Retatrutide for weight loss: Expert explains its benefits, side effects and availability in India

New Delhi: Retatrutide, a weight-loss drug still under clinical investigation, has drawn attention for its encouraging clinical trial results. What makes it different is that it targets three hormone receptors involved in appetite and metabolism, rather than one or two. Unlike Ozempic and Mounjaro, which target one or two hormone receptors, it acts on three pathways involved in appetite, blood sugar regulation and energy metabolism.

In a communication to News9 Digital, Dr Himika Chawla, Senior Consultant Endocrinologist and Diabetologist at PSRI Hospital, New Delhi, explains the drug’s weight-loss potential, possible side effects and relevance for India.

What is retatrutide and how does it work?

“Retatrutide is an experimental injectable medication developed by Eli Lilly. It is administered once a week and is known as a triple hormone receptor agonist. It targets three pathways involved in regulating appetite, blood sugar and energy balance: GLP-1, GIP and glucagon,” explained Dr Himika Chawla.

“GLP-1 helps regulate appetite and blood sugar, while GIP plays a role in insulin secretion and energy balance. Glucagon is involved in blood sugar regulation and energy metabolism. By targeting all three receptors simultaneously, retatrutide takes a different approach from existing weight-management medicines,” she added.

Obesity is a complex condition. It involves several biological mechanisms, and targeting more than one pathway may help produce greater weight loss, said Dr Chawla.

How much weight can retatrutide help people lose?

A phase 2 clinical trial published in The New England Journal of Medicine in 2023 studied 338 adults with obesity or overweight and a weight-related medical condition. After 48 weeks, participants receiving the highest dose of 12 mg lost an average of 24.2 per cent of their body weight, compared with 2.1 per cent in the placebo group.

Phase 3 findings have also reported substantial reductions. In the TRIUMPH-1 trial, participants without diabetes lost an average of 17.6 per cent, 23.7 per cent and 25 per cent of their body weight with the 4 mg, 9 mg and 12 mg doses, respectively, over 80 weeks. In TRIUMPH-2, participants with type 2 diabetes receiving 12 mg lost an average of 20.8 per cent over 80 weeks, alongside improvements in blood sugar control, stated the doctor.

“These findings are encouraging. However, I would caution against assuming that everyone taking retatrutide will lose a quarter of their body weight,” Dr Chawla said in her assessment of the results.

The figures represent trial averages, not guaranteed outcomes. Individual responses can vary, and participants received medical supervision and lifestyle guidance.

Retatrutide vs Ozempic vs Mounjaro: Key differences

Explaining about the key differences, Dr Himika said Ozempic contains semaglutide, which targets the GLP-1 receptor, while Mounjaro contains tirzepatide, which acts on GLP-1 and GIP receptors. Retatrutide targets all three, including glucagon.

Adding glucagon receptor activity could provide another way to influence energy metabolism and body weight. However, weight-loss percentages from separate trials cannot establish which medicine is superior because the studies involve different participants, doses and treatment durations. Head-to-head trials are needed for a reliable comparison.

Why retatrutide matters for India

Obesity and type 2 diabetes frequently occur together in India. Metabolic risks can develop at lower BMI levels than those traditionally used in some Western populations. Abdominal fat can contribute to insulin resistance and increase the risk of diabetes, high blood pressure, abnormal cholesterol levels and cardiovascular disease, Dr Himika said.

Assessing metabolic health therefore requires consideration of waist circumference, blood sugar, blood pressure, cholesterol levels, family history and existing medical conditions, rather than body weight alone, she added further.

If approved for appropriate indications in India, retatrutide could potentially offer another treatment option. Its effectiveness across Indian populations and affordability would also need consideration, particularly because obesity management may require sustained care.

What are the possible side effects?

Clinical trials have associated retatrutide with nausea, diarrhoea, constipation and vomiting, with gastrointestinal effects generally more common at higher doses. Phase 3 research has also reported dysesthesia, or altered skin sensations. Earlier research observed changes in heart rate, including an increase during treatment followed by a subsequent decline.

“Persistent vomiting or diarrhoea can cause dehydration. With substantial weight loss, there is also the possibility of losing lean body mass along with fat,” the doctor explained in discussing the concerns associated with weight-loss treatment.

Gallbladder complications and pancreatitis are additional safety concerns considered with incretin-based treatments. Further research is needed to establish the extent of these risks with retatrutide and clarify its long-term safety.

Can retatrutide replace diet, exercise or weight-loss surgery?

“No. Obesity is influenced by genetics, hormones, sleep, dietary habits, physical activity, medications and environmental and psychological factors. Medication can support weight management but does not replace comprehensive care,” stated Dr Himika, adding that balanced nutrition, regular physical activity, adequate sleep and behavioural support remain important. People with diabetes may also need reviews of their blood sugar levels and existing medicines as their weight changes.

“Bariatric surgery remains an established option for appropriately selected people with severe obesity. However, surgery and retatrutide have different mechanisms, risks, eligibility criteria and long-term considerations. Treatment decisions depend on overall health, obesity severity, existing complications and individual goals,” she said.

Is retatrutide available in India?

As of October 2026, retatrutide remains investigational and is not approved for routine use. Its availability will depend on regulatory review and approval in each country.

She said patients should avoid products marketed as retatrutide outside authorised clinical research because their composition, quality and safety may not be established. Promising clinical trial results do not make an experimental drug suitable for unsupervised use.

What does the future hold?

Retatrutide’s three-receptor action and substantial weight reductions reported in clinical trials make it a promising candidate in obesity treatment. However, long-term safety, sustained weight management, affordability and the effects of stopping treatment require further study, Dr Himika warned.

The ultimate measure of success will be whether treatment helps people maintain a healthier weight, improve metabolic health and reduce complications over time.