Objective To assess the efficacy and safety of fixed-dose combinations (FDC) of triple-drug dapagliflozin, sitagliptin, and metformin (DSM) compared with FDC of two-drug sitagliptin and metformin (SM), in Indian adult patients with type 2 diabetes (T2D). Methods A multicentric, randomized, double-blind, active-controlled, Phase 3 study (CTRI/2021/10/037461) was conducted on 274 Indian adult patients with T2D. Patients were randomized (1:1) to receive either an FDC of triple-drug ( n  = 137) dapagliflozin propanediol 10 mg, sitagliptin phosphate 100 mg, and metformin hydrochloride 1000 mg extended-release (DSM) or FDC of two-drug ( n  = 137) sitagliptin phosphate 100 mg and metformin hydrochloride 1000 mg sustained-release (SM), for 16 weeks. The primary endpoint was a change in HbA1c, while the secondary endpoints were changes in fasting plasma glucose (FPG), postprandial glucose (PPG), body weight, and safety. Results Both DSM and SM FDCs reduced HbA1c significantly (-1.45% and -1.00%, respectively, both p  < 0.0001), however, HbA1c lowering was superior with DSM (∆ -0.45%; p  = 0.0005) compared to SM, at week 16. Similarly, both DSM and SM FDCs reduced FPG and PPG significantly, however, FPG (∆ -12.4 mg/dl; p  = 0.003) and PPG reduction (∆ -18.45 mg/dl; p  = 0.01) were significantly superior to DSM compared to SM, respectively. No significant reduction in body weight was observed between the two arms. Both FDCs were well tolerated. Conclusion FDC of DSM was superior to SM in reducing HbA1c, FPG, and PPG in Indian adults with T2D. Both triple and dual FDCs had optimal safety profiles.