Efficacy and Safety of Glimepiride, Voglibose, and Metformin <scp>ER</scp> in Type 2 Diabetes: A Randomized, Active‐Controlled Study

BACKGROUND: India ranks second in the global diabetes epidemic, with about 89 million individuals living with Type 2 diabetes mellitus (T2DM). We compared the efficacy and safety of fixed-dose combination (FDC) of glimepiride, voglibose, and extended-release metformin (GLIME+VOGLI+MET-ER) with voglibose and metformin (VOGLI+MET) and glimepiride and metformin (GLIME+MET). METHODS: A Phase IV, randomized, open-label, active-controlled study was performed in adult patients with T2DM poorly controlled with metformin. Patients received twice daily doses of GLIME+VOGLI+MET-ER (1 + 0.2 + 500 mg: Trivolib 1, 2 + 0.2 + 500 mg: Trivolib 2); or VOGLI+MET (0.2 + 500 mg, 0.3 + 500 mg) or GLIME+MET (1 + 500 mg, 2 + 500 mg). The primary endpoint was the change in HbA1c from baseline. RESULTS: Of the 458 patients screened, 399 were randomized (GLIME+VOGLI+MET-ER [n = 133], VOGLI+MET (n = 135), and GLIME+MET [n = 131]). The mean baseline HbA1c was ~8.35% (~67.77 mmol/mol). All the treatments showed a significant reduction in HbA1c at Weeks 12 and 24. Mean change in % (mmol/mol) HbA1c was significantly more with GLIME+VOGLI+MET-ER versus VOGLI+MET and GLIME+MET at Week 12 (-1.02 ± 0.60 [-11.2 ± 6.52] vs. -0.68 ± 0.64 [-7.49 ± 6.95], p < 0.001 and -0.88 ± 0.49 [-9.65 ± 5.34], p = 0.0154) and Week 24 (-1.57 ± 0.74 [-17.2 ± 8.14] vs. -1.11 ± 0.80 [-12.2 ± 8.79], p < 0.001 and -1.28 ± 0.60 [-14.0 ± 6.56], p = 0.0002). Overall, 49 adverse events (AEs) were reported in 32/399 (8.0%) patients. One patient each in GLIME+VOGLI+MET-ER and VOGLI+MET groups had level 1 hypoglycemia requiring no management. No severe or serious AEs were reported. CONCLUSIONS: In adult patients with T2DM inadequately controlled on metformin monotherapy, GLIME+VOGLI+MET-ER demonstrated superior HbA1c reduction compared with VOGLI+MET and GLIME+MET at Weeks 12 and 24. Study medications were safe and well-tolerated. TRIAL REGISTRATION: Clinical Trial Registry India-CTRI/2020/11/029080 [Registered on: 12/11/2020].