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.