Retatrutide: A New Treatment for Type 2 Diabetes and Weight Loss

A new experimental medication called retatrutide is demonstrating promising results in managing blood sugar levels and promoting weight loss for individuals with type 2 diabetes, according to its developer, Eli Lilly. In a 40-week late-stage clinical trial, participants experienced up to a 2% reduction in A1C blood sugar levels and lost nearly 17% of their initial body weight—averaging around 40 pounds—as reported in a company press release.^{1, 4}

What is Retatrutide?

Retatrutide is a first-in-class “triple G” medication, meaning it targets three metabolism-regulating hormones: GLP-1, GIP, and glucagon.¹ This differs from existing medications like semaglutide (Ozempic), which targets only one hormone (GLP-1), and tirzepatide (Mounjaro), which targets two (GIP and GLP-1).¹

How Does Retatrutide Work?

GLP-1 and GIP primarily function by reducing appetite and enhancing insulin secretion.¹ Retatrutide’s unique action lies in its inclusion of glucagon receptor activity, which appears to increase energy expenditure and fat oxidation. This suggests the therapy may help patients both reduce calorie intake and burn more calories, addressing both sides of the energy balance equation.¹

Clinical Trial Results: TRANSCEND-T2D-1

The phase 3 clinical trial, known as TRANSCEND-T2D-1, involved over 500 adults with type 2 diabetes who were unable to adequately control their blood sugar through diet and exercise alone.⁴ Participants had been living with diabetes for approximately 2.5 years and had not used diabetes medications for at least 90 days prior to the study.⁴

Participants were randomly assigned to receive weekly injections of 4 mg, 9 mg, or 12 mg of retatrutide, or a placebo.⁴ At the 40-week mark, those receiving retatrutide experienced an average A1C reduction of up to 2%.^{1, 4} They also lost up to 36.6 pounds (16.8% of their starting body weight) on average.^{1, 4} Weight loss continued throughout the treatment period.⁴

Side Effects

The most common side effects observed in the retatrutide trial were:

• Nausea (16% to 27% of participants, depending on dosage, compared to 3.7% on placebo)
• Diarrhea (19% to 23%, compared to 5% on placebo)
• Vomiting (16% to 18%, compared to 2% on placebo)
• Nerve issues (2% to 4%, compared to none on placebo)

Between 2% and 5% of participants taking retatrutide discontinued the trial, with a higher rate among those receiving the highest dose. No participants taking the placebo stopped the trial early.⁴

How Does Retatrutide Compare to Other Medications?

Currently, retatrutide has not been directly compared to semaglutide and tirzepatide in a head-to-head clinical trial.⁴ However, previous studies have compared semaglutide and tirzepatide. A 2025 study showed that adults with type 2 diabetes taking tirzepatide reduced their A1C levels by 1.3% over a year, while those taking semaglutide experienced a reduction of 0.9%.² The tirzepatide group also lost an average of 22 pounds (9% of starting weight), compared to 17 pounds (7% of starting weight) in the semaglutide group.²

The retatrutide trial demonstrated A1C reductions of up to 2% in less than a year, exceeding the results seen with current medications.⁴

What’s Next for Retatrutide?

Eli Lilly is continuing to study retatrutide in multiple phase 3 clinical trials to assess its effectiveness in treating conditions often associated with obesity, including knee osteoarthritis, moderate to severe obstructive sleep apnea, chronic low back pain, cardiovascular and renal outcomes, and liver disease.⁴

Retatrutide has not yet been approved by the U.S. Food and Drug Administration (FDA) for public apply.⁴

¹ https://www.lilly.com/news/stories/what-to-know-about-retatrutide

² https://www.cnbc.com/2026/03/19/eli-lillys-obesity-drug-retatrutide-clears-late-stage-diabetes-trial.html

⁴ https://www.biospace.com/press-releases/lillys-triple-agonist-retatrutide-demonstrated-significant-reductions-in-a1c-and-weight-in-first-phase-3-trial-for-treatment-of-type-2-diabetes