Results emphasize the potential of a once-weekly injection to broaden choices for weight management, A1C regulation, knee osteoarthritis relief, and obstructive sleep apnea improvement

/PRNewswire/ - The first phase 3 study outcomes for retatrutide, a new glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and glucagon triple hormone receptor agonist, were shared today. These outcomes showed beneficial effects for individuals with obesity and type 2 diabetes, along with gains in addressing related issues such as obstructive sleep apnea and knee osteoarthritis discomfort. The data were unveiled during a symposium at the 2026 Scientific Sessions of the American Diabetes Association (ADA) in New Orleans.

Nearly 90 percent of those with type 2 diabetes also contend with overweight or obesity. For many facing type 2 diabetes, attaining both A1C targets (a central indicator of average blood glucose levels) and notable weight reduction continues to pose challenges, highlighting the demand for fresh therapies that tackle both issues at once. Retatrutide works by engaging three natural hormones - GIP, GLP-1, and glucagon - to curb appetite, enhance insulin function, boost energy expenditure, and support fat breakdown.

Information from the TRANSCEND-T2D-1 and TRIUMPH-1 studies builds on encouraging phase 2 results for retatrutide.

TRANSCEND-T2D-1: Innovative Triple Hormone Agonist Delivers Average Weight Reduction of 36.6 Pounds in Type 2 Diabetes Patients

The phase 3 TRANSCEND-T2D-1 trial, also published concurrently in The Lancet, assessed the safety and performance of retatrutide alone in adults with recent type 2 diabetes diagnosis who showed insufficient blood sugar control (A1C from 7.0 percent to 9.5 percent) through diet and exercise without additional diabetes drugs. This randomized, double-blind, placebo-controlled study involved 537 adults with recent-onset type 2 diabetes (average duration 2.5 years) and BMI of 23 kg/m2 or higher. Over 40 weeks, participants received weekly injections of retatrutide at 4 mg, 9 mg, or 12 mg, or placebo.

The results indicated that retatrutide provided robust glucose management, notable A1C drops, and considerable weight loss. Users saw A1C reductions up to 2 percent and body weight decreases of 16.8 percent (averaging 36.6 lbs lost). Additional benefits appeared in cardiovascular markers such as LDL cholesterol, triglycerides, and blood pressure. Side effects remained comparable to existing GLP-1 receptor agonists, with no fresh safety signals identified. Weight loss had not yet peaked by the 40-week mark.

"Weight loss with current medications tends to be smaller in people with type 2 diabetes than in those without it. Given that no prior trial has shown this level of weight reduction, retatrutide could substantially enhance outcomes for newly diagnosed patients through effective weight and blood glucose control," noted Harpreet Singh Bajaj, MD, MPH, the study's lead author. "This degree of weight loss may help slow disease advancement and transform approaches to type 2 diabetes care."

Researchers indicated that further extended phase 3 studies are in progress to compare retatrutide against semaglutide over 80 weeks (TRANSCEND-T2D-2) and to test retatrutide with insulin in chronic kidney disease patients over one year (TRANSCEND-T2D-3).

Highest Weekly Dose Yields Average 28.3 Percent Weight Loss at 80 Weeks in Obesity Patients

The phase 3 TRIUMPH-1 Obesity trial examined retatrutide's safety and impact on weight and overall health in adults with obesity or overweight. This randomized, placebo-controlled study enrolled 2,339 participants with obesity, including subgroups with knee osteoarthritis or obstructive sleep apnea. Participants received weekly retatrutide doses of 4 mg, 9 mg, or 12 mg, or placebo, across 80 weeks.

At the main endpoint, those on 9 mg and 12 mg retatrutide lost averages of 64.4 lbs (25.9 percent) and 70.3 lbs (28.3 percent), respectively. The 4 mg group, using a single dose step-up, averaged 47.2 lbs lost (19.0 percent), while 65.3 percent of the 12 mg group reached BMI below 30, exiting the obesity range by week 80. Retatrutide also improved cardiovascular indicators including triglycerides, systolic blood pressure, and high-sensitivity C-reactive protein (hsCRP).

"Obesity affects nearly half of Americans and represents a chronic neurometabolic condition linked to more than two hundred related health issues. Addressing obesity effectively can yield lasting health gains. Retatrutide, the first triple hormone receptor agonist in phase 3 development for obesity, produced major weight reductions, with nearly two-thirds of participants falling below obesity thresholds," stated Ania M. Jastreboff, MD, PhD, professor at Yale and lead author. "Beyond substantial weight loss, retatrutide improved outcomes ranging from reduced knee pain and fewer sleep issues to better cardiometabolic readings, showing how obesity treatment can broadly enhance well-being."

Study authors highlighted ongoing phase 3 trials exploring retatrutide in obesity with type 2 diabetes (TRIUMPH-2) and obesity with cardiovascular disease (TRIUMPH-3).

Research Presentation Details

Results of First Phase 3 Study of Retatrutide, a GIP, GLP-1, and Glucagon Receptor Agonist in Patients with T2D (TRANSCEND-T2D-1)

Harpreet Singh Bajaj, MD, MPH
Symposium: Unlocking the Next Frontier in Treatment of Obesity and Type 2 Diabetes with Retatrutide: A Triple Agonist, Activating the GIP, GLP-1 and Glucagon Receptors (TRANSCEND-T2D-1 and TRIUMPH-1 Results)
Saturday, June 6 from 1:55-2:15 p.m. CT
Ernest N. Morial Convention Center, Greater Hall A (Level 1)

Results of First Phase 3 Study of Retatrutide, a GIP, GLP-1, and Glucagon Receptor Agonist in Patients with Obesity (TRIUMPH-1)

Ania M. Jastreboff, MD, PhD
Symposium: Unlocking the Next Frontier in Treatment of Obesity and Type 2 Diabetes with Retatrutide: A Triple Agonist, Activating the GIP, GLP-1 and Glucagon Receptors (TRANSCEND-T2D-1 and TRIUMPH-1 Results)
Saturday, June 6 from 2:15-2:35 p.m. CT
Ernest N. Morial Convention Center, Greater Hall A (Level 1)

About American Diabetes Association's 2026 Scientific Sessions The ADA's 2026 Scientific Sessions, the world's largest scientific meeting focused on diabetes research, prevention, and care, will be held in New Orleans, LA, from June 5-8. Thousands of leading physicians, scientists, and healthcare professionals from around the world are expected to convene both in person and virtually to unveil cutting-edge research, treatment recommendations, and advances toward a cure for diabetes. Attendees will receive exclusive access to thousands of original research presentations and take part in provocative and engaging exchanges with leading diabetes experts. Join the Scientific Sessions conversation on social media using #ADASciSessions.

About American Diabetes Association The American Diabetes Association (ADA) is the nation's leading voluntary health organization fighting to end diabetes and helping people thrive. This year, the ADA celebrates 85 years of driving discovery and research to prevent, manage, treat, and ultimately cure diabetes - and we are not stopping. There are over 155 million Americans living with diabetes or prediabetes. Through advocacy, program development, and education, we are fighting for them all. To learn more or to get involved, visit us at diabetes.org or call 1-800-DIABETES (800-342-2383). Join us in the fight on Facebook (American Diabetes Association), Spanish Facebook (Asociacion Americana de la Diabetes), LinkedIn (American Diabetes Association), and Instagram (@AmDiabetesAssn). To learn more about how we are advocating for everyone affected by diabetes, visit us on X (@AmDiabetesAssn).

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SOURCE American Diabetes Association