With the launch of Wegovy by Danish pharmaceutical giant Novo Nordisk and US major Eli Lilly’s Mounjaro already in circulation, Indians now have two injectable therapies for obesity management. Both therapies can be effective for weight loss, with users losing 15 per cent to 20 per cent of their body weight, almost equivalent to bariatric surgeries.

This is significant considering obesity is on the rise in India, with nearly 254 million people living with it, according to the INDIAB study. We spoke to Dr Ambrish Mithal, chairman, endocrinology, Max Healthcare.

The GLP-1 receptor agonists mimic natural gut hormones responsible for blood sugar and appetite control, such as semaglutide – the active ingredient in Wegovy. It improves secretion of insulin, inhibits glucose production in the liver and slows down digestion. Tirzepatide, sold as Mounjaro, additionally mimics the GIP hormone, primarily by stimulating insulin release from the pancreas. GIP also influences lipid metabolism and cardiovascular function.

Other than weight loss, both have cascading benefits on other health conditions like cardiovascular diseases, kidney disease, non-alcoholic fatty liver disease and obstructive sleep apnoea. While the popularity of this class of medicines soared in 2017 after diabetics on semaglutide started losing weight — leading to the off label use of the medicine by many for weight-loss — predecessors of this medicine have been available in the market for years, showing a good safety profile.

“The data from various GLP-1 RA trials are applicable to Indians as well because global trials did have Indian participants. Besides, other GLP-1 RA drugs have been in use since 2005, with a good safety profile. Over the years, the capacity for weight loss has increased,” says Dr Mithal. “It will be beneficial for Indians because of the way we tend to store fat around the abdomen, even with low BMI (body mass index), or what we call skinny fat,” he adds.

Indians already have a poor muscle mass, so would they want to lose more of it? “The muscle loss with these medicines is equivalent to that seen with any sharp weight reduction, be it through diet or bariatric surgery. There is no evidence to show that the muscle loss with these medicines is more. In fact, there is data emerging that these drugs and some of the newer ones may be muscle-protective,” says Dr Mithal.

But there’s a caveat. The drugs have to be taken in conjunction with a good diet and exercise to ensure healthy weight loss.

There are certain contraindications. The drugs are known to initially cause gastrointestinal side effects such as nausea and vomiting.

“So, people who are at a high risk of gastric conditions should not be given the medicine. It should not be prescribed in people who have long standing diabetes with sluggish peristalsis (contraction and relaxation of the digestive track to push the food through), gastric obstructions and those prone to nausea. In rare cases, the drug is known to cause stomach paralysis. It should not be prescribed to people who have a family history of thyroid cancers as well,” says Dr Mithal.

Trials with semaglutide have shown the ability to reduce the risk of major cardiovascular events, such as heart attacks and strokes, by 20 pr cent and the risk of all-cause mortality by 19 per cent. Studies have shown a 69 per cent reduction in heart failure events. The drug can resolve fatty build-up in the liver in 63 per cent of patients and improve liver fibrosis — the hardening of liver tissue due to fatty deposits — in 37 per cent of cases.

Tirzepatide, while reducing body weight by 20 per cent, has been approved for the treatment of obesity-related obstructive sleep apnoea — a condition where a person’s breathing stops and starts while they sleep. Trials have also shown that it can improve lipid profile. And, the reduction in the risk of cardiovascular death and all-cause death by 20%.

“There is no doubt that the medicines are effective for kidney and heart conditions. There is also evidence that has emerged about fatty liver disease. But what I am most excited about is the evidence to show that the medicines are associated with lower risk of Alzheimer’s and other dementia,” says Dr Mithal.

He noted how those who have used these drugs for some time have reduced cravings now.  “They are not only eating smaller but healthier meals. There is also evidence to show that it helps with alcohol addiction,” he says.

The drug is approved for use in children and adolescents in other countries to combat teen obesity. There is a small subset of adolescents who may indeed benefit from these drugs — someone who is obese and has other associated problems such as diabetes, polycystic ovary, or facial hair for women, or those who are unable to shed the weight despite lifestyle interventions.

However, Dr Mithal advises caution. “If you reduce nutritional intake in children, it may have negative consequences. Also, how long it can be given?” he asks.

Dr Mithal says it can be beneficial for relieving symptoms of conditions such like PCOS (polycystic ovary syndrome) in women, improving their chances of pregnancy. However, the drug has to be discontinued during pregnancy. “A lot of answers are needed,” he says.

There might be a case for tapering the doses of the medicine in some patients, although there is no data yet for this. In fact, Dr Mithal says, there are studies to show that those who discontinued the medicine started putting on some of the body weight back. “The tapering of the drug has to come with change in lifestyle to sustain the weight loss,” he adds.