Research · PMID 37952131 · Landmark study
Reviewed by Neal Rouzier, MD, Preventive Medicine · Sep 2026
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes.
The New England journal of medicine · December 2023 · A Michael Lincoff, Kirstine Brown-Frandsen, Helen M Colhoun, John Deanfield, Scott S Emerson, et al.
What this study found
In patients with preexisting cardiovascular disease and overweight or obesity but without diabetes, weekly subcutaneous semaglutide at a dose of 2.4 mg was superior to placebo in reducing the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke at a mean follow-up of 39.8 m…
Why this trial matters
SELECT semaglutide obesity CVOT
How RAGMD uses this study
Clinical questions this paper informs
Synthesis lives on the evidence question — this page shows where the study sits in that analysis.
Primary study
Do GLP-1 receptor agonists reduce major cardiovascular events?
GLP-1 receptor agonists with cardiovascular outcome trials (including liraglutide and semaglutide in selected populations) reduce major adverse cardiovascular events beyond glucose lowering in high-risk patients with type 2 diabetes or obesity.
Open evidence analysisPrimary study
Can GLP-1 therapy be combined safely with hormone optimization regimens?
No large outcome trials specifically study combined GLP-1 and hormone therapy. Clinically, combinations are used with attention to muscle mass, nutritional status, and individual cardiometabolic goals.
Open evidence analysisSupporting literature
Is there a critical timing window for cardiovascular benefit from HRT?
The critical-window concept proposes that starting HRT closer to menopause may yield different cardiovascular effects than starting later. WHI subgroup analyses inform but do not prove this hypothesis for routine practice.
Open evidence analysisSupporting literature
Are bioidentical hormone preparations safer or more effective than conventional HRT?
FDA-approved bioidentical estradiol and progesterone have trial and post-marketing data. Custom-compounded bioidentical combinations lack equivalent efficacy and safety evidence and are not recommended over approved products by major societies.
Open evidence analysisSupporting literature
Does hormone therapy prevent cognitive decline or dementia?
WHI and subsequent analyses do not support HRT for dementia prevention when initiated in older postmenopausal women. Early-initiation cognitive studies are mixed and do not establish routine neuroprotection.
Open evidence analysisSupporting literature
Does menopausal hormone therapy prevent osteoporosis and fractures?
Estrogen-based therapy reduces bone loss and fracture risk in postmenopausal women, with benefit most established during early postmenopause. Guidelines support HRT for fracture prevention primarily when indicated for vasomotor symptoms or in high-risk women.
Open evidence analysisSupporting literature
How long should menopausal hormone therapy be continued?
Duration should be individualized based on symptom control, indication, and evolving risks. Many guidelines support continued use with annual reassessment rather than arbitrary stopping ages when benefits outweigh risks for that patient.
Open evidence analysisSupporting literature
Does GLP-1 treatment cause meaningful muscle loss?
GLP-1 therapies reduce weight through fat and lean mass loss; lean loss is partly proportional to total weight lost. Resistance training and adequate protein may mitigate but not eliminate lean mass decline.
Open evidence analysisSupporting literature
Do patients regain weight after stopping GLP-1 therapy?
Clinical trials and observational follow-up show substantial weight regain after GLP-1 discontinuation, suggesting chronic therapy may be needed to maintain benefit unless durable lifestyle changes are established.
Open evidence analysisSupporting literature
Do GLP-1 agonists increase pancreatitis risk?
Early signals raised pancreatitis concern, but large trials and post-marketing data have not confirmed a strong causal increase at population level. Caution remains reasonable in patients with prior pancreatitis.
Open evidence analysisSupporting literature
Do GLP-1 drugs increase thyroid cancer risk in humans?
Rodent C-cell tumor signals led to contraindications in medullary thyroid carcinoma and MEN2. Human epidemiologic data have not established a clear excess of thyroid cancer, but long-term surveillance continues.
Open evidence analysisSupporting literature
How does tirzepatide compare with semaglutide for weight loss?
Head-to-head trials suggest tirzepatide produces greater average weight loss than semaglutide at studied doses, with broadly similar gastrointestinal side-effect profiles. Long-term cardiovascular outcome comparisons are ongoing.
Open evidence analysisSupporting literature
Can resistance training and protein intake preserve muscle during GLP-1 weight loss?
Exercise and higher protein intake are biologically plausible strategies to attenuate lean mass loss during significant GLP-1-mediated weight reduction, though dedicated outcome trials are still emerging.
Open evidence analysis