Weighing in on weight-loss drugs

INDIA’s obesity numbers are rising rapidly. A recent Lancet study projected that 449 million Indians (218 million men and 231 million women), nearly one-third of the country’s population, will be obese by 2050. In 2021, the number of Indians either overweight or obese stood at 180 million.

As India’s diabetes and obesity numbers grow at an alarming rate, this offers a big opportunity for weight-loss drugmakers, and most of the international pharma companies are actively working to tap this burgeoning market. In the past four months, two major firms have launched their injectable weight-loss drugs in India.

In March this year, US drugmaker Eli Lilly & Co was the first to launch its anti-obesity drug, Mounjaro, in India. The injectable drug, used to treat obesity and type-2 diabetes, is to be taken once a week. Last week, Danish pharma firm Novo Nordisk launched its anti-obesity injectable drug, Wegovy.

Most weight-loss drugs work by helping the body effectively manage blood sugar, making a person feel less hungry and slowing digestion, so the person feels full longer. These drugs mimic the action of a hormone called glucagon-like peptide-1 (GLP-1), which helps the body regulate its appetite.

“Their basic mechanism is not new as similar agents from earlier generations have been in use for over two decades,” says Dr Anoop Misra, chairman, Fortis C-DOC Hospital for Diabetes and Allied Sciences, New Delhi.

“We have been using these GLP-1 drugs routinely for our diabetes patients. While the drugs also help in weight loss, these never really caught on because the weight loss induced was not much, say between 3 kg and 5 kg. But these were and are very good for controlling diabetes,” says Dr Ambrish Mithal, chairman and head of endocrinology and diabetes at Max Healthcare (Pan Max), New Delhi.

But what sets the newer drugs apart is their enhanced efficacy for weight loss and organ protection. These should be primarily considered for individuals with severe obesity, those unable to lose weight despite lifestyle modifications, or patients with physical limitations such as osteoarthritis of the knees, points out Dr Misra, who is also the director of the National Diabetes Obesity and Cholesterol Foundation.

“Some of these medications have the potential to cause weight loss up to 22 per cent of the body weight, which in previous years was only achievable through surgery,” says Dr Sachin Mittal, consultant, endocrinology, Fortis, Mohali.

For the obese struggling to lose weight, particularly those who are not able to exercise because of it, these new drugs (Wegovy/semaglutide and Mounjaro/tirzepatide) are going to be life-changing literally, feel most endocrinologists.

“An obese person weighing more than 100 kg may not be able to exercise properly, or at all. However, with the help of these drugs, if he/she achieves even 18 to 20 per cent weight loss, his parameters are bound to improve,” says Dr Mithal, who was awarded the Padma Bhushan (2015) for his contribution in the field of endocrinology.

“The patient will be more energetic, his diabetes medicine may be reduced, his BP might go away, his fatty liver might reduce drastically. And this weight loss is not just a physical win, it usually motivates patients to continue or stick to their lifestyle modifications. It’s a win-win situation for both the patient as well as the doctor,” he adds.

Dr Mittal agrees: “A 20 per cent weight reduction is a game-changer for the obese. Patients are able do more physical activity. There is less pressure on joints, breathlessness reduces, and the exercise capacity also improves.” However, when weight loss happens through whatever means, both fat mass and muscle mass are lost. The amount of fat loss is proportionally more. A protein-rich and balanced diet and resistance/strength training on a regular basis can keep the muscle loss in check, stresses Dr Mittal.

“Primarily, these drugs may be used to induce weight loss, but their overall benefits in the long run are much more. Many diabetes patients, especially obese ones, have been able to stop their insulin injections and sometimes even oral medications,” says Dr Mittal. Their diabetes has gone into remission. He recalls a young obese patient from Nabha, whose type 2 diabetes went into remission after he was put on weight-loss drugs. “At 18, he was taking four insulin injections daily. He was able to reduce a significant amount of weight after being on oral weight-loss medication for two years. Now his diabetes is in remission. He is off insulin injections and does not even need any oral medication for diabetes, but he maintains a strict diet and exercise routine.”

If oral medications with 5 to 10 per cent weight-loss capacity could achieve such results, the potential benefits of these new injectable drugs should be much more.

According to treatment protocols at the moment, these drugs need to be used for a longer duration. But a significant number of patients may have to take these drugs lifelong just like insulin, says Dr Mithal. “For younger patients, we would like to use it for shorter periods as part of the overall treatment regimen,” he adds.

That’s because after stopping treatment, if diet and exercise are not continued, chances of the weight coming back are quite high, warns Dr Misra.

The red flags

In a society obsessed with appearance, most experts are, however, concerned over the misuse of these drugs and suggest stringent regulations regarding their availability, and ensuring their use only under strict medical guidance, as these drugs, like any other drug, too have side-effects.

Gut-related side-effects are common and include nausea, vomiting, diarrhoea, constipation. “But these effects are mild and manageable in most patients and recede in few weeks,” says Dr Mithal.

There are also some serious though less common side-effects like pancreatitis and thyroid tumours. Individuals having a history of pancreatitis, medullary thyroid cancer, or significant gastrointestinal disorders should not be prescribed these drugs, says Dr Misra.

“Some serious side-effects have been found to be theoretically possible, including an increased risk of certain eye conditions like diabetic retinopathy and age-related macular degeneration. However, these are not yet proven, but studies are on, and those having a family history of these medical issues should not be prescribed these medicines,” adds Dr Mithal.

At the moment, the cost factor for most of these weight-loss drugs, whether oral or injectable, is quite high — ranging between Rs 12,000 and Rs 17,000 a month, making it out of reach for millions of Indian patients. But with semaglutide’s patent expiring in 2026, several Indian pharmaceutical companies are ready to launch their own low-cost versions next year.

Experts believe the global market for GLP-1 drugs like semaglutide could cross $100 billion by 2030. With obesity and diabetes on the rise across the world, cheaper generic versions could make a big difference.

Major pharma companies, including Dr Reddy’s, Sun Pharma, Cipla, Lupin, Biocon, Zydus Lifesciences and Aurobindo Pharma, are likely to introduce generic versions of these drugs which may cost as little as Rs 500 a month, making weight-loss and diabetes treatment more affordable to millions not just in India, but around the world.

But, keep in mind, do not take the drugs without the guidance of a doctor.

Don’t self-medicate

These drugs should be taken only on the advice of a doctor. There have been many instances where people have taken such weight-loss drugs without any supervision. Many of them have landed in hospital with severe gastro symptoms.

— Dr Sachin Mittal, Fortis, Mohali

Figuring it out

— Wegovy (semaglutide) is prescribed for weight loss and to lower cardiovascular risks in adults with a body mass index (BMI) of 30 or higher, or adults with a BMI of 27 or higher who also have a weight-related health condition such as diabetes, high cholesterol, high blood pressure.

— Mounjaro (tirzepatide) is approved for type 2 diabetes, and doctors may prescribe it off-label for weight loss.

— Clinical trials have shown that Wegovy, combined with diet and exercise, can cause up to 20 per cent body weight reduction in 1 out of 3 persons within about 68 weeks.

— There is 20 per cent lower risk of major cardiovascular problems such as stroke, heart attack, and death due to cardiovascular disease, especially in people who already have a heart condition and are obese.