Age is one of the commonest reasons a clinician hesitates over these drugs, and the evidence behind that hesitation has been thin in both directions. A post hoc analysis worked through the SURMOUNT trials, including the three-year extension, along with SURMOUNT-OSA and SUMMIT, comparing participants aged 65 and over against those under 65 [1]. The related question of whether frailty changes the answer is covered in the frailty analysis.
The efficacy conclusion is that older participants did about as well as younger ones on weight, on cardiometabolic risk factors and on quality of life. No pooled number is attached to that: efficacy was analyzed study by study at whatever timepoint each trial used, so “broadly comparable” is the finding and there is no single figure to quote.
The safety list is more useful than the summary, because it shows what was actually examined. Gastrointestinal tolerability, falls, fractures, depression outcomes, pancreatitis, and renal, hepatic, gallbladder and biliary adverse events were each checked in the older group against placebo, and none showed a clinically meaningful difference. Falls and fractures appearing on that list matters, since those are the specific fears that attach to rapid weight loss in older people.
That boundary is where the observational evidence has to take over, with its own weaknesses. A cohort can include the frail and the very old in a way a trial never will, at the cost of never knowing who was chosen for treatment and why — the trade-off visible in the semaglutide and tirzepatide comparison and in the network meta-analysis of nineteen drugs.
One thing this analysis cannot reach at all is body composition over time in an age group that is already losing muscle without any drug. Trials measured weight; sarcopenia develops across years and is not a listed adverse event. That gap is the subject of what these drugs do to muscle, and it is the reason a reassuring safety list should not be read as a complete one.