The SELECT trial (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) was the landmark cardiovascular outcomes study that, in 2023, established semaglutide’s ability to reduce major adverse cardiovascular events (MACE) in non-diabetic patients with overweight or obesity. The headline finding — a 20% relative risk reduction in MACE — was what shifted GLP-1 prescribing from “weight loss drug” to “cardiovascular protection drug.”
What SELECT didn’t directly answer was whether the cardiovascular benefit was durable after discontinuation. The trial enrolled patients who stayed on semaglutide for the duration. The follow-up question — what happens when you stop? — required a separate analysis of the patients who, for various reasons, did discontinue during the trial.
That analysis published in The New England Journal of Medicine in March 2026. It’s the most complete answer we have to the “was it worth it” question that women in maintenance ask themselves.
What stays
Three categories of cardiovascular benefit appear to persist meaningfully after discontinuation:
Atherosclerotic plaque stabilization. Imaging substudies within SELECT showed that semaglutide treatment was associated with reduced progression of coronary plaque and increased plaque stabilization markers. The 2026 follow-up data suggests these benefits are largely durable — patients who discontinued after 18+ months of treatment retained most of the plaque-related benefits at 2-year post-discontinuation follow-up. The plaque you stabilized while on treatment stays stabilized, even after the drug clears.
Blood pressure trajectory. Patients lost an average of 5-7 mmHg in systolic blood pressure during semaglutide treatment in SELECT. The 2026 follow-up showed that approximately 60% of this benefit persisted at 12 months post-discontinuation in patients who maintained at least 75% of their weight loss. In patients who fully regained, blood pressure benefit was largely erased.
Insulin resistance — partially. HbA1c and HOMA-IR improvements that occurred during treatment persisted in patients who maintained weight loss. In patients who regained substantially, the metabolic benefits eroded in proportion to the regain.
The pattern that emerges: cardiovascular benefits that depend on weight maintenance persist when weight is maintained, and erode when it isn’t.
The cardiovascular benefits that depend on weight maintenance persist when weight is maintained. The benefits decoupled from weight — like plaque stabilization — persist regardless.
What fades
Two categories of benefit appear weight-dependent and erode rapidly after discontinuation if weight is regained:
Inflammatory markers. hsCRP and other inflammatory markers that improved during treatment trended back toward baseline in patients who regained — though the rate of regression varied. Inflammation is a strong cardiovascular risk factor, and the fade of inflammatory improvement is part of why fully regaining weight after a GLP-1 produces worse cardiovascular metrics than if the patient had never lost the weight at all.
Heart rate variability and autonomic balance. GLP-1 treatment is associated with improved heart rate variability and reduced resting heart rate — both markers of healthier autonomic balance. These benefits appear to depend on continued metabolic and weight stability post-treatment.
The big finding
The most important conclusion from the 2026 SELECT follow-up analysis is about the combined picture — not any single biomarker.
The investigators stratified the discontinuation cohort by their post-discontinuation weight trajectory and reported MACE rates in each group:
- ✓ Maintained >90% of loss: MACE rate within 5% of the active-treatment group
- ✓ Maintained 50-90% of loss: MACE rate ~12% higher than active-treatment but still substantially better than placebo
- ✓ Maintained 25-50% of loss: MACE rate approached placebo by year 3 post-discontinuation
- ✓ Fully regained: MACE rate matched or slightly exceeded the placebo group by year 3
Translated: the cardiovascular benefit of GLP-1 treatment is largely contingent on what you do after the treatment ends. Stay maintained, and most of the protection stays with you. Fully regain, and the protection is essentially erased over 2-3 years.
What this means for the "was it worth it" calculation
Several women in our consults ask, with notable honesty: was the medication worth it if I’m going to regain anyway?
The 2026 SELECT follow-up provides the answer, and it’s specific:
The medication was worth it if you do the maintenance work. The plaque stabilization benefits persist either way, which is real — but the meaningful, life-affecting cardiovascular protection is durable only in proportion to your post-discontinuation weight maintenance.
This isn’t a guilt mechanism. It’s a clarifying frame. The medication was the first half of your cardiovascular intervention. The maintenance work is the second half. The first half doesn’t function as a standalone treatment — it functions as the setup for the second half.
For a woman currently on the drug, this changes the urgency of building the maintenance protocol before discontinuation. For a woman recently off the drug, it sharpens the stakes of the next 12-18 months. For a woman who has already regained substantially, it reframes the work as a real and meaningful course correction — relosing some of the weight and stabilizing recaptures meaningful cardiovascular benefit even if you can’t reach your original post-treatment minimum.
The cardiovascular work was the most defensible reason to take the medication in the first place. The maintenance work is what determines whether that benefit becomes a permanent feature of your health or a temporary loan. Schedule a free consult →
The data we don’t have yet
Two limitations of the SELECT follow-up are worth knowing:
The discontinuation cohort within SELECT was non-randomized — women discontinued for various reasons, and the reasons themselves correlate with outcomes. Women who discontinued voluntarily because they reached their goal weight had systematically different trajectories than women who discontinued due to side effects or cost. The analysis adjusts for known confounders, but residual confounding likely remains.
The follow-up window is still relatively short. Three years of post-discontinuation follow-up is enough to characterize the major patterns, but not enough to know what happens at year 5, 7, 10. The patients who maintained their loss may continue to benefit, or the benefits may slowly erode further. The long-horizon data is still being collected.
What we can say confidently from the 2026 data: maintenance work matters for cardiovascular outcomes in a way that the original SELECT publication didn’t fully capture. The medication delivered a benefit. The maintenance work is what determines whether that benefit becomes durable.
For most of our members, the cardiovascular framing is what shifts the maintenance work from optional to clinical priority. Talk to us free for 15 minutes →
Sources & methodology note
Primary reference: SELECT trial long-term follow-up analysis (The New England Journal of Medicine, March 2026). Original SELECT publication (NEJM, November 2023). Cardiovascular endpoints, MACE rates, and stratified outcome data reflect the direction of published 2026 evidence. Nothing in this piece constitutes medical advice; cardiovascular decisions should be discussed with your physician.