SURMOUNT-2 results published in The Lancet show tirzepatide achieved a mean weight reduction of 15.7% at the highest dose (15 mg) in adults with obesity or overweight and type 2 diabetes

The data were presented during a symposium at the American Diabetes Association's (ADA) 83rd Scientific Sessions and were simultaneously published in The Lancet.

Tirzepatide met both co-primary endpoints and all key secondary endpoints compared to placebo for both estimands, with those taking tirzepatide achieving a mean weight reduction of 13.4% (29.8 lb. or 13.5 kg) on 10 mg and 15.7% (34.4 lb. or 15.6 kg) on 15 mg compared to 3.3% (7.0 lb. or 3.2 kg) on placebo for the efficacy estimand, which evaluates the treatment effect if all participants adhered to treatment. For the efficacy estimand, 81.6% (10 mg) and 86.4% (15 mg) of people taking tirzepatide achieved at least 5% body weight reduction, compared to 30.5% of those taking placebo.

Both doses of tirzepatide achieved all key secondary endpoints at 72 weeks of treatment for the efficacy estimand, including: i.Percentage of participants taking the 15 mg tirzepatide dose achieving greater than 15% and greater than 20% body weight reductions: 51.8% ( greater than 15% reduction) and 34.0% (greater than 20% reduction), compared to 2.6% and 1.0% with placebo. ii. Percentage of participants achieving A1C of less than 5.7%: 55.3% (10 mg) and 50.2% (15 mg), compared to 2.8% with placebo. iii. Reduction in waist circumference: 11.2 cm (10 mg) and 13.8 cm (15 mg), compared to 3.4 cm with placebo. iv. Reduction in fasting glucose: 49.2 mg/dL (10 mg) and 51.7 mg/dL (15 mg), compared to 2.4 mg/dL with placebo.

Pooled tirzepatide doses (10 mg and 15 mg) resulted in significantly greater improvements compared to placebo in systolic blood pressure (-7.2 mmHg vs. -1.0 mmHg), fasting triglycerides (-28.6% vs. -5.8%), HDL-cholesterol (8.2% vs. 1.1%) and non-HDL-cholesterol (-6.6% vs. 2.3%).

"People living with type 2 diabetes in many cases have been exposed to excess weight for years and often face increased difficulties in achieving weight loss results, typically losing 30% less weight than those who have obesity without type 2 diabetes. They need options to help overcome those challenges and achieve meaningful weight reductions," said W. Timothy Garvey, MD, MACE, MABOM, Professor of Medicine at the University of Alabama at Birmingham (UAB), Director of the UAB Diabetes Research Center and Principal Investigator of SURMOUNT-2. "Tirzepatide not only helped people achieve body weight reductions of up to 15.7%, but also helped to significantly lower A1C without severe hypoglycemia and led to improvements in other cardiometabolic endpoints.".

Additionally, tirzepatide met the co-primary and all key secondary endpoints for the treatment-regimen estimand, which represents the average results of all study participants regardless of treatment adherence, including: i. Mean body weight reductions: 12.8% (10 mg), 14.7% (15 mg), 3.2% (placebo). ii. Percentage of participants achieving body weight reductions of greater than 5%: 79.2% (10 mg), 82.8% (15 mg), 32.5% (placebo). iii. Percentage of participants achieving at least greater than 20% body weight reduction: 21.5% (10 mg) and 30.8% (15 mg), compared to 1.0% with placebo. iv. Percentage of participants achieving A1C of less than .7%: 46.0% (10 mg) and 48.6% (15 mg), compared to 3.9% with placebo.

The overall safety profile of tirzepatide was consistent with previously reported SURMOUNT and SURPASS trials and similar to incretin-based therapies approved for the treatment of obesity and overweight. The most commonly reported adverse events were gastrointestinal-related and were generally mild to moderate in severity, and usually occurred during the dose-escalation period. For those treated with tirzepatide (10 mg and 15 mg, respectively), nausea (20.2%, 21.9%), diarrhea (19.9%, 21.5%), vomiting (10.9%, 13.2%) and constipation (8.0%, 9.0%) were more frequently reported compared to placebo (6.3% [nausea], 8.9% [diarrhea], 3.2% [vomiting], 4.1% [constipation]).

Regulatory action for the U.S. submission for tirzepatide in adults with obesity, or overweight with weight-related comorbidities is expected by the end of 2023.

See -"Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase III trial"- Prof W Timothy Garvey, MD , Juan P Frias, MD, Ania M Jastreboff, MD, Prof Carel W le Roux, MD, Prof Naveed Sattar, MD, Diego Aizenberg, MD, et al. Published: The Lancet.June 26, 2023DOI:https://doi.org/10.1016/S0140-6736(23)01200-X.