FRI067 Efficacy And Safety Of Glucagon-like Peptide 1 Analogs And Agonists (aGLP1) In Overweight/Obese Patients: A Systematic Review And An Updated Network Meta-analysis
Authors: Silva Caroliny Hellen , Mund Eduardo , Watanabe Janine , José Victor , Lorene Yasmin , Lucena Larissa , Lima Josivan G 
Published: October 2023

Disclosure: C.H. Silva: None. E. Mund: None. J. Watanabe: None. V. José: None. Y. Lorene: None. L. Lucena: None. J.G. Lima: None.

Background: Obesity is a chronic disease related to mortality worldwide. aGLP1 are the more effective therapeutic class for weight loss. We aimed to evaluate the efficacy in weight loss and adverse effects using different aGLP1. Methods: PubMed, EMBASE and Cochrane databases were searched for RCTs that investigated aGLP1 in the diabetic population, assessing weight loss, acceptability and safety of treatments. A Bayesian network meta-analysis was conducted to estimate the relative effects between treatments and to rank each one according to the Surface Under the Cumulative Ranking Curve (SUCRA). Results: 71 RCTs with 29105 patients were included. The risk of discontinuation of treatment was significantly high for taspoglutide (4.76; 95% CrI: 1.39, 17.72), exenatide (2.54; 95% CrI: 1.6, 4.21), semaglutide &lt; 2.4 mg (2.31; 95% CrI: 1.49, 3.74), tirzepatide 15 mg (2.27; 95% CrI: 1.2, 4.28), tirzepatide 10 mg (2.2; 95% CrI: 1.1, 4.18), liraglutide ≤ 1.8 mg (2.19; 95% CrI: 1.51, 3.3), liraglutide &gt; 1.8 mg (2.19; 95% CrI: 1.58, 3.07) and semaglutide ≥ 2.4 mg (2.06; 95% CrI: 1.29, 3.28). SUCRA values were higher (i.e., lower risks) for lixisenatide (0.848), tirzepatide 5 mg (0.743) and efpeglenatide (0.676). The following drugs provided significant weight loss: tirzepatide 15 mg (-9.01; 95% CrI: -11.34, -6.84), tirzepatide 10 mg (-7.66; 95% CrI: -10.39, -4.87), semaglutide ≥ 2.4 mg (-7.2; 95% CrI: -9.11, -5.36), tirzepatide 5 mg (-5.63; 95% CrI: -8.44, -2.84), semaglutide &lt; 2.4 mg (-5.07; 95% CrI: -6.9, -3.21), liraglutide &gt; 1.8 mg (-4.77; 95% CrI: -5.94, -3.6), efpeglenatide (-3.49; 95% CrI: -6.39, -0.62), liraglutide ≤ 1.8 mg (-2.53; 95% CrI: -3.52, -1.54), exenatide (-1.71; 95% CrI: -2.98, -0.47). The best treatments according to SUCRA were tirzepatide 15 mg (0.980), tirzepatide 10 mg (0.890) and semaglutide ≥ 2.4 mg (0.864). Also, tirzepatide 15 mg outperformed liraglutide &gt; 1.8 mg (-4.24; 95% CrI: -6.85, -1.85), liraglutide ≤ 1.8 mg (-6.51; 95% CrI: -8.92, -4.2), dulaglutide &lt; 1.5 mg (-8.02; 95% CrI: -10.89, -5.38), dulaglutide ≥ 1.5 mg (-7.48; 95% CrI: -10.52, -4.32), exenatide (-7.31; 95% CrI: -9.91, -4.9), semaglutide &lt; 2.4 mg (-3.98; 95% CrI: -6.67, -1.26), tirzepatide 5 mg (-3.45; 95% CrI: -5.87, -0.93), efpeglenatide (-5.53; 95% CrI: -9.32, -1.86), taspoglutide (-7.78; 95% CrI: -11.79, -3.99) and lixisenatide (-8.3; 95% CrI: -12.34, -4.48). Regarding safety of treatments, the SUCRA values for risk of nausea were higher (i.e., lower risk) for tirzepatide 5 mg (0.809), efpeglenatide (0.671) and dulaglutide ≥ 1.5 mg, while for risk of vomiting the best treatments were dulaglutide &lt; 1.5 mg (0.791), tirzepatide 5 mg (0.742) and liraglutide ≤ 1.8 mg (0.720). Conclusion: Tirzepatide 15 mg appears to be the most effective aGLP1 for weight reduction while it is similar to other aGLP1 regarding acceptability and safety. Taspoglutide was remarkably inferior to other aGLP1 considering discontinuation risk.

Presentation: Friday, June 16, 2023