Efficacy and Safety of Twincretin Survodutide, a Dual Glucagon-Like Peptide-1 and Glucagon Receptor Agonist as an Anti-Obesity and Anti-Diabetes Medication: A Systematic Review and Meta-Analysis.

Survodutide is a twincretin having dual glucagon-like peptide-1 and glucagon receptor agonist activity, conceptually based on endogenous peptide oxyntomodulin. This systematic review and meta-analysis (SRM) holistically analyzed the body weight lowering, glycemic efficacy, and safety of survodutide. Electronic databases were searched for RCTs involving diabetes and/or obesity patients receiving once-weekly subcutaneous survodutide in intervention arm and placebo/active comparator in control arm. Co-primary outcomes were the percent changes in body weight and HbA1c. Secondary outcomes were to evaluate absolute changes in absolute weight, blood pressure, fatty-liver disease parameters, and adverse events (AEs). Data from 3 RCTs (1088 patients) having follow-up duration ranging from 4-11 months were analyzed. Survodutide at 2.4 mg [MD (mean difference) -7.79% (95% confidence interval [CI]: -11.54, -4.07); I2 = 98%; P < 0.01] and 3.6 mg [MD - 9.08% (95% CI: -11.63, -6.54); I2 = 96%; P < 0.001] was associated with significantly greater percent reductions in body weight compared to placebo. The corresponding absolute body-weight reduction with survodutide 2.4 mg and 3.6 mg was - 9.14 kg (95% CI: -13.76, -4.53) and - 10.23 kg (95% CI: -15.43, -5.04), respectively. Survodutide of 2.4 mg was associated with significant HbA1c reduction [MD: -0.88% (95% CI - 1.72, -0.05); I2 = 99%; P = 0.040]. Survodutide of 2.4 mg [odds ratio (OR): 2.93 (95% CI: 1.66, 5.18); I2 = 0%; P < 0.001] and 3.6 mg [OR: 4.61 (95% CI: 2.33, 9.12); I2 = 0%; P < 0.001] was associated with significantly higher treatment-emergent AEs, compared to placebo, although severe AEs were not increased. Gastrointestinal AEs were the predominant AEs and were dose dependent. Treatment discontinuation due to AEs was significantly higher with survodutide and was dose dependent. Survodutide demonstrates impressive weight and glucose-lowering properties over short-term clinical use. The optimal dose for clinical use ranges from 2.4 to 4.8 mg/week.