One of the persistent open questions about GLP-1 receptor agonists has been whether the effect size shrinks in older adults. Lower lean body mass, slower metabolism, more co-morbidity, and a higher baseline rate of gastrointestinal complaints might plausibly blunt either the weight-loss response or the tolerability profile. A pooled analysis of the STEP program, presented by Prof Luca Busetto of the University of Padova at the European Congress on Obesity 2026 (ECO 2026, Istanbul, May 12–15), is the most directly relevant evidence to date on that question. It is not yet a peer-reviewed publication and should be read at that level of confidence — but the underlying STEP trials it pooled are themselves published, and the subgroup numbers are sizable.
This article summarizes what the analysis pooled, the headline findings, the safety signal that deserves attention, and where the boundaries of the evidence sit. It is informational and is not a substitute for personalized medical advice from a clinician who knows your history.
What the Analysis Pooled
The STEP (Semaglutide Treatment Effect in People with obesity) program is a set of randomized controlled trials of semaglutide 2.4 mg (the dose marketed as Wegovy in the United States) versus placebo, conducted by Novo Nordisk and published primarily in 2021–2024. The trials enrolled adults with obesity or overweight with a weight-related comorbidity, randomized them to semaglutide 2.4 mg weekly or placebo on top of a lifestyle intervention, and followed weight change over 68 weeks in most studies.
The Busetto pooled analysis aggregated data from STEP participants aged 65 and older. That yielded an analytic sample of 358 older adults — a meaningful subgroup, though small relative to the full STEP program. Endpoints included mean percent change in body weight at 68 weeks, proportions achieving ≥5%, ≥10%, and ≥15% weight loss, change in waist circumference, blood pressure, lipids, and glycated hemoglobin (HbA1c), and a safety summary including serious adverse events.
Headline Findings
- Mean weight loss at 68 weeks was −15.4% on semaglutide vs −5.1% on placebo — a placebo-adjusted difference of roughly 10 percentage points, consistent with the magnitude seen in the full STEP 1 trial population.
- Two-thirds of older participants on semaglutide achieved ≥10% weight loss.
- Nearly half achieved ≥15% weight loss.
- Reductions in waist circumference, systolic blood pressure, LDL cholesterol, triglycerides, and HbA1c paralleled the magnitude observed in younger STEP participants.
- The investigators concluded the response was "age-independent" — meaning the effect size in adults 65 and older was not detectably smaller than in younger adults within this pooled subgroup.
The Safety Signal
The detail that should be read carefully is the adverse-event summary. Serious adverse events occurred in 19.0% of the semaglutide arm versus 12.7% of placebo within the 65-and-older subgroup. That gap — roughly 6 percentage points — is consistent with the broader semaglutide tolerability profile, where gastrointestinal events (nausea, vomiting, diarrhea, constipation) and dehydration-related complications drive most of the burden. In an older population, the downstream risks of those events (acute kidney injury, fall risk, sarcopenia from inadequate oral intake) are higher than they are in younger adults.
The pooled analysis does not, on its own, provide enough granularity to characterize which specific serious adverse events drove the gap, or how they compare across the highest age strata (e.g., 65–74 vs 75+). That detail would need to come from the full peer-reviewed publication if and when it appears.
What This Does Not Show
- This is not a frailty or sarcopenia outcome study. Weight loss in older adults raises a separate concern about lean mass and bone density. STEP trials did not enroll frail older adults and did not powering for sarcopenia or fracture endpoints, so the pooled analysis cannot speak to those risks.
- This is not a cardiovascular outcomes trial. The cardiovascular benefit of semaglutide in adults without diabetes was established by the SELECT trial (Lincoff et al., NEJM 2023). SELECT enrolled a broader population including older adults, but the ECO 2026 pooled analysis itself is about weight and surrogate metabolic endpoints, not events.
- It is not yet peer reviewed. Congress presentations are an early-look format. Effect sizes can shift on final publication, and full safety tables typically expand with additional reviewer scrutiny.
- It is a pooled subgroup, not a dedicated older-adult RCT. A future dedicated trial in adults 65 and older — particularly one that captured body composition, functional fitness, and frailty endpoints — would carry more weight than a subgroup pull from trials designed primarily for a younger population.
How This Fits with Other Evidence
The pharmacokinetics of semaglutide were studied in older adults (Granhall et al., 2019) and did not show meaningfully different exposure or clearance versus younger adults — so a similar effect size at the same dose is biologically plausible. SELECT independently showed that semaglutide reduced major adverse cardiovascular events in a broad adult population with overweight or obesity and prior cardiovascular disease, including the older subgroup. The new STEP pooled analysis fills in the weight-loss-magnitude piece for the 65-and-older population at the standard 2.4 mg weekly dose.
What remains genuinely open: lean-mass preservation in older adults, the safety profile in adults 75 and older specifically, drug interactions in adults on multiple chronic medications, and the maintenance phase — what happens after the drug is stopped or paused. The STEP 4 trial (in younger adults) showed substantial regain after withdrawal, and there is no reason to expect that pattern would be different in older adults.
What People Considering Semaglutide Should Take From This
Three reasonable reads:
- The "older adults will not respond as well" assumption appears to be wrong at the weight-loss-magnitude level, at least within the 65-and-older subgroup of the STEP trials.
- The increased rate of serious adverse events in the older subgroup compared with placebo is a real signal and warrants careful tolerability monitoring and clinician follow-up — not a deterrent for everyone, but a reason to set the threshold for "let me know if you feel off" lower than you would in a 40-year-old.
- Lean-mass preservation, resistance training, and protein intake are not optional add-ons in this age group. The PeptideWise piece on GLP-1 and muscle preservation covers the protein-and-training side of the equation.
This article is informational and is not medical advice. Semaglutide is a prescription medication, and decisions about whether it is appropriate for any individual — particularly in older adults with multiple medications or chronic conditions — belong with a qualified clinician who knows the full picture.
The Bottom Line
The ECO 2026 STEP pooled analysis is the most directly relevant evidence to date on semaglutide 2.4 mg in adults aged 65 and older. The weight-loss magnitude looks comparable to the full STEP population, and the metabolic improvements track. The safety signal is meaningful and underlines why the older-adult conversation about GLP-1 therapy should be tolerability-first, with explicit attention to lean mass, hydration, and fall risk. The full peer-reviewed publication will sharpen the picture.