Weight-loss injectables linked to GI problems

But Australian experts say the findings should be treated cautiously as the incidence is still low.

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The use of GLP-1 receptor agonists for weight loss has been associated with increased risk of pancreatitis, gastroparesis and bowel obstruction, a new study has revealed.

Australian experts have weighed in, however, saying the findings of the research letter, published in JAMA, should be considered with caution.

The researchers used information from a health database to compare potential side effects of glucagon-like peptide 1 receptor agonists liraglutide and semaglutide with bupropion-naltrexone, an obesity medication.

They found the GLP-1RAs were associated with almost four times the risk of stomach paralysis, nine times the risk of pancreatitis and four times the risk of bowel obstruction.

“Given the wide use of these drugs, these adverse events, although rare, must be considered by patients who are contemplating using the drugs for weight loss because the risk-benefit calculus for this group might differ from that of those who use them for diabetes,” the authors wrote.

“Limitations include that although all GLP-1 agonist users had a record for obesity without diabetes, whether GLP-1 agonists were all used for weight loss is uncertain.”

Sydney obesity doctor Dr Georgia Rigas, past chair of the RACGP Obesity Management Network, said the research letter should be interpreted “with caution”.

“Those already on anti-obesity treatment should not stop their medication, especially if they have no symptoms or side effects [but] should speak to their doctor if they have any concerns,” she said.

She said patients considering starting anti-obesity treatment should have an in-depth assessment and discussion with a doctor experienced in managing people living with overweight/obesity so that any recommendations are tailored to the patient’s individual health profile.

“Nothing we do/take or decide to not do/take is without risk,” Dr Rigas said.

“The key is patients need to be informed of what the medical evidence tells us, have it put it into context, with a goal to assist them in making an informed decision. Furthermore, [patients should be given] a list of ‘what to look out for’ and what to do about it if they develop symptoms during and out of office hours.

“As the incidence of these complications is low, we can still prescribe as is clinically indicated; however, as with all prescribed and over-the-counter preparations, we still need to remain vigilant.”

Endocrinologist Professor Gary Wittert, from the University of Adelaide, said the gastrointestinal adverse effects of GLP-1 receptor agonists were well documented in the clinical trials done to date.

“This analysis from a large health claims database confirms the increased risk, but it is rare. For example, pancreatitis occurred in 0.46% of users of semaglutide,” he said.

“The use of bupropion-naltrexone as a comparator is perplexing because compared to semaglutide it has a limited effect on weight.

“Furthermore, bupropion-naltrexone has its own set of adverse effects, and compared to GLP-1 receptor agonists, a far more limited benefit for glycaemia and there are no data showing cardiovascular or renal benefits.”

Associate Professor Priya Sumithran, from Monash University and the department of endocrinology and diabetes at Alfred Health, pointed out that the authors of the research letter had concluded that the adverse events must be considered by patients who were looking at using the medications for weight loss.

“In this study, it isn’t possible to be sure whether the medications were prescribed for weight loss,” she said.

“Regardless of whether medications are being prescribed for obesity, diabetes or other conditions, their risks and benefits should always be considered in relation to the goals and needs of the individual patient.”

Adjunct Research Professor of Nutrition at the University of South Australia Peter Clifton said the paper was a “timely reminder” of the potentially rare side effects of this drug class and he hoped it would lead to more research.

“Despite the very wide use of these drugs, the number of patients examined and the number of events are low and the confidence intervals very wide,” he said.

“Weekly semaglutide may cause fewer problems than daily liraglutide, but the duration of use is shorter. This research should prompt further examination of adverse event reporting in Australia.”

Dr Ian Musgrave, a senior lecturer in pharmacology at the University of Adelaide, said the findings would help clinicians prescribing these agents for weight loss.

“Any choice of pharmacological agent to assist with weight loss must be carefully considered, balancing benefits and side effects,” he said.

“For example, [while] naltrexone-bupropion has a lower incidence of serious gastrointestinal side effects compared to GLP-1 agonists, it also has side effects that must be carefully considered such as seizures, high blood pressure and suicidal thoughts or actions.”