Retatrutide Vs Ozempic: Next-generation Jab Doubles Weight Loss In Trial

News india Retatrutide Vs Ozempic: Next-generation Jab Doubles Weight Loss In Trial

Last Updated:October 31, 2026, 12:50 IST

In the first head-to-head Phase 3 trial, Eli Lilly's “retatrutide” cut weight by up to 21% compared with about 9% on Ozempic

Ozempic may have a stronger rival. An experimental weekly injection – Eli Lilly’s “retatrutide" – may be the most potent weight-loss drug yet. In a new trial, it helped people with type 2 diabetes lose an average of 20 kg, more than double the loss with Ozempic.

Retatrutide isn’t yet approved anywhere in the world, India included. Lilly announced the results of TRANSCEND-T2D-2, a Phase 3 trial, on October 28. Phase 3 is the last stage of testing before a company asks regulators for approval. This is the first time retatrutide has been tested directly, or “head-to-head", against an existing drug of its kind instead of a dummy injection.

What The Trial Found? 

The trial enrolled 1,298 adults with type 2 diabetes. Their blood sugar wasn’t under control on metformin, alone or combined with a sodium-glucose cotransporter-2 (SGLT2) inhibitor. On average, they weighed 102.4 kg. Each was given one of three weekly injections for 80 weeks, about 18 months: retatrutide 9 mg, retatrutide 12 mg, or Ozempic 2 mg. Ozempic is Novo Nordisk’s brand of semaglutide, and 2 mg is the highest dose approved in the US for type 2 diabetes.

People on retatrutide lost an average of 20.1 kg (19.5%) on the 9 mg dose and 21.5 kg (20.9%) on the 12 mg dose. People on Ozempic lost 9.5 kg (9.4%). Put simply, a person weighing 100 kg would lose about 20 kg on retatrutide and about 9 kg on Ozempic.

Blood sugar control improved too. Doctors track it with HbA1c (glycated haemoglobin), which reflects a person’s average blood sugar over about three months. Participants started at an average HbA1c of 8.3%. Both retatrutide doses brought it down by 2.2 percentage points, against 1.8 points on Ozempic. Doctors generally aim for an HbA1c below 7% in people with diabetes. Lilly said retatrutide also improved some heart-risk markers more than Ozempic did: non-HDL (“bad") cholesterol, triglycerides and systolic blood pressure.

“In TRANSCEND-T2D-2, the first Phase 3 trial comparing retatrutide with another incretin medicine, retatrutide delivered greater A1C reduction and more than double the weight loss of the highest dose of Ozempic approved in the U.S. for type 2 diabetes," said Kenneth Custer, Executive Vice President and President of Lilly Cardiometabolic Health in the press release.

Why Are Doctors Impressed?

Dr Anoop Misra, chairman, Fortis C-DOC Hospital for Diabetes and Allied Sciences, said the trial design itself gives the results weight. “This is the first Phase 3 head-to-head of retatrutide against an established incretin. It used semaglutide 2 mg, the top approved T2D dose, not a straw-man comparator. One does not know how it will perform against Tirzepatide or Mounjaro," he said.

“About 20–21% loss in a T2D population is striking. People with diabetes usually lose noticeably less than non-diabetic people on the same agent. Retatrutide more than doubled semaglutide’s 9.4%."

Dr Ambrish Mithal, chairman and head, endocrinology and diabetes, Max Healthcare, said the finding was “entirely along expected lines" and also a real achievement. “Getting about 20 kg weight loss in people with diabetes is a huge challenge," he said. “Remember, with both tirzepatide and semaglutide, the weight loss in people with diabetes is significantly less than in those without diabetes."

On blood sugar, Dr Misra was more measured. “The A1C gap is about 0.4%. That is real but modest."

How Does The ‘Triple’ Drug Work? 

Drugs like Ozempic copy a gut hormone called GLP-1 (glucagon-like peptide-1). It helps the pancreas release insulin after meals and tells the brain the stomach is full. Tirzepatide, sold as Mounjaro, copies two hormones: GLP-1 and GIP (glucose-dependent insulinotropic polypeptide).

Retatrutide goes a step further. It is a single molecule that acts on three hormone receptors: GLP-1, GIP and glucagon. That is why it’s called a “triple agonist". Scientists think the glucagon part helps the body burn more energy, which adds to the appetite-curbing effect of the other two.

What Earlier Studies Showed? 

The new results follow a run of published research. A Phase 2 trial in the New England Journal of Medicine in 2023 studied people with obesity but no diabetes. Those on the highest dose lost an average of 24.2% of their body weight in 48 weeks. A parallel Phase 2 study of people with type 2 diabetes, in The Lancet, found HbA1c fell by up to 2.02% and weight by about 17% over 36 weeks.

In June 2026, The Lancet published TRANSCEND-T2D-1, the first Phase 3 trial of retatrutide in diabetes. It ran at sites in the US, Mexico and India. In 537 adults whose diabetes was managed with diet and exercise alone, HbA1c fell by up to 1.94% and weight by up to 15.3% over 40 weeks.

There’s still no direct comparison with tirzepatide or Mounjaro. In the SURMOUNT-5 trial, published in the New England Journal of Medicine in 2025, tirzepatide cut weight by 20.2% against 13.7% for semaglutide in people without diabetes. Lilly says it is now testing retatrutide head-to-head against tirzepatide in an ongoing Phase 3 trial, TRIUMPH-5.

Side Effects

As with other drugs in this class, the most common side effects affected the stomach and gut. Diarrhoea affected 28% and 32% of people on the 9 mg and 12 mg doses of retatrutide, against 26% on Ozempic. Nausea affected 21% and 24%, against 21%, and vomiting 10% and 15%, against 13.2%. Constipation was less common with retatrutide: 14.2% and 13.1%, against 19.8% on Ozempic.

Dysesthesia, an unusual tingling or burning feeling on the skin, affected 5% and 6.5% on retatrutide against 2.7% on Ozempic. Lilly said most side effects were mild to moderate and usually went away during treatment. More people stopped retatrutide because of side effects: 4.8% on 9 mg and 7.9% on 12 mg, against 2.7% on Ozempic.

The Caveats

These are topline results from a company’s press release, and full data has not yet been peer-reviewed — meaning not seen by a group of neutral researchers. Lilly says detailed results will be presented at a medical meeting and published in a journal. The trial was also “open-label", meaning participants and doctors knew which drug each person was getting.

Dr Mithal said the comparison drug was given at its diabetes dose, which is lower than the dose used for weight loss. “They have compared it with 2 milligrams of semaglutide, which is actually the dose reserved for diabetes. For people with obesity, the dose goes up to 2.4, and we are soon going to see 7.2 semaglutide," he said. “An actual comparison ultimately will be of retatrutide with 7.2 semaglutide. That would be of great interest because that is the maximum weight loss dose of semaglutide."

Dr Misra cautioned against declaring a winner too soon. “Retatrutide looks like the most potent weight-loss agent so far, tirzepatide included. But that conclusion rests on cross-trial comparison, not a direct test."

Retatrutide is not on the market in any country. Lilly’s release states: “Retatrutide is an investigational molecule and is not approved for use in India."

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Meemansa ShekhawatSub-editor

A Journalism graduate, Meemansa Shekhawat is a sub-editor at News18. Driven by a keen interest in news, she is a passionate writer with specialisation in national and international affairs. You can re...Read More

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