When loss is gain

Over the course of his long career in medicine, V. Mohan has seen weight-loss drugs come and go. Some had a limited impact on weight loss; a few had severe side effects. However, the Chairperson of the Chennai-based Dr. Mohan's Diabetes Specialities Centre is suitably impressed by the new breed of drugs. In July 2024, the Central Drugs Standard Control Organisation approved Eli Lilly's tirzepatide, the active ingredient in its weight-loss drug Zepbound, for import and marketing in India. Mohan says tirzepatide shows a 15-20% weight loss, and Novo Nordisk's Ozempic leads to a 5-10% weight reduction in patients.

The link between diet and disease is straightforward in obesity: when calorie intake exceeds calories used, a person gains weight. Yet, the solutions are complex. Research has shown that reducing calories results in compensatory changes such as reduced metabolism, increased appetite and an imbalance in the hormones that affect appetite. Some hormones, secreted by the gut, impact how full a person feels. For example, the hormone ghrelin makes people feel hungry; its levels drop after they eat. Hormones such as peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and possibly glucose-dependent insulinotropic polypeptide (GIP) make a person feel full after a meal. These hormones stimulate the pancreas to release additional insulin when food is consumed orally, leading to better glucose control.

Drugs such as Ozempic are made of semaglutide, a synthetic variant of the GLP-1 hormone. Companies are developing synthetic GLP-1 and GIP analogues, called GLP-1 or GIP receptor agonists, that mimic the function of the hormones. Tirzepatide activates the receptors of GLP-1 and GIP, unlike semaglutides, which only act on GLP1-receptors. Mohan explains that GLP-1 works for a mere five minutes in the body. The synthetic versions are more effective in helping the body release insulin and last much longer.

But the drugs are not for everyone, Mohan cautions. When a person's body mass index (BMI) reaches 30, lifestyle changes alone often do not help, for the body tends to regain lost weight. For those with a BMI of 35 or higher, medications such as GLP-1 receptor agonists become more relevant. Unlike short-term treatments, these drugs are for long-term use.

While researchers globally recognise the benefits of GLP-1 drugs, the high cost and regulatory uncertainty are of significant concern in India. Anoop Misra, Chairman of Fortis C-DOC Hospital, New Delhi, says that some patients tell him they cannot afford to spend ₹10,000 a month on one drug. "We have no direction from Indian regulators on whether we can use these drugs as anti-obesity treatments," although off-label use continues based on FDA approvals.