Obesity: Are GLP-1 pills sustainable?

Obesity was recognised as a disease by the World Health Organisation in 1948. It is a chronic, complex condition marked by excess fat accumulation and drives non-communicable diseases such as type 2 diabetes, cardiovascular disease, joint disorders, and certain cancers. It is also associated with cognitive decline, dementia, and premature death.

India, home to nearly 20 per cent of the world’s population, has seen major dietary and lifestyle changes over the past two decades, leading to a sharp rise in non-communicable diseases. For Indians, a body mass index (BMI) above 23 kg/m² is classified as overweight, as obesity-related complications occur at lower BMI thresholds than in Western populations. The ICMR–INDIAB study estimated in 2021 that 254 million Indians had generalised obesity and 351 million had abdominal obesity, with costs projected to reach 2.47 per cent of India’s GDP by 2060.

Obesity cannot be managed through a single intervention. Weight gain occurs when energy intake surpasses expenditure. Clinicians recommend reduced energy intake, dietary modifications, and increased physical activity, but responses vary, and weight regain after successful loss is common due to compensatory mechanisms. Bariatric surgery and GLP-1 agonists assist in weight loss. Bariatric surgery remains the most effective option for significant, sustained weight loss, although cost and invasiveness limit adoption. In experienced hands, endoscopic bariatric surgery is safe, with risks comparable to gallbladder surgery.

Medical management  

Glucagon-like peptide 1 (GLP-1) is a gut hormone that promotes satiety, regulates blood glucose and slows gastric emptying. It stimulates insulin secretion, suppresses glucagon and reduces appetite. 

GLP-1 receptor agonists have been used to treat type 2 diabetes since 2005. Their role in obesity began in 2014 with liraglutide, followed by semaglutide, marketed as Wegovy. The dual GLP-1 GIP agonist tirzepatide is marketed as Mounjaro; both Wegovy and Mounjaro are weekly injections. 

These drugs are more effective than diet and exercise alone, producing weight loss of about 15  per cent with Wegovy and 20 to 25 per cent with Mounjaro. Many patients discontinue treatment within a year due to high costs, limited availability, achieving of target weight, or side effects. Gastro-intestinal effects, including nausea, vomiting, and diarrhoea, may necessitate a dose reduction or discontinuation of therapy. Rarely, pancreatitis can occur, presenting as severe abdominal pain that requires urgent attention.

Commenting on their use in India, Dr V Mohan, chairman of a diabetes specialities centre, said, “GLP-1-based medications are increasingly used in India. Injectable semaglutide (Wegovy and Ozempic) was introduced last year, and tirzepatide (Mounjaro) has been available for almost a year. Due to high out-of-pocket costs, uptake remains limited, though these products are already a major success. However, many patients are reluctant to take them long term, and weight gain recurs after discontinuation.” 

The fallout of discontinuation 

A study by academics at the University of Oxford, published in the British Medical Journal, reviewed 37 weight loss drug trials involving 9,341 participants. Mean treatment duration was 39 weeks, with 32 weeks of follow-up. 

Senior author Dimitrios Koutoukidis reported that those who stopped medication regained weight at a rate of 0.4 kg per month, returning to baseline within 1.7 years. Cardiometabolic markers, including HbA1c, fasting glucose, cholesterol, triglycerides, and systolic and diastolic blood pressure, also returned to baseline within 1.4 years. Weight regain was faster than after behavioural programmes alone. 

Muscle mass and bone density loss

Dr Pranav Kumar, a diabetes and weight-loss physician at Royal Wolverhampton NHS Trust and a member of the World Obesity Federation, has used GLP-1 agonists since 2009. He notes patients lose mainly fat but also have small reductions in muscle mass and bone density.  The SURMOUNT 1 DXA sub-study last year showed that weight loss comprised 25 per cent muscle and 75 per cent fat; however, case reports in older, inactive individuals have reported higher percentages of muscle mass loss. Dr Kumar further opines that two years of injections cost about as much as bariatric surgery, which has stronger evidence for sustained weight loss, longevity and complication prevention. Newer drugs are in the pipeline with tablet alternatives of these drugs in place of injection, but the amount of weight loss with tablets is much lower, and they are better used for diabetes alone.

Dr V Mohan states that treatment should only commence when patients are prepared for long-term use, as rebound weight gain is undesirable. If the cost of injectable treatment is prohibitive and BMI exceeds 40, or if the risk of complications is high, bariatric surgery should be considered, advises Dr Kumar.

It is not uncommon for people with type 2 diabetes to stop medication after gastric bypass surgery. Both experts stress that obesity is a chronic condition, and management should prioritise sustained weight loss rather than short-term injections. Improving access to treatment would allow more people with obesity to benefit and should be combined with strong prevention efforts.

How to lose weight

•Indian diets have high intake of low-quality carbohydrates (white rice, milled whole grains and added sugar), high levels of saturated fat and low protein intake. Reduce the overall amount of calories, primarily of sweets, cakes, and biscuits. Replace some carbohydrates with protein from plants, dairy, eggs or fish

•Thirty minutes brisk walk five times a week or 75 minutes twice a week.

•GLP-1 receptor agonists can be used when diet and exercise are insufficient to reduce weight or when there is marked obesity.

•GLP-1 receptor agonists and dual GLP-GIP agonists have multiple benefits; weight loss surgery is a cost-effective option for those who are eligible. 

Quick facts

•Obesity is a chronic condition, and management should prioritise sustained weight loss rather than short-term injections.

•Many patients on GLP-1-based medications discontinue treatment within a year due to high costs, limited availability, achieving of target weight, or side effects.  

•A study by academics at the University of Oxford, published in the British Medical Journal, reviewed 37 weight loss drug trials involving 9,341 participants. The author of the study reported that those who stopped medication regained weight at a rate of 0.4 kg per month, returning to baseline within 1.7 years.

(The author is a consultant haemato-oncologist with a special interest in stem cell transplantation at Royal Wolverhampton NHS Trust, UK. He can be reached at [e-mail].)