INDIANAPOLIS—Eli Lilly and Co. has shared promising data from its SURPASS program, reporting that tirzepatide—its once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist—resulted in significant reductions in A1C and body weight in adults with type 2 diabetes in the SURPASS-3 and SURPASS-5 Phase 3 trials after 52 weeks and 40 weeks, respectively. SURPASS-3 was a 52-week randomized, open-label trial evaluating the efficacy and safety of tirzepatide at 5 mg, 10 mg and 15 mg compared to titrated insulin degludec in adults with type 2 diabetes who have inadequate glycemic control on stable doses of metformin with or without an SGLT-2 inhibitor. SURPASS-5 was a 40-week randomized, double-blind trial evaluating the efficacy and safety of tirzepatide at 5 mg, 10 mg and 15 mg compared to placebo, both as an add-on to titrated insulin glargine with or without metformin in adults with type 2 diabetes.
As noted in a press release, “Treatment differences for two estimands – efficacy and treatment-regimen – were evaluated for three tirzepatide doses (5 mg, 10 mg and 15 mg) versus the respective comparators for SURPASS-3 and SURPASS-5. Efficacy estimand represents efficacy prior to discontinuation of study drug or initiating rescue therapy for persistent severe hyperglycemia. Treatment-regimen estimand represents the efficacy irrespective of adherence to the investigational medicine or introduction of rescue therapy for persistent severe hyperglycemia.” The primary and key secondary endpoints were met for both estimands in SURPASS-3 and in SURPASS-5.
"For people with type 2 diabetes who are at the point in their treatment journey where they would progress to an injectable therapy, these positive results emphasize tirzepatide's potential to deliver a meaningful impact in lowering their A1C and weight," said Dr. Bernhard Ludvik, Associate Professor of Medicine, Landstrasse Clinic, Vienna, and principal investigator of SURPASS-3. "Throughout the year-long study, tirzepatide provided sustained A1C reduction and progressive weight loss with low occurrence of level two hypoglycemia, an important consideration for people with diabetes and their clinicians."
Based on the efficacy estimand, the 15 mg dose of tirzepatide reduced A1C by 2.37 percent and body weight by 12.9 kg (13.9 percent) in SURPASS-3, and reduced A1C by 2.59 percent and body weight by 10.9 kg (11.6 percent) in SURPASS-5. At this dose, 62.4 percent of participants in SURPASS-5 reached an A1C level of less than 5.7 percent, putting them in the range of those without diabetes. Tirzepatide's overall safety profile is similar to that of the glucagon-like peptide-1 (GLP-1) receptor agonist class, with the most commonly reported adverse events being gastrointestinal side effects that decreased with continued dosing.
"Tirzepatide delivered impressive A1C and body weight reductions in both studies and continued to achieve consistent efficacy and safety results in people living with type 2 diabetes, regardless of how long they have had the condition," commented Mike Mason, president of Lilly Diabetes. "Significantly lowering A1C levels and weight are high priorities throughout the type 2 diabetes treatment journey, and the results we have seen from three SURPASS studies to date fuel our belief in tirzepatide's ability to meet those needs."
Lilly intends to present the full data for SURPASS-3 and SURPASS-5 at the American Diabetes Association's 81st Scientific Sessions as well as in a peer-reviewed publication this year.