New weight-loss drugs work, but require long-term use: Doctor

If you start taking the new weight-loss medications, be ready to stay with it for a long time, says Dr V Mohan, Chennai-based senior diabetologist who has worked extensively on the epidemiology and genetics of the disease. Excerpts from his chat with TOI, which is partnering with Novo Nordisk India to spearhead the ‘Choose Your Weight’ campaign, which aims to change the narrative around obesity.

Q: You have watched the evolution of weight-loss drugs through five decades of practice. Did you think they would emerge as such blockbuster drugs?

A: Efforts to develop effective weight-reduction medicines have been on for decades. In the late 80s and 90s, drugs such as sibutramine, phentermine and orlistat were introduced that facilitated modest weight loss of 1kg or 2kg, and rarely around 5kg. Some of these drugs had major side-effects and were eventually banned. We, as physicians, began to lose hope that any drug would come along that could offer significant weight loss without significant side-effects.


Then, we started getting drugs such as the GLP-1 receptor analogs (GLP-1RAs). Exenatide was the first; it came from the venom of a Gila monster in South America, and ensured significant weight loss than earlier drugs. Initially, we didn’t know how they worked, but they delayed gastric emptying and increased insulin release and glucagon reduction... They work through the potentiation of certain hormones in the intestine called GLP, the glucagon-like peptide. Researchers tried to make glucagon-like peptide itself, but it was very short-acting in the body. So, they started producing GLP-like substances.

Exenatide was followed by liraglutide. We found these mainly anti-diabetic drugs offered a two-in-one response by helping people reduce weight. Not everyone responded the same way; some had both weight reduction and HbA1c reduction, others had only one; a small percentage had neither.

Then came semaglutide, which took the world by storm. Semaglutide was a weekly injection marketed as Ozempic for diabetes and Wegovy for weight loss. It got approved in the US separately for weight loss and diabetes, marking the first time an anti-diabetic drug was used solely for weight loss. It became a blockbuster drug with billions in sales, and millions started using it due to its unprecedented weight loss results, often 10-15 kg. The drug became so popular that it was hard to find, and new factories had to be built to meet the demand. Celebrities started using it, and before-and-after pictures were circulated widely. They were sold on the black market. This kind of success story with any drug had never been seen in the history of medicine.

Q: But there are concerns about their side-effects…

A: These drugs, including liraglutide and exenatide, work on the stomach, causing nausea initially. They must be started at a small dose and gradually increased to minimise side-effects. After four to eight weeks, side-effects such as nausea, vomiting, or diarrhoea usually settle.

Stomach paralysis is a rare side-effect. Another rare but serious side effect is blindness due to anterior ischemic optic neuropathy. One in 7,000-10,000 people who take these drugs can go blind. Such rare side-effects will surface only when millions start taking a drug. It’s like the Covid vaccination: as mass vaccination was carried out, we saw side-effects. We don’t know why those idiosyncratic reactions occur, but we must remember there’s no big FDA warning so far. Clearly, its benefits far outweigh the risks.

Q: The experience in the West has shown that almost 50% of the patients stop the drug after a year or so. Why does this happen?

A: Cost is a disadvantage, especially since there are no generic versions. The other reason is “plateauing”. After a patient loses 10kg, 15kg or 20kg, the drug’s effect plateaus off. In trials, those who stopped taking the drug started gaining weight. In one year, they regained 50% of the weight they lost. In practice, the minute people’s weight starts plateauing after taking the drug for a year or so, they stop as they don’t want to spend money on a drug that has seemingly stopped working.

People think diet and exercise will help them, but obesity is complex. It’s not just calories in, calories out. If that was the case, there would be no need for these drugs. All these years people have been trying to lose weight but failed because of the brain: when one starts losing weight, the brain realises that you lost weight and immediately corrects itself trying to regain your weight. The point is that one needs to continue taking the drug to stay on that plateau.

Q: New weight-loss drugs came to India only recently. What can we expect next?

A: In India, we were waiting for semaglutide and tirzepatide to become available. The injectable forms were delayed until recently, but by March 2026, the patent for semaglutide will expire, allowing generic versions to enter the market. There are over 20 companies that plan to make generic versions available.

Companies are now developing a third drug, retatrutide, which targets three hormones: GLP, GIP, and glucagon. It’s in late stages of development and shows promise for even greater weight loss.

These drugs offer numerous benefits beyond weight loss, including reduced risk of heart attack, improved kidney function, and potential cognitive benefits. They also help reduce snacking and other addictions, like smoking. One of my patients who was asked to undergo bilateral knee replacement decided to go on weight-loss medication first; he lost 20kg and didn’t need replacement as the knee pain vanished.

Q: What are the points to consider before taking up weight-loss drugs?

A: One has to consider that when one loses 10kg, it’s not 10kg of fat. It’s 7kg of fat and 3kg of muscle. That means from the little muscle you have, 3kg is going to go. Hence, people get ozempic facies with muscles gone… As your strength will be reduced, one needs to increase protein intake, do some weight training and muscle strength training.


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