PMID- 28950419 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20221207 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 20 IP - 3 DP - 2018 Mar TI - Dapagliflozin in patients with type 2 diabetes mellitus: A pooled analysis of safety data from phase IIb/III clinical trials. PG - 620-628 LID - 10.1111/dom.13124 [doi] AB - 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 (/=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. CI - (c) 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Jabbour, Serge AU - Jabbour S AUID- ORCID: 0000-0002-4080-0470 AD - Department of Endocrinology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania. FAU - Seufert, Jochen AU - Seufert J AD - Division of Endocrinology and Diabetology, Department of Internal Medicine II, University Hospital of Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany. FAU - Scheen, Andre AU - Scheen A AUID- ORCID: 0000-0001-9743-4371 AD - Department of Medicine, University of Liege, Liege, Belgium. FAU - Bailey, Clifford J AU - Bailey CJ AD - School of Life and Health Sciences, Aston University, Birmingham, UK. FAU - Karup, Cathrina AU - Karup C AD - Department of AZ Global Regulatory Affairs, Patient Safety and QA (GRAPSQA), AstraZeneca Gothenburg, Molndal, Sweden. FAU - Langkilde, Anna M AU - Langkilde AM AD - Department of R&D, AstraZeneca Gothenburg, Molndal, Sweden. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20171026 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 1ULL0QJ8UC (dapagliflozin) SB - IM MH - Adult MH - Aged MH - Amputation, Surgical/statistics & numerical data MH - Benzhydryl Compounds/*adverse effects MH - Blood Volume/physiology MH - Clinical Trials, Phase II as Topic MH - Clinical Trials, Phase III as Topic MH - Diabetes Mellitus, Type 2/*drug therapy MH - Diabetic Ketoacidosis/chemically induced MH - Double-Blind Method MH - Female MH - Fractures, Spontaneous/chemically induced MH - Glomerular Filtration Rate/drug effects MH - Glucosides/*adverse effects MH - Humans MH - Hypoglycemia/chemically induced MH - Hypoglycemic Agents/*adverse effects MH - Male MH - Middle Aged MH - Reproductive Tract Infections/chemically induced MH - Sodium-Glucose Transporter 2 Inhibitors/*adverse effects MH - Treatment Outcome MH - Urinary Tract Infections/chemically induced PMC - PMC5836959 OTO - NOTNLM OT - SGLT2 inhibitor OT - antidiabetic drug OT - dapagliflozin OT - type 2 diabetes COIS- 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. EDAT- 2017/09/28 06:00 MHDA- 2018/12/12 06:00 PMCR- 2018/03/05 CRDT- 2017/09/27 06:00 PHST- 2017/07/26 00:00 [received] PHST- 2017/09/13 00:00 [revised] PHST- 2017/09/21 00:00 [accepted] PHST- 2017/09/28 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2017/09/27 06:00 [entrez] PHST- 2018/03/05 00:00 [pmc-release] AID - DOM13124 [pii] AID - 10.1111/dom.13124 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Mar;20(3):620-628. doi: 10.1111/dom.13124. Epub 2017 Oct 26.