Long-term dulaglutide use may reduce the incidence of moderate or severe erectile dysfunction in men with type 2 diabetes, according to the results of an analysis published in Lancet Diabetes Endocrinology.
Through an exploratory analysis of data from the Researching Cardiovascular Events with a Weekly Incretin in Diabetes trial (REWIND: ClinicalTrials.gov Identifier NCT01394952), researchers sought to evaluate the incidence, prevalence, and progression of erectile dysfunction in a population of men treated with dulaglutide vs placebo. The investigators also sought to determine whether the effect of dulaglutide on erectile dysfunction was consistent in terms of other diabetes-related outcomes.
REWIND was a multinational, multicenter, double-blind, placebo-controlled, randomized trial conducted at 371 sites in 24 countries. A 3-week, single-blind, run-in period included self-administered weekly placebo injections. Participants who were 100% adherent were randomly assigned to receive dulaglutide 1.5 mg or an equal volume of placebo.
The primary erectile dysfunction outcome was the first post-randomization occurrence of moderate or severe erectile dysfunction.
The cohort for the current analysis included 3725 men (mean age, 65.5±6.4 years) with erectile dysfunction. Mean duration of diabetes was 10.6±7.1 years, mean estimated glomerular filtration rate was 79.8 mL/min/1.73 m2, and mean glycated hemoglobin (HbA1c) was 7.3%.
In total, 39.9% of participants had previous cardiovascular disease, 46.6% were being treated with a β-blocker, and 4.8% were using treatment for erectile dysfunction. At baseline, 56.5% of participants reported experiencing either moderate or severe erectile dysfunction.
Following randomization, moderate or severe erectile dysfunction was seen in 1382 of the 1872 participants (73.8%) in the dulaglutide group and 1402 of the 1853 participants (75.7%) in the placebo group (crude incidence rate, 21.3 per 100 person-years vs 22 per 100 person-years, respectively; hazard ratio [HR] 0.92; 95% CI, 0.85-0.99).
A reduced hazard was reported for severe erectile dysfunction, with 15.1 per 100 patient-years in the dulaglutide group vs 15.9 per 100 patient-years in the placebo group (HR, 0.89; 95% CI, 0.82-0.97). These outcomes were “also apparent when the outcome included death as a competing event,” according to the researchers (HR, 0.92; 95% CI, 0.85-0.99).
The incidence of secondary erectile dysfunction outcomes was not reduced, but participants in the dulaglutide group had a “lesser fall” in the erectile domain subscore from baseline compared with the placebo group (least square mean difference, 0.61).
When the analysis was restricted to participants with baseline erectile dysfunction, a reduced incidence of moderate or severe erectile dysfunction was noted in the dulaglutide group. However, this effect was attenuated when the analysis was restricted to sustained erectile dysfunction.
There was a notably lower incidence of erectile dysfunction in men in the dulaglutide group vs the placebo group in a subgroup of patients with previous cardiovascular disease (HR, 0.81; 95% CI, 0.72-0.91) compared with those without this history (HR, 0.99; 95% CI, 0.90-1.10). This interaction was still significant after accounting for assessment of the other subgroups (defined by age, previous cardiovascular disease, baseline erectile function domain scores, baseline use of treatment for erectile dysfunction, and β-blocker use).
Study limitations include the exploratory nature of the study, the restricted statistical power of the subgroups, and the lack of data on “organic, psychogenic, or mixed causes” of erectile dysfunction. Generalizability is also limited.
“These findings support the hypothesis that dulaglutide reduced the incidence of moderate or severe erectile dysfunction in the REWIND trial and provide further support for its overall beneficial effect on the vasculature,” the researchers concluded.
Disclosure: This clinical trial was supported by Eli Lilly. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Bajaj HS, Gerstein HC, Rao-Melacini P, et al. Erectile function in men with type 2 diabetes treated with dulaglutide: an exploratory analysis of the REWIND placebo-controlled randomized trial. Lancet Diabetes Endocrinol. Published online June 18, 2021. doi: 10.1016/S2213-8587(21)00115-7