ORAL glucagon-like peptide-1 receptor agonist (GLP-1RA) orforglipron has demonstrated meaningful weight loss and cardiometabolic improvements in patients without diabetes, according to clinical trial findings presented yesterday at the European Association for the Study of Diabetes (EASD) Annual Meeting 2025 in Vienna.
The Eli Lilly drug was previously reported to be effective in patients with diabetes (PD 23 Jun), and as an oral alternative to the injectable forms of GLP-1RA, such as Ozempic and Mounjaro, may be preferred by patients.
The trial included over 3,000 people with obesity, or overweight with a weight-related medical problem, who did not have diabetes.
Participants were allocated to receive one of three daily doses of the drug (6mg, 12mg and 36mg) or placebo, and unusually, the drug was given as an adjunct to exercise and a balanced, healthy diet rather than a reduced-calorie diet.
All three doses of the drug were effective for weight loss at 72 weeks compared with placebo, with those on the highest dose losing the most (an average of 12.4kg, or 12.4% of body weight) and those on the lowest dose losing an average of 8kg (or 7.8% body weight).
Additionally, among the 1,000 participants who had prediabetes at the start of the study, up to 91% of those taking the medication achieved near-normal blood sugar levels, compared with 42% of those taking placebo.
The most commonly reported adverse events were gastrointestinal-related – nausea, constipation, diarrhoea and vomiting – and generally mild-to-moderate in severity.
“People living with obesity have broad and varied needs – whether it’s improving weight, A1C, lipids, blood pressure, or other health markers that primary care physicians routinely address with their patients,” said Dr Kenneth Custer, President of Lilly Cardiometabolic Health.
“We’re encouraged to see orforglipron improve many of these areas in [the trial].
“As a convenient, once-daily pill that can be scaled globally, orforglipron could be ideally suited for early adoption in primary care, where proactive intervention has the potential to lead to meaningful, long-term health improvements.”
The findings have also been published in the NEJM HERE. KB
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