Efficacy and safety of novel twincretin tirzepatide a dual GIP and GLP-1 receptor agonist in the management of type-2 diabetes: A Cochrane meta-analysis

BACKGROUND: Till date, there is no Cochrane meta-analysis available which has analyzed efficacy and safety of tirzepatide in type-2 diabetes. This meta-analysis was undertaken to address this knowledge gap. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) involving people with diabetes receiving tirzepatide compared to a placebo/active comparator. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in blood–glucose, glycemic targets, weight, lipids, and adverse events. RESULTS: From 34 articles initially screened, data from six RCTs involving 3484 patients were analyzed. Over 12–52 weeks, individuals receiving tirzepatide had significantly greater lowering of HbA1c [mean difference (MD) = -0.75% (95% confidence interval (CI): -1.05 to -0.45); P < 0.01; I(2) = 100%], fasting glucose [MD = -0.75 mmol/L (95% CI: -1.05 to– -0.45); P < 0.01; I(2) = 100%], 2-h post-prandial-glucose [MD = -0.87 mmol/L (95% CI: -1.12 to -0.61); P < 0.01; I(2) = 99%], weight [MD = -8.63 kg (95% CI: -12.89 to -4.36); P < 0.01; I(2) = 100%], body mass index [MD = -1.80 kg/m(2) (95% CI: -2.39 to -1.21); P < 0.01; I(2) = 99%], and waist circumference [MD = -4.43 cm (95% CI: -5.31 to -3.55); P < 0.01; I(2) = 95%] as compared to dulaglutide, semaglutide, degludec, or glargine. Patients receiving tirzepatide had higher odds of achieving HbA1c <6.5% compared to active controls [odds ratio (OR) = 4.39 (95% CI: 2.44–7.92); P < 0.01; I(2) = 90%]. Tirzepatide use had significantly higher odds of weight loss >5% [OR = 19.18 (95% CI: 2.34–157.17); P < 0.01; I(2) = 99%], >10% [OR = 21.40 (95% CI: 2.36–193.94); P < 0.01; I(2) = 98%], and >15% [OR = 32.84 (95% CI: 2.27–474.33); P = 0.01; I(2) = 96%] compared to active-control group. Treatment-emergent adverse events [risk ratio (RR) = 1.43 (95% CI: 1.14–1.80); P < 0.01; I(2) = 40%] and severe adverse events [RR = 1.00 (95% CI: 0.64–1.57); P = 1.00; I(2) = 49%] were not different. High data heterogeneity and the presence of publication bias limits the grading of current data from “moderate to low.” CONCLUSION: Tirzepatide has impressive glycemic efficacy and weight-loss data over 1-year clinical use. The need for higher grade, long-term efficacy, and safety data remains.