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

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

Serge Jabbour  1 , Jochen Seufert  2 , Andre Scheen  3 , Clifford J Bailey  4 , Cathrina Karup  5 , Anna M Langkilde  6
Affiliations
Review

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

Serge Jabbour et al. Diabetes Obes Metab. 2018 Mar.

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.

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Conflict of interest statement

S. J. is a consultant for AstraZeneca, Janssen and Eli Lilly. J. S. has attended advisory boards and/or speaker's bureaus for Takeda, Bayer, Novartis, Merck Sharp & Dohme, Amgen, AstraZeneca, Bristol‐Myers Squibb, Novo Nordisk, Sanofi, Berlin‐Chemie, Eli Lilly, Boehringer Ingelheim, Merck, Roche, Ipsen, Pfizer, Janssen and LifeScan, and has received project‐specific research support from AstraZeneca, Takeda, Novartis, Merck Sharp & Dohme, Amgen, GlaxoSmithKline, Novo Nordisk, Sanofi, Ipsen, Pfizer, Janssen, Servier, Eli Lilly, Apitope, Intarcia and Roche. A.S. has attended advisory boards and/or speaker's bureaus for AstraZeneca, Novo Nordisk, Eli Lilly, Sanofi, Merck Sharp & Dohme, Boehringer Ingelheim and Janssen, and has received research support from Novo Nordisk. C. J. B. received grants and personal fees from AstraZeneca, Bristol‐Myers Squibb, Sanofi and personal fees from Boehringer Ingelheim, Eli Lilly, Johnson & Johnson, Merck Sharp & Dohme, Novo Nordisk, Elcelyx and Poxel, outside of the submitted work. C. K. and A. M. L. are employees and stockholders of AstraZeneca.

Figures

Figure 1
Figure 1
Values for eGFR over time (13‐study pool). eGFR was calculated using the Modification in Diet and Renal Disease (MDRD) formula. BL, baseline; s.e., standard error. Patients at baseline denote the number of treated patients with non‐missing baseline values
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