Semaglutide increases the risk of erectile dysfunction in obese patients without diabetes

In a recently published study in IJIR: Your Sexual Medicine Journal, researchers assessed the risk of erectile dysfunction (ED) in obese men without diabetes after treatment with semaglutide.

Prescribing semaglutide for weight loss in obese nondiabetic patients is associated with an increased risk of erectile dysfunction: TriNetX study.

What is semaglutide? Semaglutide is an incretin-mimicking drug that increases the release of insulin from the pancreas and is therefore used to treatment of type 2 diabetes (T2D) and obesity.

Semaglutide is now considered one of the most effective anti-obesity treatments, and some scientists describe its approval by the US Food and Drug Administration (FDA) as a "paradigm shift" in the treatment of obesity. In addition to benefits for type 2 diabetes and obesity, semaglutide has been clinically proven to reduce the risk of cardiovascular disease, myocardial infarction and stroke in obese men and women.

Despite these benefits, semaglutide use is associated with sexual dysfunction, especially in men who do not have diabetes. However, more research is needed to determine the risk of this side effect in patients prescribed semaglutide.

With semaglutide becoming a popular weight loss drug, it is important to take a closer look at its known side effects.

In the present study, researchers assessed the risks of sexual dysfunction associated with the use of semaglutide in obese men without diabetes. Study participants were recruited from the TriNetX, LLC Research Network, which includes electronic health records, demographic and insurance claims data for 118 million individuals from 81 healthcare organizations.

Inclusion criteria for the study: adult men aged 18 to 50 years with medically confirmed obesity, defined as a body mass index (BMI) greater than 30, and without a diagnosis of diabetes. Individuals with a clinical history of ED, penile surgery, or testosterone deficiency were excluded.

Data was collected between June 2021 and December 2023 and included participants' medical and demographic records. Participants were divided into groups: semaglutide users and a control group, with outcomes measured including a diagnosis of ED one month or more after using semaglutide or a new diagnosis of testosterone deficiency after taking the drug.

This study was almost entirely statistical, and all statistical analyzes were performed using the TriNetX platform. Univariate analysis included chi-square and T-tests testing for differences between groups using propensity scoring.

Adjustments were made for known risk factors for ED and testosterone deficiency, such as tobacco use, alcohol use, sleep apnea, hyperlipidemia, or hypertension. A smaller group of participants was matched to their closest demographic counterparts prior to analysis to improve comparisons between groups.

Participant screening identified 3,094 individuals meeting inclusion criteria, who were then matched to an equal number of controls. Participant demographics showed a mean age of 37.8 years in both groups, 74% of whom were white. The main medical difference between the groups was BMI: the mean BMI in the case group was 38.7 kg/m2, while in the control group it was 37.2 kg/m2.

Among participants prescribed semaglutide, 1.47% were diagnosed with ED or prescribed a phosphodiesterase 5 inhibitor (PDE5I), a class of drugs widely used to treat ED. By comparison, 0.32% of patients in the control group were diagnosed with ED or prescribed PDE5I. In addition, 1.53% of cases were diagnosed with testosterone deficiency after being prescribed semaglutide, compared to 0.80% of men in the control group.

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

Semaglutide can 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 cavernous tissue, treatment with semaglutide may reduce pulsatile testosterone secretion and increase smooth muscle relaxation.

Since there is little research on the sexual side effects of semaglutide, all current explanations are speculative and require further investigation in basic research studies and clinical trials.