Prescribing semaglutide for weight loss in non-diabetic, obese patients is associated with an increased risk of erectile dysfunction: a TriNetX database study

Semaglutide was approved in June 2021 for weight loss in non-diabetic, obese patients. While package inserts include sexual dysfunction as a side effect, no study has assessed the degree of this risk. The objective of our study is to assess the risk of developing erectile dysfunction after semaglutide is prescribed for weight loss in obese, non-diabetic men. The TriNetX Research database was used to identify men without a diagnosis of diabetes ages 18 to 50 with BMI > 30 who were prescribed semaglutide after June 1st, 2021. Men were excluded if they had a prior erectile dysfunction diagnosis, any phosphodiesterase-5 inhibitors prescription, intracavernosal injections, penile prosthesis placement, history of testosterone deficiency, testosterone prescription, pelvic radiation, radical prostatectomy, pulmonary hypertension, or were deceased. We further restricted our cohort to non-diabetic, obese men by excluding men with a prior diabetes mellitus diagnosis, a hemoglobin A1c > 6.5%, or having ever received insulin or metformin. Men were then stratified into cohorts of those that did and did not receive a semaglutide prescription. The primary outcome was the risk of new ED diagnosis and/or new prescription of phosphodiesterase type 5 inhibitors at least one month after prescription of semaglutide. The secondary outcome was risk of testosterone deficiency diagnosis. Risk was reported using risk ratios with 95% confidence intervals (95% CI). 3,094 non-diabetic, obese men ages 18-50 who received a prescription of semaglutide were identified and subsequently matched to an equal number cohort of non-diabetic, obese men who never received a prescription of semaglutide. After matching, average age at index prescription for non-diabetic, obese men was 37.8 +/- 7.8 and average BMI at index prescription was 38.6 +/- 5.6. Non-diabetic men prescribed semaglutide were significantly more likely to develop erectile dysfunction and/or were prescribed phosphodiesterase type 5 inhibitors (1.47% vs 0.32%; RR: 4.5; 95% CI [2.3, 9.0]) and testosterone deficiency (1.53% vs 0.80%; RR: 1.9; 95% CI [1.2, 3.1]) when compared to the control cohort of non-diabetic men who never received a semaglutide prescription.