Supplementation of tirzepatide for type 2 diabetics on basal insulin improved glycemic control compared to placebo

1. This randomized controlled trial demonstrated that in adult type 2 diabetes patients on daily basal insulin, adding tirzepatide significantly reduced HbA_1C and improved weight loss at 40 weeks compared to placebo.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Basal insulin is used in type 2 diabetic patients with poor glycemic control despite oral hypoglycemics. Increasing the dose of basal insulin can reduce blood glucose levels, however, this also increases the risk of hypoglycemia and weight gain. Glucagon-like peptide-1 (GLP-1) receptor agonists can improve glucose control and weight gain without increasing the risk of hypoglycemia. Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist. The SURPASS-5 randomized, double-blind, placebo-controlled trial investigated whether tirzepatide added to basal insulin improves glycemic control in type 2 diabetes (T2D) patients. Participants with T2D, baseline HbA_1C of 7.0%-10.5%, and on daily basal insulin were randomized to receive a 1:1:1:1 ratio of 5 mg, 10 mg, 15 mg tirzepatide, or placebo between August 30, 2019, and March 20, 2020; participants were followed for 40 weeks and received weekly subcutaneous injections of tirzepatide or placebo. The primary outcome was the mean change from baseline HbA_1C at 40 weeks. Safety outcomes were assessed after 4 weeks. There were significant reductions in HbA_1C at 40 weeks in all treatment groups compared to placebo (5 mg: difference vs. placebo [DVP], -1.24 [95% CI: -1.48 to -1.01], p<0.001. 10 mg: DVP, -1.53 [95% CI: -1.77 to -1.30], p<0.001. 15 mg: DVP, -1.47 [95% CI: -1.71 to -1.23], p<0.001). Additionally, bodyweight was significantly reduced in all three treatment groups compared to placebo (5 mg: DVP, -7.1 kg [95% CI: -8.7 to -5.4], p<0.001. 10 mg: DVP, -9.1 kg [95% CI: -10.7 to -7.5], p<0.001. 15 mg: DVP, -10.5 kg [95% CI: -12.1 to -8.8], p<0.001). Serious adverse events occurred in 7.8%-10.9% of participants in the treatment groups compared to 8.3% of patients in the placebo group. Hypoglycemia occurred in 14.2%-19.3% in the tirzepatide groups versus 12.5% of participants in the placebo cohort. Overall, supplementation of weekly tirzepatide on top of daily basal insulin significantly improved glycemic control and weight loss after 40 weeks in T2D patients. One limitation of this study, however, is that participants in this study were using basal insulin glargine with or without metformin, so these outcomes may not be generalizable to other oral hypoglycemic treatment regimens for T2D.

Click to read the study in JAMA

Click to read an accompanying editorial in JAMA

Relevant Reading: Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial

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