Topline results from a phase 3 trial evaluating tirzepatide (Lilly) in adults with type 2 diabetes showed superior HbA1c and body weight reductions compared with placebo.
Tirzepatide is an investigational dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that integrates the actions of both incretins into a single molecule. GIP is believed to complement the effects of GLP-1 receptor agonists.
The 40-week, double-blind, placebo-controlled SURPASS-1 trial compared the efficacy and safety of tirzepatide monotherapy to placebo in 478 adults with type 2 diabetes inadequately controlled with diet and exercise alone. Patients were randomized 1:1:1:1 to receive either tirzepatide 5mg, 10mg, or 15mg, or placebo administered subcutaneously once weekly.
Results showed that all 3 doses of tirzepatide achieved statistical significance in HbA1c (primary end point) and body weight reductions (key secondary end point) at week 40 from baseline. Using the efficacy-regimen estimand, tirzepatide demonstrated the following HbA1c and body weight reductions for the 5mg, 10mg, and 15mg doses vs placebo, respectively:
- HbA1c reduction: -1.87%, -1.89%, -2.07% vs +0.04%
- Weight reduction: -7.0kg, -7.8kg, -9.5kg vs -0.7kg
- Percentage of patients achieving HbA1c less than 7%: 86.8%, 91.5%, 87.9% vs 19.6%
- Percentage of patients achieving HbA1c less than 5.7%: 33.9%, 30.5%, 51.7% vs 0.9%
In the treatment-regimen estimand, tirzepatide achieved the following HbA1c and body weight reductions for the 5mg, 10mg, and 15mg doses vs placebo, respectively:
- HbA1c reduction: -1.75%, -1.71%, -1.69% vs -0.09%
- Weight reduction: -6.3kg, -7.0kg, -7.8kg vs -1.0kg
- Percentage of patients achieving HbA1c less than 7%: 81.8%, 78.3% vs 23.0%
- Percentage of patients achieving HbA1c less than 5.7%: 30.9%, 26.8%, 38.4% vs 1.4%
The most common adverse events reported with tirzepatide included nausea, vomiting, and constipation, which were mild to moderate in severity and usually occurred during the dose escalation period. Severe hypoglycemia or hypoglycemia less than 54mg/dL were not observed in the tirzepatide treatment arms.
“The study took a bold approach in assessing A1c targets,” said Julio Rosenstock, MD, Director of the Dallas Diabetes Research Center and Principal Investigator of SURPASS-1. “Not only did nearly 90 percent of all participants taking tirzepatide meet the standard A1c goal of less than 7 percent, more than half taking the highest dose also achieved an A1c less than 5.7 percent, the level seen in people without diabetes – an unprecedented finding and unique endpoint in trials evaluating glucose-lowering agents.”
Additional data from the SURPASS-1 study will be presented at the American Diabetes Association’s 81st Scientific Sessions.
For more information visit lilly.com.
Lilly’s tirzepatide significantly reduced A1C and body weight in people with type 2 diabetes. [press release]. Indianapolis, IN: Eli Lilly and Company; December 9, 2020.