Tirzepatide Improves Glucose Levels from Baseline Irrespective of Gender: A Post Hoc Analysis of the SURPASS-1 to -5 Studies

Tirzepatide is a once-weekly dual GIP and GLP-1 receptor agonist developed as an adjunct to diet and exercise to improve glycaemic control in patients with type 2 diabetes (T2D). The SURPASS (S) program spanning the T2D disease progression from no background therapy to multiple background combinations and comparators led to robust improvements in glycaemic control by tirzepatide as shown by a reduction in HbA1c and fasting serum glucose (FSG) at 40 and/or 52 weeks. This post-hoc analysis from the 5 SURPASS studies (S-1 to S-5) assessed the effect of tirzepatide on glycaemic control and safety, according to patient gender.

Methods:

S-1 to -5 Phase 3 studies were designed to evaluate the efficacy and safety of 3 doses of tirzepatide (5, 10, and 15 mg) in adult patients with T2D. The study population included patients who were newly diagnosed with T2D controlled with diet and exercise only, inadequately controlled on up to 3 oral antihyperglycemic medications (including patients with increased CV risk), or inadequately controlled on basal insulin, with/without metformin. This analysis evaluated the effect of tirzepatide versus placebo, semaglutide (1 mg), insulin degludec, and insulin glargine on HbA1c and FSG improvement from baseline in male and female subgroups. Efficacy was assessed in the modified intention-to-treat (mITT) population while patients were on-treatment and without rescue medication (efficacy estimand).

Results:

Consistent with the primary study results, patients treated with tirzepatide had a greater reduction in HbA1c than placebo or active comparators in both males and females across the S-1 to -5 studies (p < 0.001). In addition, all doses of tirzepatide showed greater reduction in FSG than placebo or active comparators [p < 0.001 (S-1, -2, -3, & -5); 0.027 (S-4)] in males and females (all tests of treatment effects were conducted at a 2-sided alpha level of 0.05, and the confidence interval (CI) calculated at 95%, 2-sided). The most frequently reported adverse events for tirzepatide were GI in nature. They were mild to moderate in severity, transient and usually occurred during the dose escalation period. Severe hypoglycaemia was uncommon with tirzepatide treatment and overall, the risk of hypoglycaemia was comparable to the GLP-1 receptor agonist class.

Discussion/Conclusion:

Across the five SURPASS studies, tirzepatide successfully improved glycaemic control, through significant reduction in HbA1c and FSG from baseline compared to placebo or active comparators, irrespective of patient gender. Additionally, tirzepatide was well tolerated with a similar safety profile to other glucagon-like peptide-1 receptor agonists.