Retatrutide side effects in focus as drug outperforms Ozempic in diabetes trial

What the trial compared

TRANSCEND-T2D-2 was a head-to-head phase 3 study in adults with type 2 diabetes. It compared weekly injections of retatrutide at 9 mg or 12 mg with Ozempic (semaglutide) at 2 mg, according to Medscape. Reuters reported that Lilly chose the 2 mg Ozempic dose as the comparator because it is the highest approved dose available.

Retatrutide is often called a "triple-G" drug. It acts on three hormone receptors: GLP-1, GIP and glucagon. Semaglutide acts on GLP-1 only. Lilly released topline results on 28 October 2026 and said it will present the detailed findings at a future medical meeting.

Results for HbA1c and weight

After 80 weeks, both retatrutide doses lowered HbA1c (glycated haemoglobin, a measure of average blood sugar over time) by an average of 2.2 percentage points. Ozempic lowered it by 1.8 points. BioPharma Dive reported that Lilly called the 12 mg result a significant improvement over Ozempic. For the 9 mg dose, the company described the difference as statistically "nominal".

Average weight loss was 19.5% on retatrutide 9 mg and 20.9% on 12 mg, compared with 9.4% on Ozempic, Medscape reported. STAT noted that these figures come from analyses of participants who stayed on treatment, not from everyone who entered the trial. Lilly also reported larger improvements with retatrutide in non-HDL cholesterol, triglycerides and systolic blood pressure.

Novo Nordisk responded through Ambre James-Brown, head of its global media. She said Ozempic should not be judged on weight loss alone and that its highest doses have shown benefits for the heart, kidneys and liver, according to Reuters.

Retatrutide side effects reported in the trial

Medscape listed the most common adverse events on retatrutide 9 mg and 12 mg, compared with Ozempic 2 mg, as follows:

• Diarrhoea: 28.3% and 32.7%, against 26.4%
• Nausea: 21.2% and 23.8%, against 21.3%
• Constipation: 14.2% and 13.1%, against 19.8%
• Vomiting: 10.2% and 15%, against 13.2%
• Indigestion (dyspepsia): 10.4% and 8.5%, against 11.6%

Dysaesthesia, an abnormal or unpleasant skin sensation, affected 4.8% and 6.5% of people on the two retatrutide doses, compared with 2.7% on Ozempic. Urinary tract infections were reported in 5.8% and 4.2% on retatrutide and in 5.8% on Ozempic. According to Medscape, most events were mild to moderate and resolved during treatment.

The largest difference was in people who stopped treatment because of adverse events. This happened in 4.8% of people on retatrutide 9 mg and 7.9% on 12 mg, compared with 2.7% on Ozempic. This pattern matches earlier research. A 2025 review of phase 1 and 2 studies in Biomolecules described retatrutide's common adverse effects as mainly gastrointestinal and dose-related.

Approval status and online sales

Retatrutide remains investigational. Medscape reported that it has not been approved by the US Food and Drug Administration or any other regulatory body, yet it is being advertised for sale online. Lilly says anyone offering the drug to consumers is breaking the law, and the FDA has issued warning letters to some of the companies involved. BioPharma Dive described a "black market" for the drug.

According to Reuters, Lilly plans to seek US approval in 2027. It is also testing retatrutide against tirzepatide in TRIUMPH-5, an ongoing phase 3 trial in adults with obesity, with or without type 2 diabetes.

In South Africa, the semaglutide medicines registered with SAHPRA are Ozempic, Wegovy, Rybelsus, Extensior and Semagard. More detail on retatrutide's local position is in the retatrutide guide for South Africa. Approved semaglutide pens and their prices are listed on the Ozempic and Wegovy prices page. Questions about diabetes or weight treatment should go to a doctor or pharmacist. See the medical disclaimer.