Lilly’s retatrutide outperforms Ozempic on weight loss in diabetes trial; safety concerns remain
Eli Lilly’s experimental drug delivered greater weight loss and blood sugar reduction than Ozempic 2 mg in a Phase 3 trial.
US pharmaceutical major Eli Lilly reported that its experimental weight-loss and diabetes drug, retatrutide, achieved greater blood sugar reduction and more than double the weight loss of Novo Nordisk’s Ozempic 2 mg in a Phase 3 clinical trial. However, the findings are preliminary, and the drug remains unapproved for use in India or elsewhere.
In the 80-week TRANSCEND-T2D-2 trial involving 1,298 adults with type 2 diabetes, participants receiving retatrutide lost an average of 20.1 kg to 21.5 kg, depending on the dose, compared with 9.5 kg among those taking Ozempic 2 mg. Lilly announced the results on Wednesday (October 28).
Retatrutide also reduced glycated haemoglobin (HbA1c), a measure of average blood glucose levels over approximately three months, by 2.2 percentage points at both tested doses. Ozempic reduced HbA1c by 1.8 percentage points.
The findings could add to competition in the rapidly expanding market for medicines targeting diabetes and obesity. However, the results are based on the company's topline announcement, with detailed trial data yet to be published in a peer-reviewed journal or presented at a medical meeting.
Weight loss comes with tolerability concerns
Participants receiving the 9 mg dose of retatrutide lost an average of 19.5 per cent of their body weight, while those receiving 12 mg lost 20.9 per cent. The corresponding reduction with Ozempic was 9.4 per cent.
The results are notable because weight management can be more difficult for people with type 2 diabetes. However, the findings should not be interpreted as proof that retatrutide is superior across every clinically relevant outcome or patient group.
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The trial was open-label, meaning participants and investigators knew which treatment was being administered. This is an important consideration when interpreting clinical outcomes, although it does not by itself invalidate the results.
Safety and tolerability will also influence the drug's eventual clinical value. Diarrhoea occurred in 28.3 per cent of participants taking retatrutide 9 mg and 32.7 per cent of those receiving 12 mg, compared with 26.4 per cent among Ozempic users.
Nausea affected 21.2 per cent and 23.8 per cent of participants in the two retatrutide groups, respectively, compared with 21.3 per cent in the Ozempic group.
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More importantly, treatment discontinuation due to adverse events was higher with retatrutide. The rates were 4.8 per cent for the 9 mg dose and 7.9 per cent for the 12 mg dose, compared with 2.7 per cent for Ozempic.
The higher discontinuation rate at the 12 mg dose suggests that the additional weight-loss benefit may need to be assessed alongside treatment tolerability and patients' ability to remain on therapy.
Lilly also reported improvements in non-HDL cholesterol, triglycerides and systolic blood pressure. However, these findings do not establish that retatrutide reduces heart attacks, strokes or cardiovascular deaths. Such benefits require appropriate clinical outcome evidence.
What the findings mean for India
India represents a significant potential market for diabetes and obesity treatments, given the country's substantial burden of metabolic disease. However, the trial's results do not automatically establish how well retatrutide would perform in Indian patients or whether it would be affordable for widespread use.
The study enrolled adults whose type 2 diabetes was inadequately controlled with metformin, with or without an SGLT2 inhibitor. Participants had baseline HbA1c levels between 7 per cent and 10.5 per cent, and the average baseline body weight was 102.4 kg.
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The findings therefore relate to a specific patient population and should not be generalised to everyone seeking weight-loss treatment.
For India, regulatory approval, pricing, availability, long-term safety and access through routine healthcare will be critical considerations. Even if the medicine eventually receives approval, its high efficacy in a clinical trial would not necessarily translate into broad access.
Retatrutide is an investigational drug and is not approved for human use in India. Consumers should be cautious of online sellers claiming to offer the experimental molecule.
A crowded market, with more evidence still needed
Retatrutide is a once-weekly experimental medicine that activates three hormone receptors: GIP, GLP-1 and glucagon. This differentiates it mechanistically from semaglutide, the active ingredient in Ozempic, which acts on the GLP-1 receptor.
The TRANSCEND-T2D-2 study is the sixth Phase 3 trial of retatrutide to report positive topline results, according to Lilly. The company is also evaluating the drug across several conditions, including obesity, type 2 diabetes and cardiovascular risk.
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Nevertheless, the latest findings represent an interim milestone rather than a basis for immediate treatment decisions. Full trial results, longer-term safety data and regulatory assessments will be needed to determine whether retatrutide can deliver a meaningful clinical advantage over existing therapies.
For patients and healthcare providers in India, the central question is no longer just how much weight a new medicine can help people lose, but whether its benefits can be sustained safely and made accessible at a viable cost.
