Orforglipron Cuts Weight by Up to 13.0% in Over-65s as Safety Questions Persist

8 articles · Updated · Medscape · May 13

Week-72 data from a post hoc ATTAIN analysis showed Eli Lilly’s oral GLP-1 orforglipron cut body weight by 7.9%-13.0% in adults 65 and older without diabetes and 7.5%-12.2% in those with type 2 diabetes, versus 1.6% and 2.3% with placebo.
Among 616 older participants, A1c fell 1.5%-1.7% in the diabetes trial versus 0.1% with placebo, and weight-loss results were broadly similar to the overall ATTAIN populations, helping address limited evidence in older adults.
Safety largely resembled that seen in younger patients, but adverse-event discontinuations were higher in older adults on orforglipron—5.2%, 17.0% and 13.7% across doses versus 5.5% on placebo—with mostly mild to moderate gastrointestinal side effects.
Possible lean-mass-loss events in over-65s ran at 6.0%-6.8% on orforglipron versus 4.3% on placebo, while cardiovascular, renal and death outcomes showed no clear treatment signal; six deaths were split evenly between drug and placebo groups.
The once-daily tablet may appeal to older patients because it avoids injections and fasting restrictions, but outside experts said the post hoc analysis was not designed to measure frailty, falls, sarcopenia or independence and called for dedicated trials.

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