Eli Lilly’s experimental drug, retatrutide, is showing remarkable promise beyond just weight loss and diabetes management. Recent Phase 3 studies indicate the therapy provides significant benefits across a range of interconnected health conditions, including knee osteoarthritis pain and obstructive sleep apnea.
Retatrutide's Impact on Obesity and Related Conditions
The findings, presented at the American Diabetes Association’s Scientific Sessions and published in The Lancet, come from two key trials: the TRIUMPH-1 obesity study and the TRANSCEND-T2D-1 diabetes study.
Significant Weight Reduction
- In the 80-week TRIUMPH-1 study, participants receiving the highest 12 mg dose of retatrutide achieved an average weight loss of 70.3 pounds, representing 28.3% of their body weight.
- A substantial 65.3% of participants on this dose reached a body mass index (BMI) below 30, with 33.3% achieving a BMI below 25, considered a normal range.
Improvements in Co-morbidities
Beyond weight, retatrutide demonstrated efficacy in several other areas:
- Knee Osteoarthritis Pain: Dedicated sub-studies showed a reduction in knee osteoarthritis pain scores by up to 73.1%.
- Obstructive Sleep Apnea: The severity of moderate-to-severe obstructive sleep apnea, measured by the apnea-hypopnea index, improved by up to 60.6%.
Benefits for Type 2 Diabetes Patients
The TRANSCEND-T2D-1 study, involving adults with type 2 diabetes, also yielded positive results:
- Participants saw HbA1c reductions of up to 2 percentage points from a baseline of 7.9% after 40 weeks of treatment.
- Up to 90% achieved HbA1c levels below 7%, and up to 46% reached levels below 5.7%, which is the threshold for normal blood sugar.
- Patients on the 12 mg dose lost an average of 36.6 pounds, or 16.8% of their body weight.
Cardiovascular Risk Markers
Both studies reported improvements in several cardiovascular risk markers. In the obesity study, retatrutide reduced triglycerides by up to 41%, non-HDL cholesterol by up to 24.2%, and systolic blood pressure by up to 12.3 mmHg. Similar positive trends were observed in the diabetes study.
“Obesity drives more than 200 downstream diseases, yet we have historically treated those conditions one at a time and in silos,” said Ania Jastreboff, professor of medicine and pediatrics at Yale School of Medicine and lead investigator of the studies. “In TRIUMPH-1 and TRANSCEND-T2D-1, treatment with retatrutide resulted in substantial weight reduction together with clinically meaningful improvements in glycemia, knee osteoarthritis pain, and obstructive sleep apnea.”
Kenneth Custer, executive vice president and president of Lilly Cardiometabolic Health, echoed this sentiment, highlighting the drug's broad impact across both trials.
Mechanism and Future Outlook
Retatrutide is a once-weekly triple hormone receptor agonist, targeting GIP, GLP-1, and glucagon receptors. Eli Lilly is actively studying the drug for a wide array of conditions, including obesity, type 2 diabetes, sleep apnea, cardiovascular and renal outcomes, chronic low back pain, and metabolic dysfunction-associated steatotic liver disease.
While still under clinical development and not yet approved, the most commonly reported side effects were generally mild to moderate, including nausea, diarrhea, vomiting, and constipation, with most participants continuing treatment.