Weight loss medicines work by suppressing appetite, increasing satiety and altering gut–brain signalling.
Over the past two years, India has witnessed a quiet revolution in obesity management. For the first time, highly effective weight loss medicines have become available widely. Drugs such as semaglutide and, more recently, tirzepatide have helped many people lose 15–20% of their body weight — results that were previously achievable only with bariatric surgery.
But as enthusiasm rises, an uncomfortable question is beginning to surface: what happens when these medicines are stopped? To understand the issue, we must first recognise that obesity is not simply a matter of willpower. It is a chronic, relapsing disease driven by complex interactions between biology, behaviour, and environment. People often struggle with this condition throughout their life. When people lose weight by any method (diet, exercise, drugs, bariatric surgery), the body responds with powerful counter-regulatory mechanisms: hunger hormones rise, satiety hormones fall, and energy expenditure decreases. In simple terms, the body “fights back” to regain lost weight.
A large and rigorous systematic review and meta-analysis of all weight loss drugs, recently published in the British Medical Journal, has provided the clearest answer so far. Researchers analysed data from 37 studies involving more than 9,000 adults who had used weight loss medicines and were then followed after stopping treatment.
The findings temper the initial optimism. On average, people regained weight at a rate of about 0.4 kg per month after stopping weight loss medication. For the newer and more powerful drugs — semaglutide and tirzepatide — the rate of regain was even faster, close to 0.8 kg per month. Based on these trajectories, body weight returned to baseline in about 1.7 years of stopping treatment. More importantly, along with weight, metabolic health deteriorated. Improvements seen during treatment — lower blood sugar, better cholesterol levels, and reduced blood pressure — gradually disappeared. Most cardiometabolic benefits were projected to return to pre-treatment levels within about one to one-and-a-half years after discontinuation.
An important and perhaps surprising finding was that weight regain after stopping medicines was faster than after stopping structured lifestyle programmes based on diet and physical activity. This does not mean that lifestyle approaches are superior in producing large weight loss, but it does highlight a key difference: behavioural changes, when sustained, may leave behind habits that partially protect against rapid regain. Medicines, on the other hand, primarily act while they are being taken.
Our expectations need rethinking. For people with severe obesity, diabetes, fatty liver disease, or cardiovascular risk, they can be life-changing. Obesity, like hypertension or diabetes, often requires long-term treatment. Just as blood pressure rises when antihypertensive drugs are stopped, weight tends to return when anti-obesity drugs are withdrawn.
Given the high cost of these medicines and concerns about long-term affordability, we need pragmatic strategies to minimise weight regain. For some patients, long-term use at the lowest effective dose may be necessary. Rather than abrupt discontinuation, gradual dose tapering might help slow rebound weight gain, although robust data on this approach are still limited. At this time, diet and exercise efforts should be increased majorly. An emerging idea is intermittent use, periods of treatment interspersed with drug-free intervals, combined with close monitoring. This approach may reduce costs and side effects, though it needs formal evaluation. There could be a step-down to milder medications. After substantial weight loss with potent agents, some patients may be maintained on older, less expensive, or milder weight loss drugs to blunt rebound gain.
The period of successful weight loss offers a critical window of opportunity. Physical activity should be actively escalated after weight reduction, not before. Exercise is far easier and more sustainable at a lower body weight and can help defend against regain. Structured dietary approaches, including partial meal replacement plans, higher protein intake and strict control of ultra-processed foods, may help stabilise weight during and after drug withdrawal. This also needs more research.
Weight regain should not be seen as a lack of discipline or effort. It reflects the body’s biological response to weight loss, not personal failure. For policymakers and clinicians, the challenge is to integrate these drugs into a long-term, comprehensive obesity care model, rather than viewing them as short courses of therapy. Cost-effective strategies, prioritisation of high-risk patients and strong lifestyle support systems will be crucial, particularly in a country like India.
(Dr Misra is Executive Chairman, Fortis CDOC Hospital for Diabetes and Allied Sciences, New Delhi)
Curated by Shiv Shakti Mishra
