Efficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes: a randomized double‐blind placebo‐controlled 102‐week trial

Abstract Aims To assess initial pharmacotherapy of Type 2 diabetes with the sodium‐glucose cotransporter‐2 inhibitor dapagliflozin. Methods This double‐blind, placebo‐controlled trial, randomly allocated people with Type 2 diabetes aged 18–77 years and inadequate glycaemic control on diet and exercise [HbA 1c 53–86 mmol/mol (7.0–10.0%)] to receive placebo ( n = 75) or dapagliflozin monotherapy 2.5 mg ( n = 65), 5 mg ( n = 64) or 10 mg ( n = 70) once daily in the morning. After 24 weeks, low‐dose double‐blind metformin 500 mg/day was added to the placebo group regimen (placebo+low‐dose metformin group). Changes in HbA 1c level, fasting plasma glucose and body weight, as well as adverse events, were assessed over 102 weeks. Results Of the 274 participants randomized, 167 completed the study (60.9%). At 102 weeks, significant differences vs placebo+low‐dose metformin with dapagliflozin 5 and 10 mg were observed for HbA 1c (−5.8 mmol/mol [−0.53%], P = 0.018; and −4.8 mmol/mol [−0.44%], P = 0.048), respectively); and for FPG (−0.69 mmol/L, P = 0.044; and −1.12 mmol/l, P = 0.001, respectively). For body weight, the difference between the dapagliflozin 10‐mg group and the placebo+low‐dose metformin group was significant (−2.60 kg; P = 0.016). Hypoglycaemic events were uncommon, with rates of 5.3% for placebo+low‐dose metformin group and 0–4.6% for the dapagliflozin groups. Genital infections and urinary tract infections were more common in the dapagliflozin groups than in the placebo+low‐dose metformin group. Conclusions Dapagliflozin as monotherapy in treatment‐naïve people with early Type 2 diabetes improved glycaemic control and reduced weight without increasing hypoglycaemia over 102 weeks. Dapagliflozin may provide an alternative initial pharmacotherapy in such people.