Weight Loss Drugs Not Enough, Lifestyle Changes Needed, Say Experts

Hyderabad: A Class 9 student from West Bengal, has been struggling with obesity for six years. His attempts at weight loss included bouts of exercise and dietary restrictions, but with little success. What proved effective was a new weight-loss drug that helped him shed 14 kg in just three months.

“I got serious about my weight only this year. I had initially tried semaglutide, but it did not work for me. Then my doctor recommended tirzepatide, and I have seen amazing results. From 106 kg, I have reduced to 92 kg now in just three months,” the student said.

Weight-loss medications, particularly glucagon-like peptide-1 (GLP-1) receptor agonists, have recently emerged as game-changers in obesity management. Drugs such as liraglutide, semaglutide, and tirzepatide have shown impressive outcomes, offering hope to those unable to achieve results through traditional approaches. But experts caution that the benefits come with caveats — cost, side effects, and the risk of regaining weight once treatment stops.

GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) are natural gut hormones that regulate blood sugar and appetite. GLP-1 receptor agonists mimic these hormones by binding to receptors in the body, producing weight-loss and metabolic benefits.

Approved options include liraglutide, dulaglutide, semaglutide, and tirzepatide. Retatrutide, a triple agonist now in Phase 3 trials, targets GLP-1, GIP, and glucagon receptors and shows even greater promise than tirzepatide (dual agonist) or semaglutide (single agonist).

In India, semaglutide, tirzepatide, liraglutide, and dulaglutide are available under specific brand names.

According to Dr Rakesh Kalapala, director of endoscopy, Centre of Obesity, AIG Hospitals, GLP-1 receptor agonists are among the most effective drugs available. “Liraglutide leads to an average weight loss of 5 to 8 per cent, translating to about 5 to 8 kg depending on duration. Semaglutide produces greater efficacy, averaging 12-16 per cent body-weight loss, or roughly 12-17 kg in trial settings. The newer tirzepatide, which also targets GIP receptors, has shown weight loss up to 18 per cent,” he said.

The drugs act through multiple mechanisms: stimulating insulin release, suppressing glucagon secretion, slowing gastric emptying, and regulating appetite by acting on the brain’s satiety centres. Together, these effects reduce cravings, enhance fullness, and lower overall food intake.

Dr Kalapala emphasised that GLP-1 receptor agonists not only reduce weight but also improve broader health outcomes. “They lower BMI, waist circumference, and blood sugar levels while offering cardiovascular benefits. Importantly, they also reduce the risk of progression to type 2 diabetes in high-risk individuals. The weight loss is more pronounced when these drugs are combined with lifestyle interventions like exercise and dietary modifications,” he said.

For patients, the journey is not always straightforward. A 32-year-old social science researcher from Hyderabad, who recently started tirzepatide, shared her experience.

“I have struggled with weight issues since adolescence. Earlier this year, I had to choose between bariatric surgery and GLP-1 therapy. I didn’t have the luxury of time for surgery recovery, so I opted for the injection. I tried gymming but instead of losing weight, I gained back double. My cortisol was high, my health reports poor, and I couldn’t follow heavy workouts. After starting tirzepatide, the stubborn weight finally started shedding. It’s not magic, though. The body takes time to adjust. I had nausea and loose motions, which made me weak, but eventually I felt lighter and regained control over my body and mind,” she said.

Dr Rohini Kasturi, consultant endocrinologist, said that the drugs were recommended only for patients who are obese or overweight with comorbidities. “They are prescribed for adults with a BMI of 30 or above, or those with a BMI of 27 and weight-related conditions such as hypertension, diabetes, dyslipidaemia, or sleep apnoea. For Asians, the BMI cut-offs are lower than in the West: BMI 23–24.9 is considered overweight, while obesity begins at 25,” she explained.

Both experts agree that while the benefits are significant, there are downsides. Gastrointestinal issues such as nausea, vomiting, diarrhoea, and constipation are the most common side effects, typically early and dose-related. Rare but serious risks include kidney injury, pancreatitis, gallbladder problems, or worsening eye conditions from rapid sugar control. The drugs should be avoided by individuals with a personal or family history of certain thyroid cancers or MEN2, a genetic condition affecting hormone glands.

Cost remains another major barrier. “These injections can cost anywhere from Rs 14,000 to Rs 27,000 per month, depending on dosage, making them inaccessible to many patients,” Dr Kasturi said.

Perhaps the biggest limitation is what happens when treatment stops. “Weight regain is almost inevitable once GLP-1 therapy is discontinued. Studies show patients regain about two-thirds of the weight lost within a year, despite lifestyle changes,” Dr Kalapala explained. After 68 weeks of semaglutide treatment, patients lost an average of 17.3 per cent of body weight, but regained about 11.6 percentage points within a year of stopping. Tirzepatide shows similar trends, with around 14 per cent regain after discontinuation.

This rebound stems from biological adaptations: once the drug’s effects are removed, appetite returns, energy expenditure drops, and hormonal shifts promote renewed weight gain. Experts say strategies such as tapering doses, maintaining high levels of physical activity (about 250 minutes per week), and strict lifestyle modifications may slow this process. But they also stress that obesity is a chronic condition, often requiring long-term or lifelong solutions.

1. Anti-obesity drugs mimic gut hormones (GLP-1, GIP) to increase insulin, suppress glucagon.

2. They slow down stomach emptying, reduce cravings and boost satiety.

3. They could better blood sugar control, lower BMI and waist size, reduce risk of type 2 diabetes, cardiovascular protection

4. Common side effects include nausea, vomiting, diarrhoea, constipation

5. Weight regain likely after stopping as patients could regain two-thirds of lost weight within a year.

6. Experts suggest patients combine diet control and exercise for better results.