Once-Weekly Tirzepatide Versus Once-Daily Basal Insulin in Managing Type 2 Diabetes Inadequately Controlled With Oral anti-Hyperglycemic Drugs: A Systematic Review and Meta-Analysis

Objective: No meta-analysis has been published comparing the efficacy and safety of tirzepatide vs once-daily basal insulins in subjects with type 2 diabetes (T2D) inadequately controlled with oral anti-hyperglycemic drugs. This meta-analysis was conducted to address this knowledge gap.

Methods: Randomized controlled trials involving subjects with T2D inadequately controlled with oral anti-hyperglycemic drugs and receiving tirzepatide in intervention arm and basal insulins in control arm as add-on therapy were searched throughout the electronic databases. The primary outcome assessed was the change from baseline in hemoglobin A1c (HbA1c).

Results: Three randomized controlled trials involving 4339 subjects met the inclusion criteria. Compared to basal insulins, tirzepatide arms achieved greater reductions from the baseline in HbA1c (tirzepatide 5 mg: mean difference (MD) -0.89% [95% CI: -1.23, -0.54]; tirzepatide 10 mg: MD -1.11% [95% CI: -1.42, -0.79]; and tirzepatide 15 mg: MD -1.23% [95% CI: -1.48, -0.97]; P < .00001 for all). Additionally, the proportions of patients achieving HbA1c levels below 7.0%, 6.5%, and 5.7% were significantly greater in the tirzepatide groups than in the basal insulin group. Greater body weight and blood pressure reductions were observed with tirzepatide than with basal insulins. Moreover, tirzepatide had a more favorable impact on lipid profile. Hypoglycemia was less frequent with tirzepatide. Gastrointestinal adverse events (AEs) were more frequent with tirzepatide (all doses) than basal insulin, although serious AEs were comparable between the 2 groups.

Conclusion: Tirzepatide outperformed basal insulins in controlling blood glucose, body weight, blood pressure, and lipids in subjects with T2D and is generally well-tolerated except for its higher gastrointestinal AEs.