Analyzing Known and New Side Effects of GLP-1 Drugs

As with any pharmaceutical, side effects are a reality, plain and simple.

With the meteoric rise and popularity of GLP-1 therapies, used both by those who meet the medical criteria and by people seeking to lose the last few pounds, it’s important to understand potential side effects in considering whether they may be right for you.

Let’s start with the side effects that have been identified since GLP-1 drugs were first tested in clinical trials.

• Gallbladder Concerns: Patients taking GLP-1 drugs seem to have a higher risk of gallbladder disease, including developing gallstones. Often, this is related to a very restricted diet, slowing the movement of bile through the gallbladder. Slower gallbladder motility causes the bile secretions to coagulate and form stones over time.
• Pancreatitis: Closely linked to gallbladder health is that of the pancreas. Some patients taking GLP-1 receptor agonists (GLP-1 RAs) may experience inflammation of the pancreas, known as pancreatitis. Pancreatitis is a serious condition that requires urgent medical attention and stopping the GLP-1 medication.
• Gastroparesis: This is a motility issue in which food does not pass from the stomach into the small intestine as quickly as it should. There is some debate as to whether GLP-1 meds cause gastroparesis or if they simply worsen an existing predisposition to the condition. Regardless, gastroparesis can be very uncomfortable and increase the risk of bacterial growth within the stomach, posing concerns for patients preparing for surgery. For this reason, GLP-1 medications are typically stopped at least two weeks before any procedure. In rare cases, patients have experienced longer-term gastroparesis even after discontinuing the medication.

Side effects discovered since FDA approval

Because clinical trials can only include a limited number of participants, they don’t always capture every possible side effect of a new medication. With the widespread use of GLP-1 drugs, additional adverse reactions have emerged, or have been strongly suspected, since their approval for weight loss. Some post-clinical trial side effects include:

• Depression and anxiety: There is ongoing debate about whether GLP-1 medications directly cause symptoms of depression and anxiety, or if these issues are more closely tied to the significant lifestyle and body changes that accompany rapid weight loss. Still, there is evidence of patients reporting depression and related mental health conditions after starting GLP-1 therapies. There are also claims showing the opposite effect, which could also make sense.
• Suicidal ideation: Although not well studied, there have been reports of suicidal thoughts in patients taking GLP-1 medications. It remains unclear whether the drugs themselves trigger these thoughts or if they exacerbate an existing predisposition or underlying mental health condition.
• Muscle mass and bone density: While GLP-1 receptor agonists are not necessarily the cause, patients can experience significant weight loss, which, in turn, increases the risk of muscle mass and bone density loss. The reasoning is two-fold:
  • First, some weight loss programs, especially those offered online, lack adequate guidance on nutrition and exercise protocols for achieving significant weight loss.
  • Second, patients often underestimate the importance of lifestyle support, including a multivitamin, sufficient protein, and strength training, to build and maintain muscle mass. Without these measures, rapid weight loss may come more from muscle than fat, which helps explain why some studies suggest up to 60% of GLP-1–related weight loss may actually involve lean tissue.¹ Encouragingly, new medications are being developed to address these concerns and used in conjunction with lifestyle modifications.
• Ocular degeneration: A new report from the American Optometric Association has found that GLP-1 RA use is being linked to rare but serious ocular complications. The most notable is non-arteritic anterior ischemic optic neuropathy (NAION), a condition that can lead to sudden, permanent vision loss, though it occurs in only a very small fraction of patients, estimated at up to 1 in 10,000. GLP-1 RAs designed for weight loss may also worsen diabetic retinopathy and possibly exacerbate age-related macular degeneration. Experts recommend that patients, especially those with diabetes or existing eye disease, receive a comprehensive dilated eye exam within a year before or within one month after starting therapy, along with regular follow-ups and coordinated care between optometrists and prescribing clinicians.²
• Dermatologic reactions: GLP-1 RAs are increasingly recognized for their complex relationship with skin health, with dermatologic reactions ranging from mild irritation to more serious immune-mediated conditions. Reported side effects include injection-site reactions, rashes, itching, hives, angioedema, and hypersensitivity responses, as well as rare autoimmune conditions such as bullous pemphigoid. On the other hand, GLP-1 RAs may improve certain inflammatory skin diseases, including psoriasis and hidradenitis suppurativa, by reducing pro-inflammatory cytokines. Most reactions resolve without intervention, but persistent or severe symptoms should be evaluated by a clinician, as they may require discontinuation or modification of therapy.³

