Plate Nº 66 · recorded October 14, 2026
Health & Medicine ResearchReported finding
SELECT Long-Term Weight Loss Data Published in Nature
Nature has published a long-term weight-loss analysis from the SELECT trial, examining semaglutide's effects in roughly 17,600 non-diabetic adults with obesity over a multi-year follow-up.
By Nathan Brooks3 min read639 words
In brief
- SELECT enrolled roughly 17,600 non-diabetic adults with obesity and cardiovascular disease
- Trial tested weekly 2.4 mg semaglutide against placebo over a median follow-up of about 40 months
- Primary 2023 NEJM report showed a 20% relative reduction in major cardiovascular events
- Nature paper focuses specifically on long-term weight-loss trajectories, not the cardiovascular endpoint
- Most prior weight-loss data came from 68-week STEP trials; SELECT followed participants for up to five years
A paper published in Nature focuses directly on long-term weight loss from semaglutide in adults with obesity who don't have diabetes, drawing on the SELECT cardiovascular outcomes trial.
The analysis, titled "Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial," joins a research program that has already reshaped how clinicians think about obesity medication.
What is the SELECT trial?
SELECT was a large, randomized, double-blind, placebo-controlled cardiovascular outcomes trial run by Novo Nordisk. It enrolled roughly 17,600 adults aged 45 and older with overweight or obesity (BMI of 27 or higher) plus established cardiovascular disease. Crucially, no participant had type 1 or type 2 diabetes at enrollment.
Participants received a weekly 2.4 mg injection of semaglutide — the same dose marketed as Wegovy — or a matching placebo. The primary endpoint was a composite of major adverse cardiovascular events: heart attack, stroke, or cardiovascular death.
The headline numbers, reported in the New England Journal of Medicine in December 2023: a 20% relative reduction in that composite endpoint over a median follow-up of about 40 months.
Why does a weight-loss paper matter?
Most published weight-loss data for semaglutide in non-diabetic adults comes from the STEP trials, which ran for 68 weeks. SELECT, by contrast, tracked participants for up to five years. That gives researchers a much longer lens on a question patients and payers keep asking: does the weight loss hold, plateau, or slowly drift back over years?
The new Nature paper appears positioned to answer parts of that question by tracking body-weight trajectories across the full SELECT follow-up. Until the complete data tables are public, specific figures — average kilograms lost at year three, share of participants losing 10% or more of baseline weight, post-discontinuation regain rates — should be treated as preliminary.
What does semaglutide actually do?
Semaglutide is a GLP-1 receptor agonist, a once-weekly injectable that mimics a gut hormone called glucagon-like peptide-1. GLP-1 slows stomach emptying, blunts appetite signals in the brain, and helps the pancreas release insulin after a meal.
In people with type 2 diabetes, the dominant effect is on blood sugar. In non-diabetic adults, the dominant effect is appetite suppression and weight loss. In the STEP weight-management trials, weekly 2.4 mg semaglutide produced average reductions of about 15% of baseline body weight at 68 weeks, versus roughly 2% on placebo.
How does weight tie into the cardiovascular benefit?
The December 2023 SELECT paper raised a subtle scientific question. The cardiovascular benefit showed up early, before big weight differences had built up. That pattern led some researchers to argue semaglutide's heart protection is at least partly independent of weight itself — possibly channeled through blood pressure, lipids, or direct effects on atherosclerotic plaque.
A multi-year weight analysis, which the Nature paper appears to provide, could sharpen that debate. If sustained weight loss tracks closely with cardiovascular benefit, weight is probably a major driver. If the cardiovascular signal runs ahead of weight changes, weight-independent mechanisms likely carry more of the load.
What's the practical takeaway?
For now, the cleanest summary is structural: SELECT, the largest and longest placebo-controlled trial of semaglutide in non-diabetic adults with obesity, has now produced a dedicated long-term weight-loss analysis in one of the most cited peer-reviewed journals in science.
Clinicians prescribing GLP-1 drugs for chronic weight management will be looking for two specific answers in the full paper: how durable average weight loss is beyond the 68-week STEP window, and how the curves compare between people who stayed on the drug and those who stopped. Both answers will shape whether insurers, providers, and patients treat these medications as long-term commitments rather than short-term weight tools.
via Google News: Clinical Trials (Source)
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Market editor covering companies, deals and strategy in general science news at SciBeat.
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