A new kind of experimental medication called retatrutide is yielding impressive blood sugar and weight loss results for people with type 2 diabetes, according to the drugmaker, Eli Lilly.
Retatrutide is a “triple G” medication that targets three metabolism-regulating hormones, which is one or two more than its rivals Ozempic and Mounjaro.
These study results are “unprecedented,” says Gitanjali Srivastava, MD, the medical director of Vanderbilt Obesity Medicine in Nashville, Tennessee, who wasn’t involved in retatrutide’s development.
The findings build on clinical trial results announced in December 2025, which found that retatrutide helped people with obesity lose nearly a third of their body weight (around 70 pounds [lb]).
Retatrutide Is a First-in-Its-Class Medication
Retatrutide is a triple agonist medication, meaning it works on three different hormone receptors in the body: GLP-1, GIP, and glucagon — leading some experts to call it a triple-G drug.
This is in contrast to its rival diabetes injectable drug semaglutide (Ozempic), a GLP-1 receptor agonist that targets one hormone. Another competitor, tirzepatide (Mounjaro), is a dual GIP/GLP-1 receptor agonist targeting two hormones.
“GLP-1 and GIP primarily work by reducing appetite and improving insulin secretion,” says Christine Bonarrigo, PharmD, a weight management pharmacist at Tufts Medical Center in Boston.
“What differentiates retatrutide is the addition of glucagon receptor activity, which appears to increase energy expenditure and fat oxidation. So instead of just helping patients eat less, this therapy may also help them burn more calories, essentially targeting both sides of the energy balance equation,” says Bonarrigo.
Type 2 diabetes and obesity often overlap, making it important to treat both conditions in patients, says Mir Ali, MD, the medical director of MemorialCare Surgical Weight Loss Center in Fountain Valley, California. “Since diabetes and obesity involve complex interactions between various hormones, finding the most effective combination to combat these conditions remains a primary clinical goal,” he says.
Retatrutide Led to Significant Blood Sugar and Weight Reductions
The phase 3 clinical trial, called TRANSCEND-T2D-1, enrolled more than 500 adults with type 2 diabetes who were not able to manage their blood sugar with diet and exercise alone. Participants had lived with diabetes for around 2.5 years when the trial began, and had not taken any medications to treat their condition for at least 90 days.
Adults were randomly assigned to receive 4 milligrams (mg), 9 mg, or 12 mg of retatrutide, or a placebo, in the form of a once-weekly injection. Those assigned to higher doses worked their way up to the highest dose.
At the end of the 40-week study, participants taking retatrutide achieved an average A1C reduction of up to 2 percent. A1C refers to a blood test that measures average blood sugar levels over the previous two to three months.
They also lost up to 36.6 lb on average, or 16.8 percent of their starting body weight. Weight loss continued through the end of the treatment period.
Retatrutide Side Effects Are Similar to Existing Diabetes and Obesity Injectables
The most common side effects for retatrutide were:
- Nausea (16 to 27 percent of participants, depending on dosage, compared with 3.7 percent of those taking a placebo)
- Diarrhea (19 to 23 percent, compared with 5 percent taking a placebo)
- Vomiting (16 to 18 percent, compared with 2 percent taking a placebo)
- Nerve issues (2 to 4 percent, compared with none taking a placebo)
Between 2 and 5 percent of participants on retatrutide stopped taking it before the trial ended, with a greater risk of stopping among those who took the highest dose. No one taking placebo quit the trial early.
How Retatrutide Stacks Up Against Other Medications
Retatrutide was not tested against semaglutide and tirzepatide in this phase 3 clinical trial, making it difficult to say how these drugs compare to one another. “Direct clinical trials comparing these different medications will be necessary,” Dr. Ali says.
Semaglutide and tirzepatide, however, have been compared head-to-head.
The new retatrutide trial showed A1C reductions up to 2 percent in less than a year, which is more than the current medications on the market. But Christoph Buettner, MD, PhD, the chief of the division of endocrinology at Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey, says that’s not a huge increase from tirzepatide.
“One might have expected a more pronounced improvement in glycemic control, given the degree of weight reduction,” he says.
Retatrutide Is Still Being Studied
Lilly is still studying retatrutide; the drug is not yet approved by the U.S. Food and Drug Administration (FDA) for use by the general public.
The company has multiple phase 3 clinical trials running to see how well retatrutide treats health conditions that often overlap with obesity, including knee osteoarthritis, moderate to severe obstructive sleep apnea, chronic low back pain, cardiovascular and renal outcomes, and liver disease.
“This could provide another significant treatment option for patients living with diabetes or obesity,” Ali says. Dr. Srivastava agrees. “Retatrutide could redefine standards for both diabetes and obesity care, offering patients deeper, more comprehensive metabolic improvements than previously possible,” she says.