Achievement of HbA1c <6.5% with ≥5% Weight Loss and Without Hypoglycemia in Patients with Type 2 Diabetes Treatment with Tirzepatide: a Post Hoc Analysis of the SURPASS-1 to -5 Studies

Tirzepatide (TZP) is a dual GIP and GLP-1 receptor agonist developed for the treatment of patients with type 2 diabetes (T2D). The SURPASS clinical trials showed that patients treated with TZP had greater HbA1c and bodyweight reductions compared to placebo and active comparator treatments and 66% to 95% of participants treated with TZP achieved a HbA1c ≤6.5% at the end of the trials. Additionally, 54% to 88% of participants treated with TZP achieved a body weight loss of ≥5% at the end of the trial and treatment with TZP was not associated with an increase in hypoglycemia vs comparators. This post hoc analysis evaluated the proportion of participants in the SURPASS-1 to -5 studies achieving a triple composite of HbA1c < 6.5% with ≥5% weight loss and without clinically significant hypoglycemia or severe hypoglycemia.

Methods:

We compared the proportion of participants achieving the triple endpoint between different doses of TZP (5 mg, 10 mg, 15 mg) and respective study active comparators or placebo groups while patients were on treatment and without rescue medication. End of treatment HbA1c and weight were evaluated at week 40 for SURPASS-1, 2 and 5; and week 52 for SURPASS-3 and 4. Hypoglycemia was defined as blood glucose < 54 mg/dL in the presence of symptoms or severe hypoglycemia.

Results:

In all 5 SURPASS studies, significantly more participants treated with any dose of TZP achieved the triple endpoint (p < 0.05) compared to placebo or active comparators. As monotherapy, TZP treatment (5, 10, 15 mg) led to 55%, 64%, 67% of participants achieving the triple endpoint compared to 2% with placebo (SURPASS-1). As add-on to metformin, TZP treatment (5, 10, 15 mg) led to 56%, 71%, 77% achieving the same compared to 44% with semaglutide 1 mg (SURPASS-2). When compared to basal insulin, TZP treatment (5, 10, 15 mg) led to 51%, 70%, 77% achieving the triple endpoint compared to 4% with degludec (SURPASS-3; add-on to metformin) and when added to 1-3 oral antihyperglycemics, TZP treatment (5, 10, 15 mg) led to 44%, 61%, 69% achieving the triple endpoint compared to 3% with glargine U100 (SURPASS-4). Finally, as add-on to basal insulin, TZP treatment (5, 10, 15 mg) led to 39%, 55%, 71% achieving the triple endpoint compared to 3% with placebo (SURPASS-5).

Discussion/Conclusion:

Significantly more participants treated with TZP achieved a HbA1c < 6.5% with ≥5% weight loss and without hypoglycemia compared to placebo, semaglutide 1 mg, or basal insulin. More than 50% of patients achieved this triple endpoint for TZP 10 and 15 mg doses.