GLP-1 receptor agonist use in adults age 65 and older is expanding rapidly as Medicare Part D plans add semaglutide and tirzepatide for cardiovascular and obesity indications, yet dedicated geriatric randomized trials remain rare. The strongest age-specific data come from prespecified subgroup analyses of large cardiovascular and heart-failure trials — STEP-HFpEF across the age spectrum, SUSTAIN 6 and PIONEER 6 stratified by baseline age, and SELECT hospitalization analyses — supplemented by a growing set of meta-analyses and narrative reviews focused on sarcopenic obesity, lean-mass preservation, and frailty. The papers below are ranked by clinical and policy impact for the geriatric population. None of the trials below were designed primarily as geriatric trials; readers should interpret findings as subgroup or post hoc evidence unless otherwise noted.
Ranked papers
#1STEP-HFpEF (age subgroup)
Pandey A, Moroney M, Verma S, et al. · Eur J Heart Fail · 2025
Primary endpoint: Change in KCCQ-CSS, six-minute walk distance, and body weight by age stratum
This prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials examined semaglutide 2.4 mg in 1,145 adults with obesity-related heart failure with preserved ejection fraction stratified by age (<65, 65-74, ≥75 years). Improvements in KCCQ-CSS, six-minute walk distance, and body weight were consistent across all three strata, including the oldest group. Safety signals did not differ by age. The analysis is currently the strongest randomized evidence that semaglutide retains efficacy and tolerability in adults 75 and older with HFpEF and obesity.
PMID 41290376 ↗DOI 10.1002/ejhf.70049 ↗
#2SUSTAIN 6 + PIONEER 6 (age subgroup)
Bain SC, Belmar N, Hoff ST, et al. · Diabetes Ther · 2025
Primary endpoint: Three-point MACE, HbA1c, body weight, and adverse events by baseline age
This post hoc pooled analysis of the SUSTAIN 6 (injectable semaglutide) and PIONEER 6 (oral semaglutide) cardiovascular outcomes trials stratified outcomes by baseline age (<65, 65-74, ≥75 years) across 6,480 type 2 diabetes participants. Three-point MACE reduction, HbA1c change, and weight loss were broadly consistent across age strata, with no signal of excess adverse events in the oldest group. The paper is the most rigorous semaglutide age-stratified safety analysis in the cardiovascular-outcomes literature.
PMID 39520501 ↗DOI 10.1007/s13300-024-01659-7 ↗
#3
Rego de Figueiredo I, Simas FS, Ghiletchi A, et al. · Obesity (Silver Spring) · 2026
Primary endpoint: Pooled weight loss, A1C, and adverse events in adults age 65+
A 2026 meta-analysis pooling randomized and observational studies of GLP-1 receptor agonists restricted to participants age 65 and older with obesity. The analysis quantified pooled weight loss, glycemic effects, and adverse-event profiles in the geriatric population, finding efficacy magnitudes comparable to general-adult trials but with somewhat higher rates of gastrointestinal discontinuation. The paper synthesizes the scattered elderly-subgroup evidence into a single effect estimate clinicians can cite when counseling Medicare patients.
PMID 41640092 ↗DOI 10.1002/oby.70098 ↗
#4
Alexander GC, Xiao X, Dilek S, et al. · JAMA Intern Med · 2026
Primary endpoint: Heterogeneity of weight-loss effect by age, sex, race, baseline BMI
This 2026 JAMA Internal Medicine systematic review and meta-analysis examined whether weight-loss effects of GLP-1 receptor agonists vary across demographic subgroups, including age strata. The analysis found broadly consistent relative weight loss across age groups but smaller absolute reductions in older participants, partly explained by lower baseline weight. The paper is the most current peer-reviewed quantification of how age modifies GLP-1 weight-loss response and is widely cited in 2026 prescribing guidance.
