Results from two phase 3 trials evaluating tirzepatide (Lilly) in adults with type 2 diabetes demonstrated statistically significant HbA1c and body weight reductions.
Tirzepatide is an investigational once-weekly, 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 52-week open-label SURPASS-3 (ClinicalTrials.gov: NCT03882970) and 40-week double-blind SURPASS-5 (ClinicalTrials.gov: NCT04039503) trials evaluated the efficacy and safety of 3 doses of tirzepatide (5mg, 10mg, and 15mg) in adults with type 2 diabetes. SURPASS-3 (N=1444) compared tirzepatide to titrated insulin degludec in adults who had inadequate glycemic control on stable doses of metformin with or without an SGLT-2 inhibitor. SURPASS-5 (N=475) compared tirzepatide to placebo, in addition to titrated insulin glargine with or without metformin.
Findings from both studies showed that all 3 doses of tirzepatide demonstrated statistically significant reductions in HbA1c (primary end point) and body weight (key secondary end point).
In SURPASS-3, efficacy estimand results (which represents efficacy prior to discontinuation of study drug or initiating rescue therapy for persistent hyperglycemia) for tirzepatide 5mg, 10mg, and 15mg vs insulin degludec, respectively, included the following:
- HbA1c reduction (baseline of 8.17%): -1.93%, -2.20%, -2.37% vs -1.34%
- Weight reduction (baseline of 94.3kg): -7.5kg, -10.7kg, -12.9kg vs +2.3kg
- Percentage of patients achieving HbA1c less than 7%: 82.4%, 89.7%, 92.6% vs 61.3%
- Percentage of patients achieving HbA1c less than 5.7%: 25.8%, 38.6%, 48.4% vs 5.4%
In the treatment-regimen estimand (which represents the efficacy irrespective of adherence to the investigational drug or introduction of rescue therapy for persistent severe hyperglycemia), tirzepatide was associated with the following HbA1c and body weight reductions for the 5mg, 10mg, and 15mg doses vs insulin degludec, respectively:
- HbA1c reduction: -1.85%, -2.01%, -2.14% vs -1.25%
- Weight reduction: -7.0kg, -9.6kg, -11.3kg vs +1.9kg
- Percentage of patients achieving HbA1c less than 7%: 79.2%, 81.5%, 83.5% vs 58.0%
“Throughout the year-long study, tirzepatide provided sustained A1C reduction and progressive weight loss with low occurrence of level 2 hypoglycemia, an important consideration for people with diabetes and their clinicians,” said Bernhard Ludvik, MD, Associate Professor of Medicine, Landstrasse Clinic, Vienna, and principal investigator of SURPASS-3.
In SURPASS-5, efficacy-estimand results for tirzepatide 5mg, 10mg, and 15mg vs placebo, respectively, included the following:
- HbA1c reduction (baseline of 8.31%): -2.23%, -2.59%, -2.59% vs -0.93%
- Weight reduction (baseline of 95.2kg): -6.2kg, -8.2kg, -10.9kg vs +1.7kg
- Percentage of patients achieving HbA1c less than 7%: 93.0%, 97.4%, 94.0% vs 33.9%
- Percentage of patients achieving HbA1c less than 5.7%: 26.1%, 47.8%, 62.4% vs 2.5%
In the treatment-regimen estimand, tirzepatide led to the following HbA1c and body weight reductions for the 5mg, 10mg, and 15mg doses vs placebo, respectively:
- HbA1c reduction: -2.11%, -2.40%, -2.34% vs -0.86%
- Weight reduction: -5.4kg, -7.5kg, -8.8kg vs +1.6kg
- Percentage of patients achieving HbA1c less than 7%: 87.3%, 89.6%, 84.7% vs 34.5%
The safety profile of tirzepatide was similar to that seen with the GLP-1 receptor agonist class. The most common adverse events reported were gastrointestinal side effects that were generally mild to moderate in severity and decreased with continued dosing.
“Significantly lowering A1C levels and weight are high priorities throughout the type 2 diabetes treatment journey, and the results we have seen from 3 SURPASS studies to date fuel our belief in tirzepatide’s ability to meet those needs,” said Mike Mason, president, Lilly Diabetes.
Additional findings from the SURPASS-3 and SURPASS-5 trials will be presented at the American Diabetes Association’s® 81st Scientific Sessions®.
Tirzepatide significantly reduced A1C and body weight in people with type 2 diabetes in two phase 3 trials from Lilly’s SURPASS program. [press release]. Indianapolis, IN: Eli Lilly and Company; February 17, 2021.