This transcript has been edited for clarity.
In this podcast, we’re going to talk about that perennial hot topic for primary care, the GLP-1 receptor agonists. I’m going to focus on some of the recently highlighted side effects of GLP-1s, which have featured in the lay media and medical literature and have caused some concern. However, in my clinical opinion, the benefits of GLP-1s far outweigh the adverse effects for the majority of people living with type 2 diabetes or obesity. Now, to clarify, throughout this podcast, when I mention GLP-1 agonists, I’m referring to both GLP-1 agonists such as liraglutide, dulaglutide, and semaglutide, as well as tirzepatide, which is a dual GLP-GIP agonist.
Let me start with the commonest adverse effects we are likely to encounter with the GLP-1 agonists: gastrointestinal (GI) side effects. These include nausea, vomiting, diarrhea, constipation, abdominal pain, abdominal distension, dyspepsia, flatulence, and belching — a wide range of potential GI adverse effects.
These mostly occur during dose escalation, usually fade with time, and are typically mild to moderate in severity. GI side effects are dose-dependent, so we can consider slower dose escalation or drug holidays for those with particularly troublesome adverse effects. Because of these GI adverse effects, GLP-1 agonists should be used with caution in patients with severe GI disease such as inflammatory bowel disease and diabetic gastroparesis.
Strategies to discuss with patients to mitigate these GI side effects include counseling about eating habits, advising individuals to eat more slowly, eat only if really hungry, and to stop eating as soon as they feel full. Eating smaller portion sizes more frequently during the day, rather than larger meals two to three times daily as per tradition, and avoiding eating in the late evening or at night can all also help to reduce the incidence of GI adverse effects. Also, discussing diet composition can be helpful. Advise eating a low-fat diet, avoiding very sweet or spicy food, and keeping well hydrated, both with water-rich foods and fluid intake of at least 2 to 2.5 L daily of clear fluids, not including tea, coffee, or alcohol. For some individuals with disabling side effects, we can consider short-term use of proton pump inhibitors, antiemetics, laxatives, and antidiarrheal medications.
What other significant adverse effects of note do we need to be aware of in primary care? In the United Kingdom, warnings about severe acute pancreatitis, including rare reports of necrotizing and fatal pancreatitis, have been recently updated by the Medicines and Healthcare products Regulatory Agency (MHRA). We as clinicians are instructed to remain vigilant for signs and symptoms of acute pancreatitis in those on GLP-1 agonists and to advise patients to seek urgent medical attention if they develop severe and persistent abdominal pain that radiates to the back and sometimes is accompanied by nausea and vomiting.
If we do suspect pancreatitis, we must of course stop the GLP-1 agonist and we must not restart therapy if the diagnosis is confirmed. Overall, GLP-1 drugs should be used with caution in those with a history of pancreatitis, such as gallstone or alcohol-induced pancreatitis. Overall, though, pancreatitis is uncommon, and to put it in perspective, between 2007 and 2025 in the UK, there were 1296 cases of pancreatitis reported to the MHRA, of which 19 were fatal. This is on the background of over 25 million packs of GLP-1 agonist dispensed over just the past 5 years. It can be challenging to recognize pancreatitis in its early stages, as symptoms may be attributed to the GI side effects, as already discussed.
Next, hair loss. Hair loss can be a side effect of GLP-1 agonists, affecting up to 1 in 10 people taking these drugs. This is likely due to the phenomenon of telogen effluvium, which is a transient form of nonscarring hair loss occurring up to 3-4 months after a physiological or psychological trigger. The trigger in question here is the significant weight loss associated with GLP-1 agonists. Importantly, we must reassure patients that this hair loss is transient and reversible. Hair will regrow over the subsequent 3-6 months.
Next, nonarteritic anterior ischemic optic neuropathy (NAION). Again, in the UK, a recent warning has been issued about an increased risk for NAION, specifically with all forms of semaglutide (that is, Wegovy, Ozempic, and Rybelsus). NAION, for those unfamiliar with it, is a condition that causes a sudden deterioration in vision, usually in one eye. Patients typically describe sudden painless visual loss in one eye that is often described as a blurring or cloudiness of vision. NAION occurs due to reduced blood flow to the optic nerve. It is termed nonarteritic because this reduction in perfusion occurs without inflammation of the blood vessels, distinguishing it from arteritic causes. People living with type 2 diabetes are at an increased risk for NAION, and other risk factors include smoking, hypertension, and dyslipidemia.
NAION has been reported rarely in association with semaglutide for the treatment of type 2 diabetes, weight management, and cardiovascular risk reduction. Any individuals reporting a sudden loss of vision, including partial loss, on semaglutide should be referred urgently to ophthalmology for specialist assessment, and semaglutide should, of course, be stopped. We should be advising patients to seek urgent medical attention if they experience a sudden loss of vision or rapidly worsening eyesight on semaglutide.
Again, overall, NAION is very rare. Estimates suggest it may affect up to 1 in 10,000 people taking semaglutide. To put this in context, since 2018, there have been only three reports of NAION with semaglutide on the background of about 10 million packs of semaglutide dispensed over just the past 5 years.
Finally, let’s talk about GLP-1 agonist use in women using hormone replacement therapy (HRT). Now, all GLP-1 agonists delay gastric emptying, and therefore, there’s potential to impact the absorption of coadministered oral medications. However, no dose adjustments are required for most oral medications. If an individual is taking a narrow-therapeutic-index medication (for example, digoxin, lithium, or warfarin), closer monitoring may be warranted using our clinical judgment.
For women using HRT alongside GLP-1 agonists, there have been concerns about reduced absorption of any oral component of HRT, increasing the risk for endometrial cancer in these already high-risk women. In women living with overweight and obesity with comorbidities, including type 2 diabetes, transdermal estrogen is preferred, as it carries a negligible risk for venous thromboembolism. Thus, transdermal delivery of estrogen is preferred for women co-prescribed GLP-1 agonists.
Expert opinion from the British Menopause Society suggests that, pragmatically, it would be simplest to offer a nonoral route for the progestogen component of HRT for the duration of use of GLP-1 agonists. For example, a 52-mg levonorgestrel-releasing intrauterine device is recommended for endometrial protection in women using combined HRT alongside GLP-1 agonists, as it provides contraception in perimenopausal women and is unaffected by co-prescribed GLP-1 agonists.
For our patients who prefer to continue with oral HRT, expert opinion — again from the British Menopause Society — suggests temporarily increasing the dose of oral progestogen for 4 weeks after commencing a GLP-1 agonist and with each dose increase. Importantly, if there is evidence of unscheduled bleeding in women using HRT and GLP-1 agonists, we as clinicians may want to consider earlier investigation to exclude any endometrial pathology, as these women are at high risk of developing endometrial malignancy due to their risk factors of overweight, obesity, or type 2 diabetes.
To conclude, while I’ve highlighted a number of potential concerns with the GLP-1 agonists, I firmly believe the benefits of GLP-1s far outweigh the adverse effects for the majority of people living with type 2 diabetes or obesity.
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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: GLP-1 Adverse Effects: Practical Tips for Clinicians - Medscape - Mar 18, 2026.
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