GLP-1 Weight-Loss Jabs Linked to Rising Gallstone Disease and Gallbladder Surgery as Unapproved Retatrutide Fuels Black Market
核心洞察
A major 2022 analysis of 76 trials and over 103,000 patients found GLP-1 users were 37 percent more likely to develop gallbladder or bile duct problems.
NHS gallbladder operations reached 80,196 in 2024-25, the highest in a decade and a 15 percent rise year on year, with surgeons reporting weekly GLP-1 cases.
Retatrutide, an unapproved triple-agonist peptide, is being sold illegally online as a 'research chemical' while still in phase 3 trials.
Gallstones (搜索) are emerging as a clinically significant and increasingly common complication of GLP-1 weight-loss medications, with surgeons reporting a parallel surge in emergency gallbladder operations — while an unapproved triple-agonist peptide, retatrutide, circulates illegally in the UK ahead of any regulatory decision.
A major 2022 analysis of 76 clinical trials involving more than 103,000 patients found that those given GLP-1 drugs were 37 per cent more likely to develop gallbladder or bile duct problems than those receiving placebo or other treatment. The same analysis reported a 27 per cent higher likelihood of developing gallstones (搜索), a 36 per cent higher likelihood of gallbladder inflammation, and a 70 per cent higher likelihood of needing the gallbladder surgically removed. Critically, the risk appeared substantially greater when the drugs were used specifically for weight loss, where they are given at higher doses.
Surgical Burden Rises Alongside Prescribing
Official figures show more than 80,196 gallbladder operations were carried out by the NHS in 2024-25 — the highest number in the past decade and a 15 per cent increase on the previous year. Around 39,000 gallbladder removals were performed in England in 2000, meaning the number has more than doubled in 25 years.
"It's clear that GLP-1 medications affect gallbladder function and substantially increase the risk of gallstone disease," said Mr Saqib Rahman, consultant in general GI and emergency surgery at University Hospitals Southampton NHS Trust. "As an emergency gastrointestinal surgeon, it's something I now see quite a lot. We have multiple people a week coming in for emergency surgery who have been taking GLP-1s."
Mr Rahman added that while the absolute risk per patient remains modest, "the very large and growing number of people on these medications means the absolute number of patients presenting with biliary complications is substantial and rising."
Two Mechanisms Under Investigation
Experts attribute part of the link to the rapid weight loss these agents produce. "The overall guidance is that any type of weight loss — whether by surgery, medication or lifestyle — will increase the risk of gallstones (搜索)," said Dr Naveed Sattar, professor of metabolic medicine at the University of Glasgow. "This is because when you lose weight, you have a lot of cholesterol from fat material that has to go somewhere. And often it goes into and supersaturates the body's bile, which then creates gallstones."
Dr Sattar said the evidence so far suggests gallstones (搜索) "are probably not a specific effect of the GLP-1s, but are simply linked to the process of losing weight and having to get rid of that extra cholesterol."
Scientists have also investigated whether the drugs themselves alter gallbladder function. A 2018 trial by researchers in Copenhagen found that in patients taking liraglutide — the GLP-1 drug sold for weight loss as Saxenda — the gallbladder took significantly longer to reach maximum contraction after a meal. Slower emptying could allow bile to sit longer in the gallbladder, creating more opportunity for cholesterol to crystallise into stones. Mr Rahman noted that GLP-1s reduce hunger by slowing gastric emptying, which "also affects the gallbladder."
Case Report: Gallstone Attack After 6st Loss
The clinical picture is illustrated by the case of Kat Smith, a 41-year-old nurse and mother of three in London, who took Mounjaro for nearly two years and saw her weight fall from 14st 3lb to 7st 12lb, shedding more than 6st. She reported more energy, less breathlessness and improvements in cholesterol and blood pressure.
She later woke at 2am with chest pain so severe she believed she was having a heart attack. The pain spread from beneath her chest to her neck and arms, and within 20 minutes she could barely raise her left arm. "It's a pain that I've not experienced ever. Even childbirth pales in comparison," she said. Scans revealed a severe gallstone attack; she is currently waiting for surgery.
"One of the first questions she was asked by doctors was whether she was taking weight-loss medication. The gallstones (搜索), they told her, were almost certainly caused by the jabs. "I knew there were some side effects of the drug, but no one ever clarified to me that this could happen — or that I could end up in hospital in the worst pain of my life," she said.
