PMID- 32372290 OWN - NLM STAT- MEDLINE DCOM- 20210208 LR - 20220210 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 37 IP - 8 DP - 2020 Aug TI - Pooled Safety and Tolerability Analysis of Empagliflozin in Patients with Type 2 Diabetes Mellitus. PG - 3463-3484 LID - 10.1007/s12325-020-01329-7 [doi] AB - INTRODUCTION: The aim of this analysis was to characterize the safety and tolerability of empagliflozin in patients with type 2 diabetes mellitus (T2DM) who were randomized to empagliflozin (10/25 mg) or placebo in clinical trials. METHODS: Pooled data from 20 trials were analyzed for patients with T2DM treated with empagliflozin 10 mg (n = 4858), empagliflozin 25 mg (n = 5057), or placebo (n = 4904). The dataset comprised 15 randomized phase I-III trials, an extension trial and dose escalation studies. Adverse events (AEs) were assessed descriptively in participants who took >/= 1 dose of study drug. AE incidence rates per 100 patient-years were calculated to adjust for differences in drug exposure between trials. RESULTS: Total exposure was 16,480 and 7857 patient-years in the pooled empagliflozin 10/25 mg and placebo groups, respectively. The incidence of any AEs, AEs leading to treatment discontinuation, severe AEs, and serious AEs was similar across groups. The frequency of serious AEs requiring hospitalization was 18.6% for the empagliflozin 10/25 mg group and 21.3% for the placebo group. The empagliflozin 10/25 mg group was not associated with a higher rate of confirmed hypoglycemia versus placebo, except in patients co-administered insulin and/or a sulfonylurea (31.5% vs. 30.2%, respectively). The incidence of events consistent with urinary tract infections (UTI) was also similar for the empagliflozin 10/25 mg group versus placebo (9.27 vs. 9.70/100 patient-years, respectively). History of UTI was identified as a risk factor for UTI during treatment. Events consistent with genital infections occurred more frequently with empagliflozin 10/25 mg than placebo (3.54 vs. 0.95/100 patient-years, respectively). The frequency of AEs consistent with volume depletion was similar across groups, but higher with empagliflozin 10/25 mg than placebo in patients aged 75 to < 85 years and those on loop diuretics at baseline. CONCLUSION: This comprehensive analysis confirms that both empagliflozin 10 mg and 25 mg are well tolerated in patients with T2DM, reinforcing the established clinical safety profile of empagliflozin. FAU - Kinduryte Schorling, Ona AU - Kinduryte Schorling O AD - Boehringer Ingelheim International GmbH, Ingelheim, Germany. FAU - Clark, Douglas AU - Clark D AD - Boehringer Ingelheim International GmbH, Ingelheim, Germany. FAU - Zwiener, Isabella AU - Zwiener I AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. FAU - Kaspers, Stefan AU - Kaspers S AD - Boehringer Ingelheim International GmbH, Ingelheim, Germany. FAU - Lee, Jisoo AU - Lee J AD - Boehringer Ingelheim International GmbH, Ingelheim, Germany. FAU - Iliev, Hristo AU - Iliev H AD - Boehringer Ingelheim International GmbH, Ingelheim, Germany. hristo.iliev@boehringer-ingelheim.com. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200505 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) MH - Aged MH - Aged, 80 and over MH - Benzhydryl Compounds/*therapeutic use MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/*drug therapy MH - *Drug-Related Side Effects and Adverse Reactions MH - Female MH - Glucosides/*therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Male MH - Middle Aged MH - Placebo Effect MH - Risk Factors MH - Sodium-Glucose Transporter 2 Inhibitors/*therapeutic use PMC - PMC7370973 OAB - Empagliflozin is approved to treat adults with type 2 diabetes mellitus (T2DM) insufficiently controlled by diet and exercise. It lowers blood glucose levels by inhibiting sodium-glucose co-transporter-2 (SGLT2), a protein involved in glucose reabsorption by the kidneys. By blocking SGLT2, glucose is removed in urine instead of being reabsorbed into the bloodstream. Numerous clinical studies have shown the effectiveness and safety of empagliflozin, but recent reports of two types of serious side effects [fractures and lower limb amputations (LLAs)] associated with another drug in the class, canagliflozin, has triggered a review of the risk associated with taking SGLT2 inhibitors. To examine the safety and tolerability of empagliflozin we pooled data from 20 clinical trials involving over 15,000 patients with T2DM who received either empagliflozin or placebo (control). We found that the risk of side effects was similar whether patients received empagliflozin or placebo. This included side effects that led to treatment being stopped as well as severe and serious side effects, including fractures and LLAs. Empagliflozin was not associated with a higher rate of hypoglycemia (low blood sugar) versus placebo, except in patients also treated with insulin and/or a sulfonylurea (31.5% vs. 30.2%, respectively). The risk of urinary tract infections was also similar for empagliflozin versus placebo (9.27 vs. 9.70/100 patient-years, respectively). However, genital infections, as anticipated, occurred more frequently in patients treated with empagliflozin than placebo (3.54 vs. 0.95/100 patient-years, respectively). Overall, this analysis confirms the results of previous studies showing that empagliflozin is well tolerated in patients with T2DM. OABL- eng OTO - NOTNLM OT - Adverse drug event OT - Adverse drug reaction OT - Drug side effects OT - Hypoglycemia OT - Ketoacidosis OT - SGLT2 inhibitor EDAT- 2020/05/07 06:00 MHDA- 2021/02/09 06:00 PMCR- 2020/05/05 CRDT- 2020/05/07 06:00 PHST- 2020/01/28 00:00 [received] PHST- 2020/05/07 06:00 [pubmed] PHST- 2021/02/09 06:00 [medline] PHST- 2020/05/07 06:00 [entrez] PHST- 2020/05/05 00:00 [pmc-release] AID - 10.1007/s12325-020-01329-7 [pii] AID - 1329 [pii] AID - 10.1007/s12325-020-01329-7 [doi] PST - ppublish SO - Adv Ther. 2020 Aug;37(8):3463-3484. doi: 10.1007/s12325-020-01329-7. Epub 2020 May 5.