Weight-loss drugs like Ozempic may offer health benefits far beyond those already flagged by research, a large-scale study suggests.

Scientists probing the health records of nearly 216,000 people with diabetes who took the GLP-1 receptor antagonists found they had a lower risk of 42 conditions than people on other forms of treatment. They also had a higher risk of 19 health problems.

Some results, like reduced risk of cardiovascular disease and increased chance of nausea and vomiting, were expected. But others, like a lower risk of bacterial infection and an increased chance of joint pain, took researchers by suprise.

Some surprising observations included an 18% percent lower risk of psychotic disorders like schizophrenia and a 12% lower chance of Alzheimer’s. Worse outcomes included a greater risk of low blood pressure and joint pain.

The full list of results can be found in the journal Nature Medicine, where the research was published Monday.

‘Mapping’ Weight-Loss Drugs

Researchers wanted to comprehensively “map” the health outcomes of people using weight-loss drugs. To this end, they compared 175 health outcomes of 215,970 patients using GLP-1 RA drugs with those of 536,068 patients on certain other diabetes drugs and those of 1,203,097 patients on a standard care regime.

All patients in the study had diabetes, but “there is no biologic or clinical reason to think that the beneficial and risk profiles would be very different in people without diabetes,” Dr Ziyad Al-Aly, a co-author of the research from Washington University in St Louis, told The Guardian.

The participants were all obese — something that would likely affect the level of benefit weight-loss drugs can offer.

Weight-Loss Drug Study Offers Limited Evidence

Although the weight-loss drug study involves a very large number of participants, its design means its evidence is fundamentally limited. That’s because the study is observational, which means it’s at risk of “confounding” by factors researchers simply haven’t measured.

Scientists consider randomized controlled trials, where participants are anonymised and randomly given either a treatment or a placebo, the “gold standard” of evidence-based medicine. These studies do their best to eliminate variables that could distort the real impacts of a drug.

Sir Stephen O’Rahilly, professor of clinical biochemistry at the University of Cambridge explained the study should be interpreted “very cautiously” as participants “have not been randomly allocated to GLP-1 receptor agonist treatment.”

“So any difference between those taking and not taking the class of drug could potentially be attributable to factors other than the drug,” he said. O’Rahilly was not involved in the research.

Naveed Sattar, professor of cardiometabolic medicine at the University of Glasgow, said the results “cannot be considered anywhere near definitive.” Nor would it generally be used to influence clinical guidelines, he said.

“A few of the suggested benefits have been confirmed in randomized trials,”the scientist, who was also not involved in the study. But “most others require future assessment to confirm or refute.”

Those looking for stronger evidence about the risks and benefits of the drugs will have to wait for the results of large-scale gold standard trials, several of which are underway.

But both Satter and O’Rahilly agree the study offers insight into the safety profile of weight-loss drugs, which have previously been linked to very rare but concerning potential risk of suicidal thoughts and even death. The results are “reassuring regarding the risk/benefit ratio for the long term use of GLP-1 receptor agonists in people with diabetes,” O’Rahilly said.

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