Stopping GLP-1 drugs was linked to higher cardiovascular risk, including heart attack, stroke and death, in people with type 2 diabetes.
Interrupting or stopping treatment for as little as six months was associated with increased risk compared with remaining on the medication.
After two years without GLP-1 therapy, the risk of major cardiovascular events was up to 22 per cent higher than among people who continued treatment.
Senior author Ziyad Al-Aly, a clinical epidemiologist at Washington University School of Medicine and chief of the Research and Development Service at the VA Saint Louis Health Care System, said: “There is enormous exuberance about starting GLP-1 drugs, but not nearly enough attention to what happens when people stop.
“Many quit after a few months because of cost, side effects or shortages.
“When they stop, it’s not just weight that comes back; they experience a resurgence in inflammation, blood pressure, and cholesterol. Weight regain is visible; the metabolic reversal is not.
“Our data suggest this metabolic whiplash is detrimental to heart health.
“Restarting the medication helped restore some protection, but only partially, showing that discontinuation leaves a lasting scar.”
Researchers at Washington University School of Medicine in St. Louis analysed data from 333,687 US veterans with type 2 diabetes who were followed for up to three years.
The study examined major adverse cardiovascular events, including heart attack, stroke and death.
Of the participants, 132,551 had been prescribed GLP-1 drugs and 201,136 had been prescribed sulfonylureas, another class of diabetes medication.
GLP-1 medicines included the semaglutide drugs Ozempic and Wegovy and the tirzepatide drugs Mounjaro and Zepbound.
Treatment status was reassessed every six months. During the study, 26 per cent of GLP-1 users stopped taking the medication completely, while about 23 per cent had a treatment gap of at least six months before restarting.
People who remained on GLP-1 treatment continuously for three years had an 18 per cent lower risk of major cardiovascular events than those taking sulfonylureas.
This amounted to around four fewer major cardiovascular events for every 100 people over three years.
Participants who remained on GLP-1 therapy for two years before stopping had a seven per cent lower risk, while those who continued for two-and-a-half years before discontinuing had a 15 per cent lower risk.
People who discontinued treatment before 18 months showed no significant reduction in cardiovascular risk compared with participants taking sulfonylureas by the end of the study.
Treatment interruptions were also associated with weaker cardiovascular benefits.
People who used GLP-1 drugs continuously for three years had an 18 per cent reduction in risk, compared with an average 12 per cent reduction among those who temporarily stopped treatment and later restarted.
Even a six-month interruption before restarting was associated with a four to eight per cent increase in cardiovascular risk compared with continuous use.
People who stopped GLP-1 therapy for one year without restarting had a 14 per cent higher risk of cardiovascular events compared with continuous users. After two years without treatment, the increase reached 22 per cent.
Al-Aly said: “Clinicians should treat adherence to GLP-1 treatment as an important outcome in its own right — not an afterthought.
“Health systems need plans in place to help people continue their medication indefinitely, recognising that GLP-1s treat chronic conditions.
“That includes proactive management of side effects, candid conversations about the long-term nature of treatment, infrastructure to identify and support patients at risk of stopping and addressing the cost barriers that make GLP-1 therapy unsustainable for many.”
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