New Era in Diabetes and Obesity Treatment - The Effects of GLP-1r, Gipr and GCGR Triagonists

Background: In recent years, the number of people affected by obesity or diabetes has increased dramatically. This growing prevalence resulted in an intensified interest in new methods to fight this problem. More and more drugs have emerged on the pharmaceutical market such as next-generation triagonists targeting glucagon-like peptide-1 (GLP-1R), glucose-dependent insulinotropic polypeptide (GIPR), and glucagon (GCGR) receptors. Aim of the study: This article reviews the information about the effects of GLP-1R, GIPR, GCCR with particular emphasis on it being an obesity treatment, as well as the mechanisms, safety and potential therapeutic effect. Scope of review: The goal of this review was to gather knowledge about the effect of GLP-1R, GIPR and GCGR triagonists in preexperimental and clinical studies. Results: In experimental models triagonists successfully restricted weight gain and prevented hyperglycemia through promoting energy use and thermogenesis via the GCGR component. Triagonist NN1706 has shown to induce dose-dependent weight loss in early stages of clinical trials, however they also triggered specific adverse effects such as second degree atrioventricular blocks. In contrast, Retratrutide has shown an unprecedented clinical efficacy in phase 2 trials. After 48 weekends of a 12 mg dosage there was a 24.2% mean body weight reduction, a result comparable to bariatric surgery. Moreover 72% of prediabetic patients reverted to normoglycemia. Across all cohorts the most common adverse effects were gastrointestinal symptoms and temporary heart rate elevations. Conclusion: GLP-1R/GIPR/GCGR triagonists represent a significant shift in obesity and type 2 diabetes mellitus (T2DM) management. Their effect extend beyond simple appetite suppression to accelerate Their synergism extends beyond simple appetite inhibition for example to increase lipid metabolism, reduce fatty liver disease and accelerate energy expenditure. Clinical implementation will depend on confirming long-term safety in patients ongoing the stage 3 trials. Further research is crucial to ensure the safety of this therapeutic option and confirm these findings.