PMID 41770554 ↗DOI 10.1001/jamainternmed.2025.8222 ↗
#5
Prokopidis K, Daly RM, Suetta C · J Nutr Health Aging · 2025
Primary endpoint: Narrative review of sarcopenic obesity risk with GLP-1 therapy
A 2025 narrative review focused on whether GLP-1-induced weight loss in older adults disproportionately reduces skeletal muscle and worsens sarcopenic obesity. The authors synthesize body-composition data from the STEP, SURMOUNT, and SUSTAIN programs and conclude that 25-40% of total weight lost is lean tissue — a magnitude that may be clinically meaningful in adults with pre-existing low muscle mass. The paper outlines screening criteria and resistance-exercise plus protein-intake mitigation strategies, and is one of the most-cited 2025 references on the topic.
PMID 40819408 ↗DOI 10.1016/j.jnha.2025.100652 ↗
#6
Chen AS, Batsis JA · Diabetes · 2025
Primary endpoint: Conceptual review of incretin therapy in sarcopenic obesity
Published in the ADA journal Diabetes, this 2025 perspective from Batsis (a geriatric obesity-medicine clinician-researcher) frames the central tension of GLP-1 use in older adults: cardiometabolic benefit must be weighed against accelerated lean-mass loss in patients already at risk for sarcopenia. The paper proposes a clinical algorithm incorporating handgrip strength, gait speed, and DXA when available before initiating incretin therapy in adults 65 and older, and discusses the evidence gap for dedicated geriatric trials.
PMID 40644314 ↗DOI 10.2337/dbi25-0004 ↗
#7
Scheen AJ · Diabetes Metab · 2026
Primary endpoint: Editorial review of sarcopenia risk in special populations
A 2026 editorial review by André Scheen explicitly identifies older adults, frail patients, and those with chronic kidney disease as the three populations where GLP-1-induced lean-mass loss is most likely to cross from cosmetic concern to clinical harm. The paper calls for dedicated trials in these subgroups and for body-composition endpoints to become standard in obesity pharmacotherapy development. Cited frequently in 2026 European guideline discussions.
PMID 41101588 ↗DOI 10.1016/j.diabet.2025.101708 ↗
#8
Moscucci F, Baratta F, Pastori D, et al. · Nutrients · 2026
Primary endpoint: Narrative review of postmenopausal weight loss with GLP-1 therapy
This 2026 narrative review focuses specifically on postmenopausal and older women, who account for a disproportionate share of Medicare-age GLP-1 prescriptions. The authors discuss sex-specific differences in body composition response to semaglutide and tirzepatide, the interaction with estrogen loss and bone density, and a structured protein and resistance-training protocol intended to minimize lean-mass loss. Useful clinical reference for clinicians managing women aged 60 and older on GLP-1 therapy.
PMID 41754149 ↗DOI 10.3390/nu18040632 ↗
#9
Toma L, Buckley K, Early N · Sr Care Pharm · 2026
Primary endpoint: Case-based pharmacotherapy review
Published in The Senior Care Pharmacist (the journal of the American Society of Consultant Pharmacists), this 2026 case series walks through GLP-1 prescribing decisions in older adults with polypharmacy, declining renal function, and Beers Criteria comedications. The cases cover dose-titration adjustments, drug-interaction screening, and discontinuation triggers (unintended weight loss below ideal body weight, frailty progression). One of the few practical, pharmacist-authored geriatric GLP-1 references available in 2026.
PMID 41966038 ↗DOI 10.4140/TCP.n.2026.78 ↗
#10SELECT (hospitalizations analysis)
Nicholls SJ, Ryan DH, Deanfield J, et al. · JAMA Cardiol · 2026
Primary endpoint: All-cause and cause-specific hospitalizations
An exploratory analysis of SELECT examining hospitalizations across the 17,604 adults with established cardiovascular disease and obesity randomized to semaglutide 2.4 mg or placebo. Mean age was 61.6 years and roughly one-third of participants were 65 or older. Semaglutide reduced all-cause hospitalization rates and was particularly notable for reductions in cardiovascular hospitalizations — a healthcare-utilization endpoint directly relevant to Medicare and integrated-health-system payers evaluating GLP-1 coverage policy for older adults.
PMID 41433034 ↗NCT03574597 ↗DOI 10.1001/jamacardio.2025.4824 ↗
About this list
We curate ranked, citation-anchored PubMed paper lists for the most-searched questions in obesity medicine. Every citation on this page was checked against PubMed on 2026-05-28. Each paper card links directly to PubMed and to ClinicalTrials.gov where applicable.
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