GLP-1 drugs, marketed as weight-loss injections like Wegovy and Mounjaro, have been celebrated as a medical breakthrough, assisting millions in shedding weight and significantly reducing the risk of heart attack and stroke, often independently of weight loss. However, growing concerns about severe side-effects are prompting a re-evaluation of their safety profile.

New research published in *BMC Medicine* indicates that over 1.6 million adults in England, Wales, and Scotland used weight-loss drugs, including Wegovy and Mounjaro, between early 2024 and early 2025. This increasing usage is paralleled by a rise in anecdotal reports of patients presenting to A&E with persistent vomiting, dehydration, and more recently, complications such as gallbladder disease and acute pancreatitis. The Medicines and Healthcare products Regulatory Agency (MHRA) has updated its guidance to doctors and patients following a spike in reported fatalities linked to acute pancreatitis. The Yellow Card report scheme recorded 1,143 reports of acute and chronic pancreatitis, including 19 deaths, in GLP-1 users between 2007 and October 2025. A staggering 973 reports and 17 deaths occurred in 2025 alone, with most linked to tirzepatide (Mounjaro), and others to semaglutide (Ozempic, Wegovy), liraglutide (Saxenda), and dulaglutide. While acute pancreatitis is listed as an 'uncommon side-effect' in patient leaflets, the MHRA now highlights a 'small risk of severe acute pancreatitis' in its product information.

Another worrying trend is the increase in gallbladder removal operations performed by the NHS, which rose by nearly 15 percent from 69,745 in 2023-24 to 80,196 in 2024/25. Doctors attribute this surge to the increased use of GLP-1s, noting that rapid weight loss, a recognized side-effect, can lead to gallstone formation. When weight is lost quickly, the liver releases extra cholesterol into bile, and the gallbladder empties less often, causing bile to thicken and form stones. Gallstones, listed as a common side-effect affecting up to one in ten users, are concerning due to the speed and scale at which complications are now appearing. If gallstones block the pancreatic duct, they can trigger acute pancreatitis, which occurs in 3 to 7 percent of people who develop gallstones. Professor Ahmed Ahmed of Imperial College Healthcare Trust also suggests GLP-1 drugs may directly affect the pancreas, independent of weight loss.

In the US, numerous patients have filed lawsuits against GLP-1 drug manufacturers, claiming harm from severe side-effects they were not warned about, including vision loss. UK law firms report similar inquiries. The emergence of these more serious effects now follows a familiar pattern seen with past blockbuster drugs, where problems only become apparent once millions use them long-term. Clinical trials, designed to prove efficacy and detect common side-effects, are typically small and tightly controlled. For instance, major trials for Mounjaro involved only about 4,800 patients. Rarer harms, affecting patients with diverse underlying conditions, genetic dispositions, or those taking other medications, often only emerge when drugs are used more widely in the 'real world,' sometimes in ways not tested in trials, leading to different side-effect profiles.

Drug surveillance systems are struggling to keep pace with the rapid uptake of GLP-1s. The MHRA has issued dedicated, standalone guidance on these drugs, which will be revised as new risks are identified. A recent patient safety alert warned that semaglutide may, in very rare cases, cause sudden vision loss, specifically non-arteritic anterior ischemic optic neuropathy (NAION). The risk appears small, affecting up to one in 10,000 users, but patients are urged to seek urgent medical help if their sight changes suddenly. While the precise mechanism is unclear, it's thought that semaglutide’s rapid effects on blood sugar, blood pressure, and body weight may impact blood flow to the optic nerve. A 2024 *JAMA Ophthalmology* study found that type 2 diabetes patients on semaglutide had more than four times the risk of NAION, and overweight patients had over seven times the risk. Cameron Stephenson, a lawyer handling GLP-1 litigation in the US, highlights this as one of the most worrisome side-effects, often resulting in permanent vision loss. However, a major 2025 study in the *American Journal of Ophthalmology* involving 120,000 patients found no evidence that GLP-1 drugs increased the likelihood of NAION compared to non-users. Mike Burdon, a consultant ophthalmologist, points out that NAION is rare, and the overall benefits of GLP-1s in treating diabetes, reducing weight, and lowering hypertension risk may outweigh potential side-effects for many.

Complicating this risk-benefit assessment is the fact that the surge in GLP-1 use isn't always driven by medical necessity. Only a fraction of the 1.6 million UK users in the past year received them via the NHS. Dr. Oksana Pyzik of University College London warns that reliance on self-reported medical history, weight, BMI, and photographs – which are easily manipulated – combined with minimal or no follow-up, creates an 'unacceptably low bar for access.' This raises patient safety concerns, particularly for younger individuals influenced by social media trends and celebrity endorsements who may misreport eligibility or underestimate risks. Professor Judith Korner of Columbia University stresses the dangers for patients ordering these online without proper medical oversight, noting that individuals react differently and may require careful dose adjustments or cessation due to severe nausea, vomiting, or low blood sugar.

Concerns also extend to mental health, with some research suggesting GLP-1s could affect psychological well-being. People with psychiatric conditions are typically excluded from drug trials, leading to a lack of data on long-term consequences. A 2024 study in *Scientific Reports* found that GLP-1 users had nearly three times the risk of depression and double the risk of anxiety and suicidal behavior. Similar findings emerged from a 2024 *JAMA Network Open* analysis. One theory suggests GLP-1 receptors in the brain’s reward center might dampen dopamine effects. However, evidence is mixed; a 2025 review in *JAMA Psychiatry* found no evidence of worsened mental health in clinical trials. The FDA recently told Eli Lilly and Novo Nordisk to remove warnings about suicidal thoughts and behavior from drug labels, citing a study that found no increased risk. Despite this, concerns remain for psychologically vulnerable individuals, especially regarding potential relapse of negative thoughts and feelings upon stopping treatment without adequate support, and the suppression of symptoms in those with eating disorders without addressing underlying causes.

Drugmakers emphasize existing safety warnings. Novo Nordisk states that gallstone disease occurred in 1.6 percent of Wegovy trial patients and is listed as common, while Eli Lilly notes gallstones affect up to one in ten Mounjaro users for weight loss, and pancreatitis is uncommon. Both companies intend to defend against lawsuits, believing the allegations lack merit. Despite emerging concerns, doctors maintain that for the right patients, under proper medical supervision, GLP-1 drugs can be life-changing, especially for reducing cardiovascular risks. However, the benefits must always clearly outweigh the risks, necessitating careful individual patient assessment before prescribing.