Late-Stage Trial Results Show Promise for Eli Lilly’s Tirzepatide as Treatment for Type 2 Diabetes
Topline results from the Phase III SURPASS-1 trial show that a 40-week treatment with Eli Lilly's tirzepatide led to significant reductions in A1c and body weight in adults with type 2 diabetes.
Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist developed by Eli Lilly for use in patients with diabetes. The SURPASS-1 trial randomly assigned patients with inadequately controlled type 2 diabetes to either once-daily tirzepatide 5 mg, 10 mg or 15 mg or placebo.
In the SURPASS-1 trial, once-daily treatment with tirzepatide over 40 weeks resulted in an A1c reduction of 2.07% from and led to reductions in body weight by 11% from baseline. Approximately 51.7% of patients in the tirzepatide arm achieved an A1C of less than 5.7%, a level observed in people without diabetes. These primary and key secondary endpoints of changes in A1c and body weight reductions, respectively, were significantly greater than in the placebo group.
These reductions in A1c and body weight are better than those observed with Novo Nordisk’s Ozempic and Rybelsus therapies. Novo, a clear competitor to Lilly in the diabetes space, recently received FDA approval for Ozempic as a therapy to reduce the risk of major adverse cardiovascular events in patients with type 2 diabetes.
"Tirzepatide delivered impressive A1C and weight reductions for people with type 2 diabetes in this trial, confirming and building upon the phase 2 data that were released in 2018," said Principal Investigator of SURPASS-1, Julio Rosenstock, M.D., Director of the Dallas Diabetes Research Center. "The study took a bold approach in assessing A1C targets. Not only did nearly 90% of all participants taking tirzepatide meet the standard A1C goal of less than 7 %, more than half taking the highest dose also achieved an A1C less than 5.7%, the level seen in people without diabetes – an unprecedented finding and unique endpoint in trials evaluating glucose-lowering agents."
Additionally, Eli Lilly said the drug’s overall safety profile was similar to the well-established GLP-1 receptor agonist class. The most common adverse events reported in the patients were gastrointestinal side effects. Treatment discontinuation rates due to adverse events were less than 7 percent in each tirzepatide treatment arm.
"Tirzepatide is the first dual GIP/GLP-1 receptor agonist to complete a phase 3 trial," according to a statement made by Mike Mason, President of Lilly Diabetes. "We are impressed by these initial results showing how tirzepatide performed in people with a relatively short duration of diabetes, and we look forward to seeing more results in people who are later in the course of diabetes in future studies from our robust SURPASS clinical trial program."
Approximately 34 million people in the U.S. and 463 million worldwide are living with diabetes. Type 2 diabetes accounts for up to 90% to 95% of all diabetes cases in the U.S., and without adequate control of the disease, patients can experience several debilitating complications, such as diabetic retinopathy.
Eli Lilly is currently developing 13 drugs to treat diabetes, all of which are undergoing investigation in Phase I through Phase III trials. In addition to tirzepatide, Eli Lilly has been investing time into studying Trulicity® (dulaglutide), another drug in the GLP-1 class, in the REWIND trial. So far, the trial has found that once-weekly injections of dulaglutide results in a 12% reduction in major cardiac events.
The Indianapolis-based pharmaceutical company also recently reported new data from a pre-planned primary outcome analysis from its Phase III monarchE trial of Verzenio (abemaciclib) in combination with standard adjuvant endocrine therapy for breast cancer. The data, presented at the Virtual San Antonio Breast Cancer Symposium, show abemaciclib was effective for decreasing the risk of breast cancer recurrence by up to 28.7% compared with standard adjuvant endocrine therapy. The 3% difference between the two groups was considered statistically significant. Eli Lilly has commented that it will submit its trial data to regulatory authorities by the end of 2020.