Bajaj HS, Gerstein HC, Rao-Melacini P, Basile J, Colhoun H, Conget I, Cushman WC, Dagenais GR, Franek E, Hanefeld M, Keltai M, Lakshmanan M, Lanas F, Leiter LA, Lopez-Jaramillo P, Pirags V, Pogosova N, Probstfield J, Raubenheimer P, Ryden L, Shaw JE, Sheu WH, and Xavier D
Background: Diabetes is a major risk factor for erectile dysfunction, however, the effect of GLP-1 receptor agonists on erectile dysfunction is unknown. We aimed to assess the incidence, prevalence, and progression of erectile dysfunction in men treated with dulaglutide compared with placebo, and to determine whether dulaglutide's effect on erectile dysfunction was consistent with its effect on other diabetes-related outcomes., Methods: The Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial was a double-blind, placebo-controlled randomised trial of the effect of dulaglutide on cardiovascular outcomes. REWIND was done at 371 sites in 24 countries. Men and women aged older than 50 years with type 2 diabetes, who had either a previous cardiovascular event or cardiovascular risk factors, were randomly assigned (1:1) to receive either dulaglutide or placebo. Participating men were offered the opportunity to complete the standardised International Index of Erectile Function (IIEF) questionnaire at baseline, 2 years, 5 years, and study end. We did an exploratory analysis, in which we included participants who completed a baseline and at least 1 follow-up IIEF questionnaire. The primary outcome for these analyses was the first occurrence of moderate or severe erectile dysfunction following randomisation, assessed by the erectile function subscores on IIEF. This analysis was part of the REWIND trial, which is registered with ClinicalTrials.gov, NCT01394952., Findings: Between Aug 18, 2011, and Aug 14, 2013, 3725 (70·1%) of 5312 male participants with a mean age of 65·5 years (SD 6·4 years) were analysed, of whom 1487 (39·9%) had a history of cardiovascular disease, and 2104 (56·5%) had moderate or severe erectile dysfunction at baseline. The incidence of erectile dysfunction following randomisation was 21·3 per 100 person-years in the dulaglutide group and 22·0 per 100 person-years in the placebo group (HR 0·92, 95% CI 0·85-0·99, p=0·021). Men in the dulaglutide group also had a lesser fall in erectile function subscore compared with the placebo group, with a least square mean difference of 0·61 (95% CI 0·18-1·05, p=0·006)., Interpretation: Long-term use of dulaglutide might reduce the incidence of moderate or severe erectile dysfunction in men with type 2 diabetes., Funding: Eli Lilly and Company., Competing Interests: Declaration of interests HSB has received speaking honoraria from Eli Lilly and Novo Nordisk, and research funding paid to LMC Healthcare from Amgen, AstraZeneca, Boehringer Ingelheim, Ceapro, Eli Lilly, Gilead, Janssen, Kowa Pharmaceuticals, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sanofi, and Tricida. HCG holds the McMaster–Sanofi Population Health Institute Chair in Diabetes Research and Care and reports research grants from Eli Lilly, AstraZeneca, Merck, Novo Nordisk and Sanofi, honoraria for speaking from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sanofi, DKSH, and Zuellig, and consulting fees from Abbott, Covance, Eli Lilly, Novo Nordisk, Sanofi, Pfizer and Kowa. JB reports consulting fees from Medtronic and Eli Lilly, and grant support from Eli Lilly, ReCor, and Ablative Solutions. HC reports grants from the University of Edinburgh, AstraZeneca, Novo Nordisk, Bayer, Roche, and Eli Lilly. IC reports personal fees from Medtronic, Eli Lilly, Novo Nordisk, Sanofi Aventis, Astra Zeneca, Boehringer Ingelheim, and Merck Sharp and Dohme. WCC reports a research grant to his institution (University of Tennessee, TN, USA) for the REWIND trial. GRD has received honoraria for lectures from Bayer and Eli Lilly. EF reports personal fees from AstraZeneca, Bioton, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Polfa–Tarchomin, Sanofi, and Servier. FL reports honoraria from Eli Lilly, AstraZeneca, Boehringer Ingelheim, Sanofi, Merck Sharp and Dohme, and research grants from the Population Health Research Institute. LAL reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Servier, GlaxoSmithKline, and Lexicon. PL-J reports speaking honorarium from Menarini and Abbott. JP reports payment through the University of Washington (WA, USA) for the REWIND trial. JES reports grants from Eli Lilly and Astra Zeneca, and personal fees from Astra Zeneca, Eli Lilly, Novo Nordisk, Sanofi, Mylan Pharmaceuticals, Boehringer Ingelheim, Merck Sharp and Dohme, Abbott, and Pfizer. DX reports grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Coco Cola India, the Indian Council of Medical Research, Pfizer, the UK Medical Research Council, and Wellcome Trust, and speaker fees from Eli Lilly and Sanofi. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)