Explainer · Heart & Metabolic
Heart benefit of GLP-1 drugs faded after people stopped, in 333,687 US veterans with type 2 diabetes
Many people stop GLP-1 drugs within a year. In a large study of veterans, the heart protection built up with continued use and eroded month by month after treatment stopped.
- An observational study of 132,551 people starting GLP-1 drugs and 201,136 starting sulfonylureas, followed for three years.
- All had type 2 diabetes and were US veterans, mostly older men.
- Staying on a GLP-1 drug for the full three years went with 18% lower risk of heart attack, stroke or death.
- Half a year off treatment went with 4% higher risk than staying on, rising to 22% after two years off.
- People who stop differ from those who continue, so this cannot prove stopping causes the extra risk.
GLP-1 drugs (glucagon-like peptide 1 receptor agonists, the class that includes semaglutide) are prescribed for blood sugar and weight, and large trials have also shown they protect the heart. What those trials did not answer is what happens when people stop. Stopping happens for all sorts of reasons: cost, side effects, supply problems, or a sense that the job is done.
A study in BMJ Medicine (a journal from the publisher of The BMJ) followed 333,687 US veterans with type 2 diabetes for three years and compared what happened under 16 different patterns of use. The heart benefit built up the longer people stayed on treatment, and it drained away after they stopped.
What GLP-1 drugs do
MedlinePlus explains that diabetes is a disease in which your blood glucose, or blood sugar, levels are too high, and that with type 2 diabetes, your body does not make or use insulin well. GLP-1 receptor agonists, given mostly by injection, are one such class; they slow digestion, curb appetite and help the body release insulin when blood sugar rises.
Their effect on the heart is part of why they are prescribed. Trials in people with diabetes have shown fewer heart attacks and strokes. Previously, what happened to that protection when people stopped was unknown, which is the question the authors set out to answer.
How the GLP-1 discontinuation study worked
The researchers used a method called target trial emulation, which sets out the rules of a hypothetical trial and then applies them to health records. They drew on electronic healthcare databases of US Department of Veterans Affairs, 1 January 2017 to 31 December 2023.
Two groups were compared: 132,551 people starting a GLP-1 drug and 201,136 starting a sulfonylurea, an older diabetes tablet. In the GLP-1RA arm, treatment status was reassigned every six months, generating 16 prespecified treatment strategies that varied in how long people continued, stopped or interrupted treatment. The outcome was heart attack, stroke or death within three years.
What happened when people stopped
Length of use mattered. Participants who continued to use GLP-1RAs for the whole three year follow-up period had the most pronounced risk reduction compared with the sulfonylurea group: about 18% lower risk of heart attack, stroke or death. People who used the drugs for six months, a year or 18 months and then stopped ended up no better off than the comparison group.
Stopping carried its own signal. Compared with continued use of GLP-1RA, discontinuing treatment for 0.5 years was associated with an increased risk of major adverse cardiovascular events, about 4% higher, and the gap widened with time: 14% higher at one year off and 22% higher at two years. Interrupting treatment and restarting showed a similar pattern.
Why staying on a GLP-1 drug matters
The authors read this as a benefit that has to be maintained. They conclude that the cardiovascular benefit of GLP-1RAs accumulated with continuous use, but even brief periods of discontinuations or interruptions might progressively erode that protection.
That matters because stopping is common. If the heart protection depends on staying on treatment, then cost, coverage gaps and supply shortages are not just inconveniences; they may erase the benefit people started the drug for. It also reframes these medicines as long-term treatment rather than a short course.
What a records-based GLP-1 study cannot prove
People who stop a drug differ from people who keep taking it. They may have more side effects, less money, other illnesses or worse access to care, and although the analysis adjusted for many factors, the authors say residual confounding cannot be completely ruled out.
The cohort was US veterans, who are older and mostly men, so the numbers may not carry over to everyone. Prescription records show what was dispensed rather than what was taken. The analysis also grouped all GLP-1 drugs together, nearly all of them injectable, and did not compare individual drugs or oral versions. The study protocol was not pre-registered.
What this changes for people on GLP-1 drugs
For anyone taking one of these drugs for type 2 diabetes, the practical message is to treat gaps in supply or coverage as worth solving rather than riding out. If side effects or cost are the obstacle, a doctor may be able to adjust the dose or switch the drug.
Nobody should stop a prescription because of a headline, and nobody should start one for heart protection alone on the strength of an observational study. The randomized trials remain the stronger evidence that these drugs help the heart; this analysis suggests the benefit does not stay behind once the injections stop.
People also ask
What did the study find?
Compared with sulfonylureas, people who used GLP-1 drugs for the whole three years had an incidence risk ratio of 0.82 (95% CI 0.78 to 0.85) for heart attack, stroke or death. Compared with continued use, stopping for half a year carried a risk ratio of 1.04 (1.01 to 1.08), rising to 1.14 (1.09 to 1.18) at one year and 1.22 (1.16 to 1.27) at two years off.
What is a target trial emulation?
A way of analyzing existing health records as if they were a randomized trial: the researchers specify eligibility, treatment strategies and outcomes in advance, then compare groups that follow each strategy. It removes some biases but cannot remove them all.
What is a major adverse cardiovascular event?
In this study, a heart attack, a stroke, or death from any cause.
Does short-term use do nothing?
In this analysis, people who used a GLP-1 drug for six months to a year and a half and then stopped ended up with about the same three-year risk as those on sulfonylureas. The benefit built up with longer continued use.
Why do people stop these drugs?
Cost and insurance coverage, side effects such as nausea, shortages, and reaching a weight goal are all common reasons. This study did not analyze why people stopped.
Should I keep taking my GLP-1 drug?
Do not stop or restart any prescription on the basis of one study. If cost or side effects are making it hard to continue, tell your doctor, because there may be options. This is general information rather than medical advice.