For 65-year-old Ramesh Kumar, walking had become impossible — just 50 steps could make him breathless. The newer weight-loss drugs came to his rescue. After losing 25 kgs, he can now walk 4 km without feeling stressed. Such improvements in fitness and mobility may be enough for a person to maintain their weight without the need for more medications.But can stopping the GLP-1 medicine put you at greater risk of heart attacks, strokes, or deaths? A recent study that analysed the data of 80,000 people seems to suggest so. While many may continue to need the medicines long-term — and the decision to stop or reduce dosage should not be taken without consultation — doctors say that these results should not scare people already taking them. “Remember, the goal is not just to lose weight, but to maintain that weight loss and protect your metabolic health in the long run…Do not start these medicines casually or stop them without consulting your doctor. Weight management is not a 100-metre sprint; it is a marathon. These medicines can be highly effective, but they require medical supervision and a long-term commitment,” said Dr Anoop Misra, chairperson, Fortis C-Doc.What did the study show?The results are based on the analysis of health data from 80,302 people with diabetes who started taking GLP-1, with 60.5% of the participants discontinuing the treatment mostly after a year. Among those who stopped taking the medicine, the risk of cardiovascular diseases went up two-fold, according to the study.“In people with T2D and without previous cardiovascular disease, interrupting a therapy with GLP-1RA was associated with a higher risk of a composite of myocardial infarction (heart attack), stroke, or death from any cause compared to those continuing the treatment,” the study concluded.Yet, experts say it is not a final word on how and when to stop taking the medicines. Dr Ambrish Mithal, Chairman, Endocrinology and Diabetes, Max Healthcare, has two important caveats to the study. “One, it has looked at outcomes in patients who have been using GLP-1 drugs 2004 onwards, which means most of them were not on the newer therapies. In fact, just over 8,000 people, or 14.3% of the participants, were on semaglutide and none were on tirzepatide. Two, it does not have data on the baseline risk of the participants. So, we do not know whether their risk of cardiovascular diseases such as heart attack and stroke reduced with the medicines and then went up to a level more than it was, went up to the same level as it was, or went up but remained lower than before.”The study admits: “…given our study design, we could not determine the relative risk of starting and interrupting a GLP-1RA compared with never using such medications. While the findings are not final and conclusive, it gives us an important indication. We now know that the GLP-1 drugs offer some protection against cardiovascular diseases which seem to go away when the drugs are discontinued.”What are the contentions that doctors have?Dr Yashendra Sethi, a physician-researcher and founder of Nexoria Institute of Cardiometabolic Excellence (NICE)-Dehradun, said, “We have recently written to the journal about this study because there are certain anomalies that we have noticed.”Story continues below this adHe goes on to explain that studies on GLP-1 drugs have demonstrated around 12% reduction in the risk of cardiovascular disease. “So, the risk increasing two-fold does not make sense. If a medicine is stopped, the loss of benefit has to be equal to the benefit that a person got, it cannot be more than that.”The study also shows that the weight gain in the participants was limited, which does not explain the drastic change in their cardiovascular risk. Also, a high proportion of the adverse outcome was death (which may or may not be associated with a cardiovascular disease). “There is a possibility that many of the patients discontinued their treatment because of other conditions,” explained Dr Sethi.There is a need for more studies to determine what happens when the therapy is stopped — and whether it should be stopped at all, the experts said.Why do people discontinue GLP-1 therapies?Dr Misra has seen around 15–25% of patients stopping treatment over time. The common reasons are side effects such as nausea or stomach discomfort, lower weight loss than expected or simply quitting after achieving satisfactory weight loss. In a smaller number of patients, the high cost of long-term treatment is a factor. “Overall, acceptance of these medicines has improved over time.”Story continues below this adFor Dr Mithal, the finding that is more important — and perhaps a little disheartening — is that around 60% of the patients discontinued the therapy. “Most people are very enthusiastic initially but once they have lost a significant amount of weight, they do not even ask their doctors before stopping the treatment. This is despite all the counselling and advice that we give.”He cites several reasons, the biggest being pressure from family and friends. “Most users with weight loss as the only goal discontinue after initial targets are met following family members’ fear about GLP1 RAs being new drugs and their side effects. For some patients the side effects such as gastritis and nausea do become bothersome. Others want to do away with their inability to enjoy foods. When they start putting on the weight again, they come back and say that they had actually stopped taking the medicine,” Dr Mithal said.What happens when you stop?Most people are likely to regain the weight and lose the protection offered by the medicine. “Weight regain is common after stopping these medicines, although the extent varies from person to person. Some patients regain a substantial part of the weight they have lost, while others maintain their weight through careful eating and regular exercise. People with diabetes may also experience a rise in blood sugar levels,” said Dr Misra.While the effect of stopping the medicine is now known, Dr Mithal says the effects of stopping and then restarting the treatment again is not yet known — could it make a person drug-resistant, could the drug be more effective? Researchers and doctors across the world are currently looking for answers to these questions, he said.Story continues below this adSo, what is the current approach?The doctors have mostly taken to lowering the dose to maintain the weight. “For anyone with diabetes or other co-morbidities, we continue with the medicine — after all they would continue any other therapy life- long. For patients taking the drug mainly for weight loss, we taper the dose to the lowest at which they are able to maintain the weight. This does not work for some as they might start putting on weight even when we reduce it slightly,” said Dr Mithal.Dr Misra emphasises the need for diet, protein intake and physical activity as non-negotiables. “Regular exercise, including strength training, becomes especially important. In fact, substantial weight loss often makes exercise easier,” he added.