Dapagliflozin in patients with type 2 diabetes mellitus: A pooled analysis of safety data from phase IIb/III clinical trials. Issue 3 (26th October 2017)

• Record Type: Journal Article
• Authors: Jabbour, Serge; Seufert, Jochen; Scheen, Andre; Bailey, Clifford J.; Karup, Cathrina; Langkilde, Anna M.
• Is Part Of: Diabetes, obesity & metabolism. Volume 20:Issue 3(2018)
• Page Start: 620
• Page End: 628
• Publication Date: 2017-10-26
• Subjects: antidiabetic drug -- dapagliflozin -- SGLT2 inhibitor -- type 2 diabetes; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.13124
• Languages: English
• ISSNs: 1462-8902

Abstract

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.