‘Modest’ Erectile Dysfunction Benefit With GLP-1 Agonist

GLP-1 receptor agonist treatment in men with type 2 diabetes may thwart some new cases of erectile dysfunction, an exploratory analysis of a randomized trial suggested.

The findings, from the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial, showed that slightly fewer men developed erectile dysfunction while on long-term treatment with once-weekly dulaglutide (Trulicity), reported Harpreet S. Bajaj, MD, of LMC Diabetes & Endocrinology in Ontario, Canada, and colleagues.

During a maximum follow-up of 8 years, the incidence of erectile dysfunction was 21.3 per 100 person-years for men on dulaglutide and 22.0 per 100 person-years in the placebo group (HR 0.92, 95% CI 0.85-0.99, P=0.021), the team noted in the study online in The Lancet Diabetes & Endocrinology.

After randomization, a total of 73.8% of men on dulaglutide had moderate or severe erectile dysfunction — defined as an erectile function subscore of 16 or less — compared with 75.7% of those on placebo.

Regarding severe erectile dysfunction, men on dulaglutide had an 11% reduced risk when compared with men on placebo (HR 0.89, 0.82-0.97, P=0.006).

Men on dulaglutide also saw less of a fall in erectile function domain subscore from baseline versus placebo (least square mean difference of 0.61, 95% CI 0.18-1.05, P=0.006).

The researchers pointed out that while these men on dulaglutide had a lower incidence of erectile dysfunction and didn’t have a worsening of erectile dysfunction, there also wasn’t necessarily an improvement in symptoms.

“Clinical practice guidelines suggest that evidence for prevention of diabetes-related chronic consequence should be considered when choosing glucose-lowering medications,” Bajaj and co-authors wrote. “Our findings suggest that erectile dysfunction, which is a common consequence of type 2 diabetes in men, should be included among these considerations.”

“The guidelines also suggest that erectile dysfunction and other outcomes might share common underlying vascular mechanisms that could be favorably affected by dulaglutide and should continue to be investigated in future studies,” the team added.

The REWIND trial included men and women ages 50 and older from 24 countries with established or new-onset type 2 diabetes. All participants’ HbA1c levels were less than 9.5% and had to be on stable doses of up to two oral glucose-lowering agents. All participants over 50 also had to have a history of vascular disease for inclusion, while those 55 and older had to have myocardial ischemia; coronary, carotid, or lower extremity artery stenosis exceeding 50%; left ventricular hypertrophy; an estimated glomerular filtration rate less than 60 mL/min per 1.73 m2; or albuminuria. Participants who were 60 and older had to have at least two cardiovascular risk factors for inclusion.

At baseline, 56.5% of participants had moderate or severe erectile dysfunction; only 17.5% reported no erectile dysfunction, defined as a subscore of 26 or higher.

Because the trial was restricted only to participants with underlying vascular disease, Bajaj’s group pointed out that the slight benefit seen in erectile dysfunction might be due to dulaglutide’s salutary vascular effects, which also led to improvements in cardiovascular outcomes like a risk reduction in stroke, kidney disease, and slowing of cognitive decline.

The small benefit on erectile dysfunction seen with dulaglutide is not a slam dunk, suggested the author of an accompanying commentary. Calling the benefits “modest,” Sten Madsbad, MD, DMSc, of Hvidovre Hospital in Copenhagen, Denmark, said this particular exploratory analysis doesn’t do much to uncover how dulaglutide might improve erectile dysfunction and that one key limitation was a lack of data on serum testosterone.

He did, however, agree with the researchers that the subgroup analyses showed that the benefit was restricted only to men with manifest cardiovascular disease, suggesting that there is a vascular-related mechanism of action at play.

Madsbad explained that although the benefits were minor, the findings are still “new and useable information about the benefits of dulaglutide” and that “erectile dysfunction should be considered by physicians when choosing pharmacological treatment including glucose-lowering medications for men with type 2 diabetes,” especially for those also with co-morbid cardiovascular disease.