. eGFR, estimated glomerular filtration rate; q.d., once daily; SU, sulfonylurea; R, randomization.¹Subjects initiated dapagliflozin 5 mg q.d. at Randomization/Visit 3/Day 1 and were to uptitrated to dapagliflozin 10 mg q.d. at Visit 4/Week 4. ²The interval between Visit 1 and Visit 2 for eligible subjects was to be at least 2 weeks and no more than approximately 6 weeks. ³Subjects entering the study on metformin remained on a stable dose of metformin; subjects entering on metformin + an SU remained on stable doses of both agents

Figure 2

HbA1c measures through week 24: A, LS mean ± SE change from baseline HbA1c (%); black circles = sitagliptin, open circles = dapagliflozin; B, percentage of patients at goal of HbA1c <7% at week 24. For both A and B, results were calculated using the LDA model described in Methods