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Patients who took popular weight loss drugs were 12 per cent less likely to develop Alzheimer’s disease but were more at risk of arthritic, kidney and pancreatic disorders, according to the largest ever study of the medicines’ widening impact.
A cohort of 215,000 US military veterans with diabetes who used so-called GLP-1 treatments showed lower health risk for 42 condition and a higher risk for 19 others, compared with those who took older medicines.
The analysis of 2.4mn patients bolsters research into how blockbuster drugs for obesity and diabetes such as Novo Nordisk’s Ozempic and Wegovy and Eli Lilly’s Mounjaro could have significant effects on other health conditions.
The findings of the six-year study, which used health data from the US veterans affairs department, were published on Monday in Nature Medicine.
Researchers at Washington University in St Louis compared 175 health outcomes in people treated with GLP-1 with those who took other diabetes drugs. Ziyad Al-Aly, the study leader, said they were inspired by the new drugs’ “skyrocketing popularity”, with one in eight Americans reported to have taken them.
“It is important to systematically examine their effects on all body systems . . . to understand what they do,” he said.
The researchers found widespread benefits for cognitive and behavioural health including a lower risk of developing Alzheimer’s, which has become a big focus of GLP-1 research in clinical trials.
“The 12 per cent reduction we found may seem like a weak effect but it is teaching us about the biology of Alzheimer’s disease,” Al-Aly said. GLP-1s could enhance the effect of treatments that target the build-up of toxic amyloid protein in the brain, he added.
Sir Stephen O’Rahilly, a professor of clinical biochemistry at Cambridge university who was not involved in the study, said the results had to be interpreted cautiously, as the data was based on observations rather than a clinical trial and was “heavily skewed to older white males.”
But he added that “the study provides useful reassurance about the safety of this class of drugs”.
GLP-1 drugs work in two ways. One is indirect — reducing the effects of diabetes and obesity. The other is direct enhancement of the activity of glucagon-like peptide 1, a hormone that works on cells throughout the body and plays several biological roles beyond regulating blood sugar levels.
“What stood out for me in our results is the consistent effect on curbing addiction disorders,” said Al-Aly. “There is a school of thought that obesity is the result of food addiction.”
Altogether the GLP-1 group did better on 42 health outcomes, ranging from cardiovascular disease to bacterial infections. Most of the benefits were relatively modest, with risk reductions in the 10-20 per cent range.
“However the modest effect does not negate the potential value of these drugs, especially where few effective treatment options exist,” said Al-Aly.
On the downside, GLP-1s made 19 disorders more likely. A surprising finding was an 11 per cent increase in the risk of arthritis, even though loss of excessive weight might be expected to reduce joint pain and swelling.
But the most significant adverse effects identified by the study were on the pancreas and kidneys.
Extensive research is required before GLP-1 drugs could be widely prescribed to people who are not suffering from diabetes and obesity, Al-Aly said: “Our findings underscore the possibility for wider applications but also highlight important risks that should be carefully monitored.”
Novo Nordisk said it “welcomes independent research investigating the safety, efficacy and clinical utility of our products”, adding that research so far had shown a “reassuring safety profile” for semaglutide, the active ingredient in its Ozempic diabetes and Wegovy weight-loss treatments.
US prices for Ozempic and Wegovy could be heavily cut after President Joe Biden’s outgoing administration included them in the next round of Medicare negotiations.