Labeling and Company Positions
Gallstones (搜索) are a recognised potential side effect of GLP-1 weight-loss jabs, with patient safety information warning of the problem. The patient leaflet for Wegovy, which contains semaglutide, lists gallstones as a "common" side effect, meaning they may affect up to one in ten patients.
A spokesman for Mounjaro maker Eli Lilly said: "Patient safety is Lilly's top priority and we actively monitor, evaluate, and report safety information for all our medicines to the MHRA. Anyone experiencing side effects when taking any Lilly medicine should consult their doctor or other healthcare professional, and should ensure that they are getting genuine Lilly medicine."
A spokesman for Wegovy and Ozempic maker Novo Nordisk said GLP-1 drugs "are a well-established class of medicines, which have been studied rigorously in clinical trials." According to Novo Nordisk, acute gallstone disease was reported in 1.6 per cent of patients, leading to cholecystitis (搜索) in 0.6 per cent. "For this reason, acute gallstone disease is listed as a 'common' potential adverse reaction for Wegovy in the product's UK SMPC and should be considered when patients are being evaluated for this medicine," it said.
Risk Factors and Warning Signs
Women, people over 40, and those with a personal or family history of gallstones (搜索) are at greater baseline risk, and rapid or substantial weight loss can increase it further. Mr Rahman advised that "any sudden pain in the upper right or upper central abdomen, as well as pain that radiates to the right shoulder or centre of the back, should prompt assessment." Persistent nausea or vomiting beyond the expected GLP-1 side-effect window, and any fever, chills or yellowing of the eyes or skin, should also be cause for concern.
Both experts cautioned against patients abandoning the drugs. "In my perspective, these are very good drugs. But patients need to know their side effects," Mr Rahman said. Dr Sattar added: "Even if the risks are explained properly to patients, most people who are eligible will still choose to take them. But they need to be made clear in the first place."
Unapproved Retatrutide Fuels Grey-Market Supply
The safety debate is unfolding alongside a growing black market for GLP-1s and related peptides. Retatrutide — often called "Triple G" — is a synthetic peptide being developed by Eli Lilly that activates GLP-1, GIP and glucagon receptors, all three of which influence appetite, blood sugar and energy use. In clinical trials, the highest studied dose led to a mean weight reduction of 28.7 per cent at 68 weeks, the largest average loss reported for a weight-loss medicine to date.
Retatrutide is not yet approved by the MHRA and cannot be legally prescribed. Phase 3 trials are currently testing the drug for safety and effectiveness, and Eli Lilly plans to apply for official review with health regulators in early 2027.
Dr Jack Mosley, author of Food Noise, noted that while semaglutide acts on one receptor and tirzepatide on two, retatrutide acts on three and "can lead to even greater weight loss, comparable to bariatric surgery." He warned that the black market for GLP-1s is booming, with illicit copies of retatrutide sold from gyms, beauticians and TikTok. Some sellers exploit a regulatory grey area by marketing products as "research chemicals" that are "not for human consumption" while simultaneously giving injection instructions.
"If you are buying retatrutide at this point in 2026, you are buying an unlicensed and potentially dangerous version of the medication," Dr Mosley wrote. "You may be getting the wrong dose, a different version of the drug or in fact a different medication entirely." He cited multiple reports of people hospitalised after injecting insulin sold as GLP-1s, and others struck down by serious infections, with many counterfeit versions manufactured illegally in China, India and Russia.
One 55-year-old woman described in the source material sourcing retatrutide powder from a WhatsApp seller for £130 per four weeks — nearly £200 less per month than her Mounjaro costs after Eli Lilly raised UK prices in September, taking her 10mg pen from £150 to £300 a month. She reported severe fatigue, persistent dehydration and, during her first month, chronic left-sided abdominal pain that led to an overnight A&E visit and a diagnosis of suspected diverticulitis (搜索). She remains on the lowest dose after eight weeks, has neither lost nor gained weight, and plans to reorder.
Mr Rahman's guidance for clinicians remains that the drugs are effective but that side-effect counselling is essential. "Gallbladder issues are often trivialised. But if people have symptoms, they need to know to seek help," he said.