Two more phase 3 clinical trials of Eli Lilly’s tirzepatide in Type 2 diabetics have met their primary endpoints. The studies, like a trial that read out late last year, linked the dual GIP/GLP-1 agonist to significant declines in blood sugar and body weight.
In one of the clinical trials, SURPASS-3, investigators randomized 1,444 patients with Type 2 diabetes to receive titrated insulin degludec or one of three doses of tirzepatide. After 52 weeks, patients on the highest dose of tirzepatide, 15 mg, had experienced a 2.37% drop in A1C, a measure of blood sugar. A1C fell 1.34% in the control group. Baseline A1C was 8.17%. By the end of the study, almost half of patients on tirzepatide had an A1C of less than 5.7%, the level considered to be normal.
The other clinical trial, SURPASS-5, generated similar A1C data. In that study, investigators enrolled 475 adults with Type 2 diabetes that was inadequately controlled by insulin glargine, with or without metformin. Participants received placebo or one of three doses of tirzepatide on top of the titrated insulin glargine, with or without metformin, that they were taking before joining the study.
After 40 weeks, A1C in the tirzepatide arms had fallen by as much as 2.59% from a baseline of 8.31%, versus a drop of 0.93% in the control group. Almost two-thirds of patients on tirzepatide had A1C levels of less than 5.7%.
Both trials also generated evidence of the effect of tirzepatide on weight. In SURPASS-3, people on the highest dose of tirzepatide lost 12.9 kg, a decline of 13.9% from baseline. Patients in the control group gained 2.3 kg. Similarly, in SURPASS-5 patients on the highest dose of tirzepatide lost 10.9 kg, a decline of 11.6% from baseline. The control group added 1.7 kg over the course of the study.
As in the previous phase 3, Lilly said the most commonly reported adverse events in SURPASS-3 and SURPASS-5 were gastrointestinal-related and mild to moderate in severity. However, the drug was again associated with a higher rate of dropouts than the controls.
More than 10% of patients on the highest dose of tirzepatide discontinued treatment due to adverse events in SURPASS-3 and SURPASS-5. The dropout rate correlated to dose—6% to 7% of patients on 5 mg of tirzepatide stopped treatment—suggesting tolerability can be improved if patients are willing to accept somewhat lower levels of efficacy.
The three phase 3 clinical trials to read out in recent months are part of a big development program, the centerpiece of which is a 12,500-subject cardiovascular outcome study. If successful, the program will give Lilly a successor to Trulicity, which is set to lose patent protection in 2027, and a challenger to drugs sold by Novo Nordisk and other rivals for the diabetes market.