Dapagliflozin in patients with type 2 diabetes mellitus: A pooled analysis of safety data from phase IIb/III clinical trials

Diabetes Obes Metab. 2018 Mar;20(3):620-628. doi: 10.1111/dom.13124. Epub 2017 Oct 26.

Abstract

Aim: To evaluate the safety and tolerability of dapagliflozin, a highly selective sodium-glucose co-transporter-2 inhibitor, in patients with type 2 diabetes mellitus (T2DM).

Methods: Data were pooled from 13 placebo-controlled trials of up to 24 weeks' duration (dapagliflozin, n = 2360; placebo, n = 2295). Larger placebo-/comparator-controlled pools of 21 (≤208 weeks; dapagliflozin, n = 5936; control, n = 3403) and 30 trials (≥12 weeks; dapagliflozin, n = 9195; control, n = 4629) assessed the rare adverse events (AEs) of diabetic ketoacidosis (DKA) and lower limb amputation, respectively.

Results: Over 24 weeks, the overall incidence of AEs and serious AEs (SAEs) was similar for dapagliflozin and placebo: 60.0% vs 55.7% and 5.1% vs 5.4%, respectively. Rates of hypoglycaemia, volume depletion AEs, urinary tract infections (UTIs) and fractures were balanced between the groups. Genital infections were more frequent with dapagliflozin (5.5%) vs placebo (0.6%) and renal function AEs occurred in 3.2% vs 1.8% of patients (the most common renal AE was decreased creatinine clearance: 1.1% vs 0.7%). In the 21-study pool, 1 SAE of DKA and 3 AEs of ketonuria/metabolic acidosis occurred with dapagliflozin vs none with control; estimated combined incidence for these events was 0.03% (95% confidence interval 0.010-0.089). In the 30-study pool, lower limb amputation occurred in 8 (0.1%) and 7 (0.2%) patients receiving dapagliflozin and control, respectively.

Conclusion: The overall incidence rates of AEs and SAEs were similar in the dapagliflozin and placebo/control groups, including the incidence of hypoglycaemia, volume depletion, fractures, UTIs, amputations and DKA. Genital infections were more frequent with dapagliflozin than placebo.

Keywords: SGLT2 inhibitor; antidiabetic drug; dapagliflozin; type 2 diabetes.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Aged
  • Amputation / statistics & numerical data
  • Benzhydryl Compounds / adverse effects*
  • Blood Volume / physiology
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Ketoacidosis / chemically induced
  • Double-Blind Method
  • Female
  • Fractures, Spontaneous / chemically induced
  • Glomerular Filtration Rate / drug effects
  • Glucosides / adverse effects*
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / adverse effects*
  • Male
  • Middle Aged
  • Reproductive Tract Infections / chemically induced
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects*
  • Treatment Outcome
  • Urinary Tract Infections / chemically induced

Substances

  • Benzhydryl Compounds
  • Glucosides
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • dapagliflozin