Even as Zepbound and Mounjaro fire on all cylinders and Foundayo gets off to the races in the oral market, Eli Lilly is keenly aware that the one-size-fits-all approach to obesity and diabetes treatment pioneered by early GLP-1s will soon be obsolete.
Now, in a detailed showing of the next incretin drug Lilly hopes to get across the regulatory finish line—the triple-G agonist retatrutide—the company is deepening the case for its asset to help a wide range of patients in need of chronic weight management, including those with Type 2 diabetes.
Diving deeper into the data in the late-stage weight loss trial called Triumph-1, Lilly is now adding context to the impressive figures reported earlier this year, which, at the highest level in an extension of the trial, reached a magnitude more often associated with bariatric surgery.
In that study, the highest dose of retatrutide, 12 mg, helped patients lose 28.3% of their weight on average after 80 weeks if they adhered to treatment as instructed. For a subset who extended treatment out to 104 weeks, patients on the 12-mg dose lost 30.3% of their weight on average using the same estimand.
In addition to looking at weight loss data, the trial included two “nested basket studies” to assess the drug’s effect in patients with osteoarthritis pain and moderate-to-severe obstructive sleep apnea.
In patients with knee osteoarthritis included in Triumph-1, retatrutide helped chart an up to 4.3-point, or 73.1%, reduction on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale from a baseline of 6.0.
And among those with moderate-to-severe obstructive sleep apnea in the study, Lilly’s triple agonist helped get patients down to 36.1 events per hour from a baseline of 58.6 events per hour on the apnea-hypopnea index (AHI).
Rachel Batterham, Lilly’s SVP of medical innovation and external engagement, who previously spent 25 years treating patients with diabetes and obesity as a practicing clinician, helped put the Triumph-1 results into perspective during a fireside chat with journalists at the American Diabetes Association 2026 Scientific Sessions on Saturday.
“Obesity is a disease of excess adiposity that impacts on nearly every organ in the body,” Batterham explained. “And my patients, the biggest thing would often be physical functioning, severe osteoarthritis,” she said of the significance of the basket study data. “Every step that you take is painful.”
The more than 70% reduction on the WOMAC pain scale, meanwhile, means “70% less pain every time you take a step,” she said, adding that this would likely make patients more mobile and “be able to go to work and to be able to enjoy life.”
Shining a light further on the sleep apnea analysis, Batterham noted that the endpoint there was looking at how many times per hour a sleep apnea patient’s blood oxygen level falls, causing them to wake up slightly.
“So, at baseline, people were waking up 60 times an hour, and to reduce that by 60%, can you imagine the impact that has on how the person feels the next day, their ability to function,” she noted.
Beyond Triumph-1, Lilly also used the ADA conference to offer a deeper glimpse at retatrutide's safety and efficacy in Type 2 diabetes, where the company reported topline results in March.
Further, Lilly broke out detailed data on the ability of retatrutide to simultaneously help patients chart improvements in certain cardiovascular risk factors in both its Type 2 diabetes and obesity studies, including waist circumference, non-HDL cholesterol, triglycerides, systolic blood pressure and high-sensitivity C-reactive protein (hsCRP).
In Triumph-1 specifically, retatrutide helped patients chart reductions of up to 41% in triglycerides, 24.2% in non-HDL cholesterol, 12.3 mmHg in systolic blood pressure and 9.5 inches in waist circumference at the 80-week mark.
As for Lilly’s late-stage retatrutide trial in Type 2 diabetes, Transcend-T2D-1, retatrutide triggered reductions of up to 39.6% in triglycerides, 19.8% in non-HDL cholesterol, 6.4 mmHg in systolic blood pressure, and 4.9 in (12.4 cm) in waist circumference at 40 weeks.
In Type 2 diabetes, Lilly previously reported that after 40 weeks of treatment, 4-mg, 9-mg and 12-mg doses of retatrutide demonstrated average reductions in A1C of 1.7%, 1.9% and 1.9%, respectively, when accounting for all patients in the trial.
In the new data unveiled Saturday, Lilly noted that upwards of 90% of patients on retatrutide achieved an A1C below 7.0%, which is the American Diabetes Association’s general target for Type 2 diabetes, and up to 85% of patients hit an A1C of 6.5% or below, which Lilly argued could make a case for setting more stringent blood sugar level lowering goals for Type 2 diabetes patients early in their treatment journey.
Moreover, up to 46% of participants achieved an A1C below 5.7%, which marks the threshold for normoglycemia.
Looking at the Transcend-T2D-1 results, patients on retatrutide were able to achieve “very stringent glycemic control levels,” Thomas Seck, SVP of product development for Lilly cardiometabolic health, said during the fireside chat.
Seck added that the weight loss figures in Transcend were also meaningful in the Type 2 diabetes study. Diabetes patients have more difficulty losing weight than those without the condition, the exec said, noting that the 16.8% average reduction seen on the highest retatrutide dose cut off at 40 weeks, failing the achieve the “full plateau” of reduction that might be achievable.
Seck did flag higher rates of urinary tract infections and dysesthesia in patients treated with retatrutide versus placebo, though he noted that these events were often “mild in intensity and typically do not lead to discontinuation,” which is a major pitfall for patient adherence to incretin medicines.
Nevertheless, the manuscript on the diabetes readout did point to other potential safety concerns, including seven cases of arrythmias in treated patients, plus three more who experienced major cardiovascular complications. No such events were logged in the placebo cohort of the 403-participant trial.
Seck did not seem too concerned about those issues, reminding the journalists present that “these are relatively small studies.”
“We continue to be confident in the profile of retatrutide, given the cardiovascular measures that we see around lipids, blood pressure and others, and we think that will manifest to hopefully reduction in cardiovascular risk, but it’s too early to judge based on the data we have with Transcend-1 and Triumph-1,” he explained.
Coming off the success of Zepbound and Mounjaro, Lilly is keenly aware that it can’t lean on one or two products forever, both for the sake of its business and in the interest of treating metabolic health holistically.
Lilly became a “two product company” in obesity this year with the green light for its oral GLP-1 orforglipron, now branded Foundayo, Ken Custer, EVP and president of Lilly cardiometabolic health, said during the fireside.
While Lilly expects retatrutide to mark its next incretin approval, the company more broadly anticipates having “as many as five approved obesity medicines” by the end of the decade, according to Custer. By meeting that goal, Lilly would be “bringing forward a suite of options for people and their healthcare providers to choose from,” Custer said.
Seck largely echoed that thinking, pointing to the need for a range of tools in the armamentarium.
“I think what’s really unique at Lilly right now is that we’re not focusing on one molecule and want to make sure every patient fits that one molecule, but we actually have some luxury to offer options,” he explained.