Increased Risk of Erectile Dysfunction with Semaglutide
Semaglutide, an incretin mimetic medication, enhances insulin release from the pancreas and is widely used to treat type 2 diabetes (T2D) and obesity. Recognized as one of the most effective anti-obesity treatments, its approval by the United States Food and Drug Administration (FDA) marked a significant advancement in obesity management. Beyond its benefits for T2D and obesity, semaglutide has been shown to lower the risk of cardiovascular disease, heart attacks, and strokes in obese individuals.
However, despite these advantages, semaglutide has been associated with sexual dysfunction, particularly in non-diabetic men. More research is necessary to fully understand this potential side effect.
Semaglutide Increases Erectile Dysfunction
In this recent study, researchers investigated the risk of sexual dysfunction linked to semaglutide use in non-diabetic obese men. Participants were recruited from the TriNetX, LLC Research Network, which includes electronic medical records, demographic information, and insurance claims for 118 million individuals from 81 healthcare organizations.
Men aged 18 to 50 with medically confirmed obesity (BMI over 30) and no diabetes diagnosis were eligible. Exclusions included those with a history of erectile dysfunction (ED), penile surgeries, or testosterone deficiency.
Data from June 2021 to December 2023 were analyzed, with participants’ medical and demographic records scrutinized. Participants were divided into two groups: those using semaglutide (cases) and controls. Outcomes measured included ED diagnosis one month or more after semaglutide use or a new testosterone deficiency diagnosis post-treatment.
The study primarily utilized statistical analyses conducted via the TriNetX platform. Univariate analysis involved Chi-square tests and T-tests, with propensity matching used to address between-group variations. Adjustments were made for known ED and testosterone deficiency risk factors, including tobacco use, alcohol consumption, sleep apnea, hyperlipidemia, and hypertension.
Non Diabetic Men ED with Semaglutide
Out of 3,094 participants meeting the inclusion criteria, an equal number of controls were matched for comparison. The average age across both groups was 37.8 years, with 74% identifying as White. The main difference between cohorts was BMI, with cases showing a mean BMI of 38.7 kg/m² and controls a mean BMI of 37.2 kg/m².
Among semaglutide users, 1.47% were diagnosed with ED or prescribed phosphodiesterase 5 inhibitors (PDE5Is), compared to 0.32% of the control group. Additionally, 1.53% of cases developed testosterone deficiency after semaglutide use, versus 0.80% in the control group.
Takeaway: Semaglutide Increases Erectile Dysfunction
This study reveals a notable increase in the risk of ED and testosterone deficiency among men prescribed semaglutide. Although the increase in risk is relatively small (1.47%), it is significant given the overall benefits of semaglutide in weight loss and cardiovascular health.
The potential interaction of semaglutide with Leydig cells, which regulate GLP-1 secretion and express the GLP-1 receptor, might explain these findings. By stimulating GLP-1 receptors in the cavernosal tissue, semaglutide could reduce pulsatile testosterone secretion and enhance smooth muscle relaxation, leading to sexual dysfunction.
As the research on semaglutide’s sexual side effects is limited, further basic science studies and clinical trials are needed to understand these observations fully.