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); < 0.01; = 100%], fasting glucose [MD = -0.75 mmol/L (95% CI: -1.05 to- -0.45); < 0.01; = 100%], 2-h post-prandial-glucose [MD = -0.87 mmol/L (95% CI: -1.12 to -0.61); < 0.01; = 99%], weight [MD = -8.63 kg (95% CI: -12.89 to -4.36); < 0.01; = 100%], body mass index [MD = -1.80 kg/m (95% CI: -2.39 to -1.21); < 0.01; = 99%], and waist circumference [MD = -4.43 cm (95% CI: -5.31 to -3.55); < 0.01; = 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); < 0.01; = 90%]. Tirzepatide use had significantly higher odds of weight loss >5% [OR = 19.18 (95% CI: 2.34-157.17); < 0.01; = 99%], >10% [OR = 21.40 (95% CI: 2.36-193.94); < 0.01; = 98%], and >15% [OR = 32.84 (95% CI: 2.27-474.33); = 0.01; = 96%] compared to active-control group. Treatment-emergent adverse events [risk ratio (RR) = 1.43 (95% CI: 1.14-1.80); < 0.01; = 40%] and severe adverse events [RR = 1.00 (95% CI: 0.64-1.57); = 1.00; = 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.