Tirzepatide outcompetes long-acting insulin in managing type 2 diabetes: a meta-analysis of three phase 3 randomized controlled trials.

In this systematic review and meta-analysis, we compared the efficacy and safety of tirzepatide with those of long-acting or ultra-long-acting insulin for type 2 diabetes. PubMed, Web of Science, Scopus, and Google Scholar were searched from the inception to August 20, 2023. All clinical trials or randomized clinical trials comparing the efficacy of tirzepatide with long-acting or ultra-long-acting insulin for treating type 2 diabetes were included. Three randomized clinical trials, namely SURPASS-3, SURPASS-4, and SURPASS-AP-Combo, with 4339 patients were included. Compared with daily insulin glargine and degludec, once-weekly tirzepatide significantly decreased HbA1c (WMD -1.08%, 95% CI (-1.37, -0.78)), 2h-posprandial blood sugar (BS) (WMD -28.19 mg/dL, 95% CI (-44.98, -11.41)), pre-meal BS (WMD -11.86 mg/dL, 95% CI (-22.83, -0.9)), body weight (WMD -10.61 kg, 95% CI (-13.24, -7.97)), systolic blood pressure (WMD -6.47 mmHg, 95% CI (-8.32, -4.61)), diastolic blood pressure (WMD -2.30 mmHg, 95% CI (-3.05, -1.55)), total cholesterol (WMD -4.78%, 95% CI (-7.05, -2.50)), triglyceride (WMD -14.49%, 95% CI (-19.55, -9.43)), LDL cholesterol (WMD -5.98%, 95% CI (-9.83, -2.13)), and VLDL cholesterol (WMD -14.18%, 95% CI (-19.03, -9.33)) and increased HDL cholesterol (WMD 7.13%, 95% CI (-9.83, -2.13)), with a lower risk of hypoglycemia defined as BS ≤ 70 mg/dL (RR 0.46, 95% CI (0.28, 0.75)). All doses of once-weekly tirzepatide (5 mg, 10 mg, and 15 mg) were superior or non-inferior to insulin. Once-weekly tirzepatide can be a substitution for long-acting insulin in type 2 diabetes with a greater efficacy.