Increased risk of erectile dysfunction with semaglutide in non-diabetic obese patients

By Hugo Francisco de SouzaReviewed by Benedette Cuffari, M.Sc.May 26 2024

In a recent study published in the IJIR: Your Sexual Medicine Journal, researchers assess the risk of erectile dysfunction (ED) in obese and non-diabetic men following semaglutide treatment.

Study: Prescribing semaglutide for weight loss in non-diabetic, obese patients is associated with an increased risk of erectile dysfunction: a TriNetX database study. Image Credit: Korawat photo shoot / Shutterstock.com

What is semaglutide?

Semaglutide is an incretin mimetic medication that increases the release of insulin from the pancreas and, as a result, is used to treat type 2 diabetes (T2D) and obesity.

Currently, semaglutide is considered one of the most effective anti-obesity interventions, with some scientists describing the United States Food and Drug Administration (FDA) approval of this drug as a "paradigm shift" in anti-obesity treatment. In addition to its T2D and obesity benefits, semaglutide has been clinically validated to reduce the risk of cardiovascular disease, myocardial infarction, and strokes in obese men and women.

Despite these benefits, semaglutide use has been associated with sexual dysfunction, particularly in non-diabetic men. Nevertheless, additional research is needed to determine the risk of this side effect in patients prescribed semaglutide.

As semaglutide gains traction for its role in weight loss, a nuanced exploration of its known side effects becomes imperative."

About the study

In the present study, researchers assess sexual dysfunction risks associated with semaglutide use by non-diabetic and obese men. Study participants were recruited from the TriNetX, LLC Research Network, which includes electronic medical records, demographic details, and insurance claims for 118 million individuals across 81 healthcare organizations.

Inclusion criteria for participation in the study included adult men between 18 and 50 years of age with medically confirmed obesity, defined as a body mass index (BMI) value exceeding 30, and no diagnosis of diabetes. Individuals were excluded if they reported a clinical history of ED, penile surgeries, or testosterone deficiency.

Data were obtained between June 2021 and December 2023, including participants' medical and demographic records. Participants were stratified into cases, which included semaglutide users and controls with measured outcomes, including an ED diagnosis one month or more following semaglutide use or a novel testosterone deficiency diagnosis following drug administration.

The present study was almost exclusively statistical, with all statistical analyses carried out using the TriNetX platform. The univariate analysis involved the Chi-square test and T-test with between-group variation tested using propensity matching.

Corrections were made for known ED and testosterone deficiency risk factors such as tobacco use, alcohol consumption, sleep apnea, hyperlipidemia, or hypertension. The smaller cohort participants were matched to their nearest demographic neighbor before analysis to improve comparisons between cases and controls.

Study findings

Participant screening identified 3,094 individuals meeting inclusion criteria, who were then matched to an equal number of controls. Participant demographic data revealed a mean age of 37.8 across both cohorts, 74% of whom were White. The primary medical distinction between the cohorts was identified as BMI, with cases exhibiting a mean BMI of 38.7 kg/m², while controls showed a mean BMI of 37.2.

Of the study participants who were prescribed semaglutide, 1.47% were diagnosed with ED or prescribed a phosphodiesterase 5 inhibitor (PDE5I), which is a class of drugs widely used in the management of ED. Comparatively, 0.32% of control patients were diagnosed with ED or prescribed PDE5Is. Moreover, 1.53% of cases were diagnosed with testosterone deficiency after being prescribed semaglutide as compared to 0.80% of men in the matched control group.

Conclusions

The current study highlights a significant increase in the risks of both ED and testosterone deficiency in men prescribed semaglutide. Nevertheless, this increase was only 1.47%, which may be acceptable to most patients, given the weight loss and cardiovascular benefits associated with semaglutide treatment.

Semaglutide may interact with Leydig cells, which express the glucagon-like peptide-1 (GLP-1) receptor and regulate GLP-1 secretion. By stimulating GLP-1 receptors present in the cavernosal tissue, semaglutide treatment may reduce pulsatile testosterone secretion and increase smooth muscle relaxation.

As there is scant research investigating the sexual side effects of semaglutide, all current explanations are purely speculation that necessitate further exploration in basic science research and clinical trials."