Unfortunately, many patients see GLP-1 medications as a quick fix and neglect the critical role of medical supervision, diet, and exercise.

Duration of use

A recent 2025 study found that most patients on older-generation GLP-1 drugs regained their lost weight and returned to baseline within a year of stopping treatment. Even those on newer GLP-1 medications, such as semaglutide and tirzepatide, typically regained weight after discontinuing the drug.⁴ It’s looking like these drugs may only be effective while patients continue taking them, with few exceptions.

Using GLP-1 medications without proper lifestyle changes is not recommended, and may require long-term or even indefinite use. And the reality is, we still don’t fully understand the long-term side effects of such extended treatment.

Balancing benefits and risks

The list of potential side effects with GLP-1 medications should raise questions – but that doesn’t mean these drugs should be dismissed outright. The mild side effects typically resolve on their own, and the more severe ones are reported as very rare. Discussing them openly ensures that patients understand that every treatment decision comes down to weighing the risks against the benefits. For this reason, GLP-1 medications are typically reserved for patients with obesity or significant excess weight, where the potential benefits are life-changing and, in many cases, lifesaving.

For these patients, GLP-1 medications can improve blood sugar control, reduce cardiovascular risks, and support substantial, sustainable weight loss. The balance tips differently, however, for individuals using these drugs off-label to lose only a small amount of weight. In such cases, the risks may outweigh the rewards, especially if side effects interrupt quality of life.

GLP-1 medications have also shown promise when paired with bariatric surgery. Before surgery, they may help shrink the liver, making the procedure safer. After surgery, they can be used strategically to help patients who are struggling with weight regain, potentially reducing the need for revisional procedures.

The bottom line is that no medication is a magic bullet. Long-term success requires more than a prescription. Lifestyle habits (especially a balanced diet, regular physical activity, and consistent follow-up care) remain the foundation for maintaining weight loss.

Starting with an experienced weight loss team, such as ours, provides patients with the best opportunity to customize their plan and lock in the progress they’ve worked so hard to achieve. Whether you’ve already tried GLP-1 RA medications, are curious about them, or have questions about GLP-1 therapy versus weight loss surgery, MIIS Weight Loss Institute is here to help guide you to the best solution for your individual needs.

1. Neeland, I. J., Linge, J., & Birkenfeld, A. L. (2024). Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. Diabetes, obesity & metabolism, 26 Suppl 4, 16–27. https://doi.org/10.1111/dom.15728. 
2. American Optometric Association. (2025, July 10). GLP-1 Receptor Agonists and vision risk. Aoa.org. https://www.aoa.org/news/clinical-eye-care/public-health/glp-1-receptor-agonists-and-vision-risk. 
3. Persson, C., Eaton, A., & Mayrovitz, H. N. (2025). A Closer Look at the Dermatological Profile of GLP-1 Agonists. Diseases (Basel, Switzerland), 13(5), 127. https://doi.org/10.3390/diseases13050127.
4. Quarenghi, M., Capelli, S., Galligani, G., Giana, A., Preatoni, G., & Turri Quarenghi, R. (2025). Weight Regain After Liraglutide, Semaglutide or Tirzepatide Interruption: A Narrative Review of Randomized Studies. Journal of clinical medicine, 14(11), 3791. https://doi.org/10.3390/jcm14113791.