Retatrutide Outperformed Ozempic on Glucose and Weight Loss in Diabetes Study, Though More Patients Stopped Treatment

Eli Lilly said its experimental medicine retatrutide reduced blood sugar more than Novo Nordisk’s Ozempic at the highest approved dose and led to more than twice the weight loss in a head-to-head study involving adults with type 2 diabetes. But the results also came with a downside: more participants stopped retatrutide because of side effects.

The data came from TRANSCEND-T2D-2, a Phase 3 trial that enrolled 1,298 adults whose diabetes was not adequately controlled with metformin, with or without an SGLT2 inhibitor. Volunteers were randomly assigned to retatrutide 9 mg, retatrutide 12 mg, or Ozempic 2 mg. Lilly released the results as topline data, and the full study has not yet appeared in a peer-reviewed journal.

For many people living with type 2 diabetes, the trial provides an early comparison between a possible next-generation therapy and a medicine already in wide use. It does not alter current treatment choices. Retatrutide has not been approved by any regulator, and Lilly’s patient guidance says no one can legally sell it for human use.

What the Study Showed

After 80 weeks, both retatrutide doses lowered A1C, a measure of average blood sugar, by 2.2 percentage points from a starting average of 8.3%, compared with a 1.8-point drop for Ozempic. Participants taking retatrutide lost an average of 44 to 47 pounds, or about 19.5% to 20.9% of body weight, versus roughly 21 pounds, or 9.4%, with Ozempic. Lilly also said retatrutide improved non-HDL cholesterol, triglycerides and systolic blood pressure more than Ozempic.

The main objective was to show that the 12 mg dose was at least as effective as Ozempic in lowering A1C. That dose also met the trial’s most stringent statistical test. The 9 mg dose showed an A1C benefit that was described as nominal, meaning it did not meet that higher statistical threshold, according to BioPharma Dive’s reporting on the study.

“Head-to-head trials show patients and physicians how a potential new medicine compares with treatments that are available and reimbursed today,” said Kenneth Custer, Ph.D., executive vice president and president of Lilly Cardiometabolic Health. Lilly says retatrutide targets three hormone pathways — GIP, GLP-1 and glucagon — while Ozempic acts on GLP-1 alone.

Lilly said this was the sixth Phase 3 study in which retatrutide achieved its primary goals, and the first Phase 3 trial to compare it with another incretin medicine. Some earlier obesity studies reported larger average weight loss, but those compared the drug with placebo rather than an active treatment.

Tolerability Remained the Main Concern

Side effects are likely to be the most closely watched part of the results. Discontinuation because of adverse events was 7.9% with the 12 mg dose and 4.8% with the 9 mg dose, versus 2.7% with Ozempic. In other words, people on the highest retatrutide dose were nearly three times as likely to stop treatment because of side effects.

Digestive symptoms were the most common. Diarrhea occurred in 32.7% of people on the 12 mg dose, compared with 26.4% on Ozempic, while vomiting affected 15.0% versus 13.2%. Nausea rates were similar for the 9 mg dose and Ozempic. Dysesthesia, an unusual or unpleasant skin sensation, was reported in 6.5% of people on 12 mg compared with 2.7% on Ozempic. Lilly said most adverse effects were mild to moderate and generally resolved during treatment.

The study also had limitations. It was open-label, so participants and investigators knew which drug was being used. Lilly reported the findings using an “efficacy estimand,” which estimates outcomes as if participants had remained on the study drug. That method can make results appear stronger than what is seen in routine practice, where some people discontinue treatment. The trial was funded by the company, and independent researchers have not yet reviewed the complete dataset.

Who the Results May Matter to Most

The findings are most relevant for adults with type 2 diabetes who also have substantial excess weight. People with higher cardiovascular risk may also pay attention to the cholesterol and blood pressure changes, although the study was not designed to determine whether the drug lowers the risk of heart attack or stroke. The higher dropout rate suggests the drug may not be suitable for everyone, particularly those who already have trouble tolerating digestive side effects from existing GLP-1 medicines.

Wall Street is watching the drug closely. Leerink analyst David Risinger wrote in a client note that the results “strengthen the case for retatrutide’s long-term differentiation.” Even so, approval is not assured, and questions remain about pricing and insurance coverage.

For consumers, the most immediate danger is the gray market. Lilly says anyone selling retatrutide to customers is breaking the law. In August, the company sued six businesses it accused of selling counterfeit, unapproved versions, according to Healio’s reporting on the lawsuits. Products marketed online as retatrutide may contain unknown ingredients, contaminants or the wrong dose, and no clinical result can eliminate those risks.

People currently using Ozempic, Mounjaro or another diabetes medication should not stop or change treatment because of these findings. Those interested in future options can ask their clinician whether they might qualify for an ongoing clinical trial.

Lilly says detailed TRANSCEND-T2D-2 findings will be presented at a future medical meeting and published in a peer-reviewed journal. The company also says it plans to seek U.S. approval in the first quarter of 2027, and a separate head-to-head study against its own tirzepatide is ongoing, according to BioSpace. Until regulators make a decision, retatrutide remains a promising but unproven option, with a clear trade-off between stronger results and more difficult side effects.

Frequently Asked Questions

What did the study find? After 80 weeks, retatrutide reduced A1C by 2.2 points compared with 1.8 for Ozempic 2 mg, and produced about 19.5% to 20.9% weight loss versus 9.4%.

Were side effects more common? Yes. Treatment discontinuation because of side effects was 7.9% with the 12 mg dose compared with 2.7% with Ozempic, and diarrhea and vomiting were more common at the highest dose.

Is retatrutide approved? No. It remains investigational and has not been approved by the FDA or any other regulator.

Can it be bought online? No legal seller exists. Lilly says anyone selling it to consumers is breaking the law, and such products may be unsafe.

Should I switch from Ozempic? No. Do not change diabetes treatment based on these results. Speak with your clinician about your options.

When might retatrutide become available? Lilly plans to seek FDA approval in the first quarter of 2027. Any approval would come later.