Men should use it with caution! This weight loss drug can significantly increase the risk of ED

No dieting, no exercise, just a small pill, you can achieve effective weight loss, who doesn't love this way of weight loss? It's no wonder that semaglutide, which is famous for its weight loss effect, once became a "net celebrity weight loss drug" that attracted thousands of obese people.

Semaglutide was originally used to treat type 2 diabetes. In June 2021, the U.S. FDA approved Semaglutide as a weight loss drug, which has shown high efficacy in weight loss. The core ingredient of Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist, which can achieve weight loss by reducing hunger and calorie intake.

Semaglutide was also found to reduce the risk of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke in obese men and women without diabetes. In March 2024, the U.S. FDA approved a new indication for semaglutide - to reduce the risk of cardiovascular death, heart attack, and stroke in adults with cardiovascular disease and obesity or overweight.

There is no doubt that semaglutide is a drug with diverse functions and excellent efficacy, but it has also been shown to have multiple side effects.

Semaglutide can cause gastrointestinal discomfort such as nausea, vomiting, constipation, and diarrhea. In 2018, Patrick M O'Neil and others from the Medical University of South Carolina published a research paper titled Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial in The Lancet. The study showed that about 5% of people who lost weight could not tolerate semaglutide due to persistent gastrointestinal problems and had to stop taking the drug.

There are reports that users of semaglutide experience a reduction in healthy-looking fat on their faces, leading to sagging and aging of the face. In 2021, Satoshi Ida et al. from the Japanese Red Cross Ise Hospital published a research paper titled Effects of Antidiabetic Drugs on Muscle Mass in Type 2 Diabetes Mellitus in the journal Current Diabetes Reports. The study conducted a meta-analysis of 18 randomized controlled trials of GLP-1 receptor agonists. The results showed that semaglutide significantly reduced "fat-free mass," and the researchers concluded: "It is important to pay attention to muscle loss."

In addition to being shown to cause gastrointestinal side effects, muscle loss and other effects, semaglutide has also been shown to increase the risk of erectile dysfunction.

In May 2024, Corey Able et al. from the University of Texas Medical Branch published a research paper titled Prescribing semaglutide for weight loss in non-diabetic, obese patients is associated with an increased risk of erectile dysfunction: a TriNetX database study in the International Journal of Impotence Research, a subsidiary of Nature. The study explored the effects of semaglutide on sexual function in non-diabetic, obese male patients.

A total of 3094 nondiabetic, obese (BMI > 30) men aged 18 to 50 years who were prescribed semaglutide were enrolled and subsequently matched with an equal number of controls consisting of nondiabetic, obese men who had never been prescribed semaglutide.

The primary outcome of the study was the risk of a new diagnosis of erectile dysfunction and/or use of phosphodiesterase-5 inhibitors (PDE5i), a medication used to treat erectile dysfunction, within at least one month after the initial prescription of semaglutide. The secondary outcome was the risk of a new diagnosis of testosterone deficiency after semaglutide prescription.

Results showed that 1.47% of nondiabetic, obese men who were prescribed semaglutide were diagnosed with erectile dysfunction (ED) or used a PDE5 inhibitor, compared with 0.32% in the matched control group. After taking semaglutide, 1.53% of nondiabetic, obese men were diagnosed with testosterone deficiency, compared with 0.80% in the matched control group. There was no significant difference between the two groups in the diagnosis rate of benign prostatic hyperplasia after taking semaglutide.

Comparison of the risk of ED, testosterone deficiency, and benign prostatic hyperplasia in men taking semaglutide and a control group not taking semaglutide

Therefore, the researchers concluded that among men aged 18 to 50 years, patients prescribed semaglutide had a significantly increased risk of erectile dysfunction (ED) and testosterone deficiency compared with the control group. However, the rate of ED was low, only 1.47%, and considering its potential weight loss and cardiac benefits, this risk is acceptable for most obese men who want to achieve efficient weight loss.

The researchers speculated on the mechanism by which semaglutide causes an increased risk of erectile dysfunction and testosterone deficiency. Semaglutide may interact with Leydig cells that express GLP-1 receptors and regulate GLP-1 secretion. Semaglutide may reduce the pulsatile secretion of testosterone and increase the relaxation of smooth muscles by stimulating GLP-1 receptors present in the corpus cavernosum tissue, thereby increasing the risk of erectile dysfunction and testosterone deficiency.

However, since there are almost no studies exploring the side effects of semaglutide on sexual health, all current explanations are purely speculative, and the mechanism by which semaglutide causes an increased risk of erectile dysfunction and testosterone deficiency needs to be further explored in basic science research and clinical trials.

Given these findings, clinicians can better inform patients of the risk of sexual dysfunction listed in the drug label and monitor sexual function prophylactically after prescribing semaglutide to maximize treatment benefits and address potential barriers that may lead to discontinuation.

References:

[1] O'Neil PM, Birkenfeld AL, McGowan B, Mosenzon O, Pedersen SD, Wharton S, Carson CG, Jepsen CH, Kabisch M, Wilding JPH. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomized, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018 Aug 25;392(10148):637-649. doi: 10.1016/S0140-6736(18)31773-2IF: 168.9 Q1 . Epub 2018 Aug 16. PMID: 30122305.

[2] Ida S, Kaneko R, Imataka K, Okubo K, Shirakura Y, Azuma K, Fujiwara R, Murata K. Effects of Antidiabetic Drugs on Muscle Mass in Type 2 Diabetes Mellitus. Curr Diabetes Rev. 2021;17(3):293-303. doi: 10.2174/1573399816666200705210006. PMID: 32628589.

[3] Able C, Liao B, Saffati G, Maremanda A, Applewhite J, Nasrallah AA, Sonstein J, Alzweri L, Kohn TP. Prescribing semaglutide for weight loss in non-diabetic, obese patients is associated with an increased risk of erectile dysfunction: a TriNetX database study. Int J Impot Res. 2024 May 22. doi: 10.1038/s41443-024-00895-6. Epub ahead of print. PMID: 38778151.