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Background: Obesity, a pervasive global health challenge affecting more than 2 billion people, requires comprehensive interventions. Traditional approaches, including lifestyle modification, and diverse drugs targeting a gastrointestinal hormone, including glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (Liraglutide, Semaglutide, Exenatide, Albiglutide, Dulaglutide, Lixisenatide, Orlistat, Phentermine/Topiramate, Lorcaserin, Sibutramine, and Rimonabant) offer tailored strategies; yet their effectiveness is limited and some drugs were taken off the market. Moreover, various surgical modalities, such as Roux-en-Y Bypass surgery, sleeve gastrectomy, intragastric balloons, biliopancreatic diversion with duodenal switch, laparoscopic adjustable gastric band, and vagal nerve blockade can be considered but are associated with numerous side effects and require careful monitoring. Consequently, there is a pressing need for novel anti-obesity treatments.
Methods: This comprehensive review was based on the available data to discuss the traditional pharmaceutical and surgical therapeutical strategies for obesity, going further to discuss tirzepatide's mode of action, its outcomes for obesity, and the associated side effects.
Results: In this landscape, tirzepatide, initially designed for type 2 diabetes management, emerges as a potential game-changer. Functioning as a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, it not only addresses control but also introduces a fresh perspective on weight reduction. This review intricately explores tirzepatide's mechanism, dissecting insights from clinical studies and positioning it as a major force in obesity treatment.
Conclusions: In the middle of significant shifts in obesity management, tirzepatide presents itself as a promising and cost-effective intervention. Its Food and Drug Administration approval marks a milestone in the realm of obesity therapeutics. Going beyond a recapitulation of findings, the conclusion emphasizes the imperative for ongoing exploration and vigilant safety monitoring in tirzepatide's application.
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http://dx.doi.org/10.1016/j.eprac.2024.09.004 | DOI Listing |
Unlabelled: Glucose-dependent insulinotropic peptide receptor (GIPR) stimulates insulin release and regulates metabolic homeostasis. GIPR function is shaped by spatiotemporal trafficking of this G protein-coupled receptor (GPCR). While GPCR endocytosis is traditionally associated with β-arrestin, GIPR internalization is only modestly dependent on this pathway.
View Article and Find Full Text PDFCell Rep Med
August 2025
Department of Endocrinology & Metabolism, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China; The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address:
Postprandial metabolism is a complex and dynamic process involving diverse biomolecules, with islet and gut hormones playing crucial roles. However, how these hormones interact with biomolecules after nutrient intake and coordinate with peripheral insulin resistance (IR) remains elusive. This study characterizes postprandial multi-omics dynamics under mixed meals and four distinct macronutrient loads, investigating hormone secretion patterns, associated responsive molecules, and their relationships with IR.
View Article and Find Full Text PDFJCEM Case Rep
October 2025
Department of Medicine, St. Barnabas Hospital, Bronx, NY 10457, USA.
Tirzepatide (Zepbound), a novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, demonstrates an additive effect, significantly enhancing insulin secretion compared to administering each hormone separately. The case reports presented here, detailing palpitations, musculoskeletal pain, and headaches following tirzepatide administration, raise important questions about the drug's postmarketing safety profile.
View Article and Find Full Text PDFCurr Obes Rep
September 2025
Departament de Bioquímica i Biomedicina Molecular, Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Avda Diagonal 643, Barcelona, Catalonia, 08028, Spain.
Purpose Of The Review: This review summarizes recent evidence highlighting the specific role of adipose tissue in the systemic effects of incretin agonist-based drugs used in the treatment of obesity.
Recent Findings: The development of incretin agonist-based drugs has achieved unprecedented success in the pharmacological treatment of obesity and the improvement of obesity-related comorbidities. While initially shown to significantly reduce adipose tissue through decreased food intake, incretin-based therapy is also increasingly reported to alter the properties of adipose tissue.
Cureus
July 2025
Pharmacy Practice, University of Illinois at Chicago, Rockford, USA.
Purpose To evaluate the impact of incretin-based pharmacotherapy on clinical outcomes in normal to underweight patients with type 2 diabetes mellitus in a real-world setting. Methods Patients with a body mass index less than 25 kg/m prescribed a glucagon-like peptide-1 receptor agonist or glucagon-like peptide-1 receptor agonist/glucose-dependent insulinotropic polypeptide receptor agonist for type 2 diabetes mellitus within a single health system were included in this analysis. The primary objective is a change in hemoglobin A1c from baseline to at least three months after an optimally tolerated incretin-based pharmacotherapeutic agent dose.
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