News about glucagon-like peptide-1 agonists (GLP-1s)
General aspects
Here is a quick update on this fascinating class of drugs—originally developed for other purposes—that are now being used as anti-obesity medications. Their growing importance to the general population is perhaps best illustrated by the fact that JAMA recently dedicated a “Patient Page” to these medications for the first time, under the heading “Medications for Obesity.”¹ The summary statement noted: “(These) medications for obesity can help promote weight loss and improve outcomes for people with type 2 diabetes, hypertension, and abnormal lipid levels”—a statement so vague that it could almost have been written by the legal team of a nutritional supplement company in order not to raise concerns with the FDA.
Medscape Medical News recently reported on a study by investigators from McGill University in Montreal, Canada, which included a systematic review of 26 randomized controlled trials. The goal was to determine which GLP-1 receptor agonist or co-agonist—either already on the market or under investigation—produced the greatest weight loss. The answer was retatrutide, a still-investigational, once-weekly triple agonist (targeting GIP, GLP-1, and glucagon receptors) from Eli Lilly and Co. It was followed by tirzepatide (Mounjaro and other brand names, also from Eli Lilly), a dual agonist, and thirdly by semaglutide (from Novo Nordisk), a single GLP-1 receptor agonist.² The full article appeared in The Annals of Internal Medicine and found no significant differences in side effect profiles among the drugs.³
The article also emphasized that treatment must be continued to prevent significant weight regain. This point was also the focus of a recent JAMA article, which examined in detail the social, ethical, financial, and ultimately medical implications of long-term treatment with these medications.⁴
References
1. JAMA Patient page. JAMA 2025;333(1):96
2. Ault A.. Medscape Medical News. January 7, 2025. https://www.medscape.com/viewarticle/retatrutide-produces-greatest-weight-loss-2025a100009a?form=fpf
3. Moiz et al., Annals Int, Med 2025; https://doi.org/10.7326/ANNALS-24-01590. Ahead of print.
4. Khan et al., JAMA 2025;333(2)113-114
GLP-1 agonists in pregnancy
This class of drugs is currently not approved for use during pregnancy. In fact, some animal studies in mice have reported an increased risk of congenital abnormalities. Consequently, most IVF clinics that prescribe these medications to infertile patients require a one-month washout period before initiating treatment cycles following the discontinuation of GLP-1 therapy. However, preliminary studies on “accidental” exposure during pregnancy have been somewhat reassuring, including a recently published review article summarizing such cases.¹
A brief article in The BMJ reported on so-called “Ozempic babies”—alleged unintended pregnancies occurring in women taking oral contraceptives.¹ The concern is that GLP-1 treatments may slow gastric emptying, potentially reducing the effectiveness of oral contraceptives and increasing the risk of unplanned pregnancies. This hypothesis, however, has not yet been validated. Additionally, some of these women—perhaps unsurprisingly—experienced miscarriages, raising further questions about whether GLP-1 agonists might increase the risk of pregnancy loss.² To date, real-world evidence does not strongly support either of these concerns. Furthermore, there is currently no plausible physiological mechanism to explain how GLP-1 agonists would cause either reduced contraceptive efficacy or increased miscarriage risk.
In a related matter, a recent Mini Review in The Journal of Clinical Endocrinology & Metabolism (JCEM) addressed the literature on potential clinical implications of delayed gastric emptying caused by single GLP-1 agonists and the dual agonist tirzepatide.³ The review found that retained gastric contents at the time of upper GI endoscopy are relatively common but only rarely result in pulmonary aspiration during anesthesia. The authors concluded that there is currently insufficient research to draw firm conclusions on this issue.
References
1. Drummond et al. Am J Obstet Gynecol 2024.08.024. https://doi.org/10.1016/jajog2024.08.024
2. Nadaradjah S. BMJ 2025;388:q2440
3. Jalleh et al., JCEM 2025;110:1-15.
GLP-1 agonists for impulse control and addiction disorders
And finally—perhaps somewhat removed from infertility practice but certainly relevant to obesity management—GLP-1 receptor agonists may also help with impulse control and addiction disorders.¹ While this potential benefit has been suspected for some time, it is now gaining increasing attention, as highlighted in a recent BMJ news article.²
References
1. Xie et al., Nat Med 2025; https://doi.org/10.1038/s41591-024-03412-w; ahead of print
2. Mahase E. BMJ 2025;388:r123