Efficacy and safety of tirzepatide, <scp>GLP</scp>‐1 receptor agonists, and other weight loss drugs in overweight and obesity: a network meta‐analysis

Pan, Xin‐Hui; Tan, Bryan; Chin, Yip Han; Lee, Ethan Cheng Zhe; Kong, Gwyneth; Chong, Bryan; Kueh, Martin; Khoo, Chin Meng; Mehta, Anurag; Majety, Priyanka; Grandhi, Gowtham R.; Dimitriadis, Georgios K.; Foo, Roger; Chew, Nicholas W. S.; Le Roux, Carel W.; Mamas, Mamas A.; Chan, Mark Y.

doi:10.1002/oby.24002

Cited by 8 publications

(2 citation statements)

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“…Corresponding to the signal intensity for weight loss poor of GLP-1 RAs in our study, a network meta-analysis showed a decreasing trend in weight loss efficacy for tirzepatide, semaglutide, and liraglutide ( Pan et al, 2024 ). The weight loss effect produced by liraglutide in previous studies was individualized across subjects, with more significant fat mass reductions in females, and the starting point for measurement of the weight loss effect is recommended to start from baseline ( Santini et al, 2023 ; Schultes et al, 2024 ).…”

Section: Discussionsupporting

confidence: 69%

Pharmacovigilance study of GLP-1 receptor agonists for metabolic and nutritional adverse events

He,

Li,

Yang

et al. 2024

Front. Pharmacol.

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Aims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are employed extensively in the management of type 2 diabetes and obesity. However, there is a paucity of real-world data on their safety and tolerability for metabolic and nutritional adverse events in large sample populations. This study aimed to analyse the metabolic and nutritional safety signatures of different GLP-1 RAs by exploring the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).Methods: AEs data were extracted from the FDA Adverse Event Reporting System database for each GLP-1 RA from the time of its launch until the second quarter of 2023. The reported odds ratio (ROR), proportional reporting ratio (PRR), Empirical Bayesian Geometric Mean and Bayesian Confidence Propagation Neural Network were employed to identify AE signals.Results: A system organ class of metabolism and nutrition disorders was employed to filter AE reports, resulting in the identification of 10,450 reports for exenatide, 2,860 reports for liraglutide, 240 reports for albiglutide, 4,847 reports for dulaglutide, 2,905 reports for semaglutide, 1,089 reports for tirzepatide, and 13 reports for lixisenatide. Semaglutide (ROR, 3.34; 95%CI, 3.22), liraglutide (ROR, 2.78; 95%CI, 2.69), and exenatide (ROR, 2.15; 95%CI, 2.11) were associated with metabolism and nutrition disorders. The number of AE signals detected were as follows: albiglutide (n = 1), lixisenatide (n = 2), tirzepatide (n = 11), exenatide (n = 12), liraglutide (n = 16), semaglutide (n = 20), dulaglutide (n = 22). Dehydration was the most frequent AE contributing to serious outcomes for liraglutide (n = 318, 23.93%), dulaglutide (n = 434, 20.90%), semaglutide (n = 370, 25.10%) and tirzepatide (n = 70, 32.86%). The time to onset (TTO) of AE was statistically different between exenatide and the other GLP-1 RAs (p < 0.001), and the Weibull parameters for dehydration for liraglutide, dulaglutide, and semaglutide analyses all showed an early failure-type profile.Conclusion: Our study suggests that exenatide, liraglutide, and semaglutide are more susceptible to metabolic and nutritional AEs than other GLP-1 RAs. Liraglutide, dulaglutide, semaglutide, and tirzepaptide’s potential to induce dehydration, necessitates special attention. Despite certain deficiencies, GLP-1 RAs have considerable potential for the treatment of eating disorders.

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Section: Discussionsupporting

confidence: 69%

Pharmacovigilance study of GLP-1 receptor agonists for metabolic and nutritional adverse events

He,

Li,

Yang

et al. 2024

Front. Pharmacol.

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“…Despite dire forecast trends of metabolic diseases raising concerns of a potential second wave of metabolic-related CVD progression, there is a sense of optimism with the emerging role of novel cardioprotective agents including sodium-glucose cotransporter-2 inhibitors 35 and glucagon-like peptide-1 receptor agonists, 36 that target the reduction of the overall dysmetabolic milieu rather than just CVD in isolation. 37 , 38 Urgent action including research and information exchange is needed to ensure equitable access of lower-income countries to these powerful but expensive medical innovations across Asia.…”

Section: Discussionmentioning

confidence: 99%

The burden of cardiovascular disease in Asia from 2025 to 2050: a forecast analysis for East Asia, South Asia, South-East Asia, Central Asia, and high-income Asia Pacific regions

Goh,

Chong,

Jayabaskaran

et al. 2024

The Lancet Regional Health - Western Pacific

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Response to review by Pan et al.

Holmbäck

2024

Obesity

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TO THE EDITOR: It was with great interest that I read the article titled "Efficacy and safety of tirzepatide, GLP-1 receptor agonists, and other weight loss drugs in overweight and obesity: a network metaanalysis" [1], as new and more effective antiobesity medications have come onto the market since Khera et al. performed their metaanalysis in 2016 [2].In the current meta-analysis by Pan et al., orlistat 120 mg is reported to have both the highest risk for adverse events (AE) and the highest risk for severe adverse events (SAE) compared with the other antiobesity medications included in the meta-analysis, which is quite different from the previous meta-analysis.In that meta-analysis, the Surface Under the Cumulative RAnking curve (SUCRA) for probability of having the fewest AE was around 0.6 for orlistat and around 0.2 for naltrexone-buprion and liraglutide. Also, the odds ratio (OR) for leaving the study due to side effects was lower in orlistat-treated participants (OR: 1.84) compared with liraglutide (OR: 2.95) and naltrexone/bupropion (OR: 2.64).The two orlistat trials included in the current meta-analysis by Pan et al. [1] give no clear indication of severe safety problems. In the included study by Kopelman et al. [3], there were no orlistat-related SAE, which is also seen in Table S2. In the included study by Rössner et al. [4], there was one case of cholelithiasis and one case of diverticulitis during the 2-year study, i.e., two cases in total, which may be seen as fairly low prevalence. Furthermore, it is not clear why there are so few orlistat studies included given the stated inclusion and exclusion criteria (even given the somewhat unclear choice of 1998 as cutoff year). In Table 1, I have listed some studies that I think could have been included. I would greatly appreciate any clarification on this matter.O CONFLICT OF INTEREST STATEMENTUlf Holmbäck has equity interests in Empros Pharma AB and is acting as a consultant for the company, and he holds the patent for the studied weight loss product EMP16, which is a modified release fixeddose combination of orlistat and acarbose.

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Efficacy and safety of tirzepatide, GLP‐1 receptor agonists, and other weight loss drugs in overweight and obesity: a network meta‐analysis

Cited by 8 publications

References 119 publications

Pharmacovigilance study of GLP-1 receptor agonists for metabolic and nutritional adverse events

Pharmacovigilance study of GLP-1 receptor agonists for metabolic and nutritional adverse events

The burden of cardiovascular disease in Asia from 2025 to 2050: a forecast analysis for East Asia, South Asia, South-East Asia, Central Asia, and high-income Asia Pacific regions

Response to review by Pan et al.

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