PERAN ORFORGLIPRON DALAM TATALAKSANA PASIEN DENGAN OBESITAS

THE ROLE OF ORFORGLIPRON IN THE MANAGEMENT OF PATIENTS WITH OBESITY

  • Sugianto Mukmin Perhimpunan Dokter Spesialis Penyakit Dalam Indonesia
  • Amanda Trixie Hardigaloeh Divisi Endokrin Metabolik dan Diabetes, Perhimpunan Dokter Spesialis Penyakit Dalam Indonesia
  • Dira Wahyuni Siregar Fakultas Kedokteran, Institut Kesehatan Helvetia
  • Ermawati MH Siregar Fakultas Kedokteran, Institut Kesehatan Helvetia
  • Agustiawan Fakultas Kedokteran, Institut Kesehatan Helvetia
Keywords: Glucagon-like peptide-1, Kardiometabolik Obesitas, Orforglipron

Abstract

Obesitas merupakan penyakit kronis multifaktorial yang ditandai oleh akumulasi lemak berlebih yang dapat meningkatkan risiko penyakit kardiometabolik. Terapi yang tersedia saat ini masih memiliki keterbatasan, baik dari sisi efektivitas jangka panjang maupun kepatuhan pasien. Orforglipron merupakan agonis reseptor GLP-1 oral non-peptida yang dikembangkan sebagai alternatif terapi obesitas yang lebih praktis. Tinjauan ini bertujuan untuk mengevaluasi peran orforglipron dalam tatalaksana obesitas berdasarkan bukti ilmiah terkini. Metode yang digunakan berupa penelusuran literatur dari uji klinis fase 2 dan fase 3 yang relevan. Hasil penelitian menunjukkan bahwa orforglipron mampu menurunkan berat badan secara signifikan, dengan rerata penurunan sekitar 7,8–12,4% pada studi fase 3 dan hingga 14,7% pada dosis tertinggi studi fase 2. Selain itu, terapi ini juga memperbaiki parameter metabolik seperti kadar glukosa darah, HbA1c, dan lingkar pinggang. Mekanisme kerja orforglipron melibatkan aktivasi reseptor GLP-1 yang meningkatkan sekresi insulin, memperlambat pengosongan lambung, dan menekan nafsu makan. Efek samping yang paling sering dilaporkan berupa gangguan gastrointestinal dan umumnya dapat ditoleransi. Secara klinis, orforglipron menunjukkan potensi sebagai terapi oral yang efektif dan praktis untuk membantu penurunan berat badan pada pasien obesitas maupun overweight dengan komorbid metabolik. Namun, penelitian lanjutan masih diperlukan untuk memastikan keamanan jangka panjang dan posisi optimalnya dalam algoritma terapi obesitas.

References

Ullah MI, Tamanna S. Obesity: clinical impact, pathophysiology, complications, and modern innovations in therapeutic strategies. Medicines. 2025;12(3):19.

Kerr JA, Cini KI, Francis KL, Sawyer SM, Azzopardi PS, Patton GC, et al. Global, regional, and national prevalence of adult overweight and obesity, 1990–2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021. The Lancet. 2025;405(10481):813–38.

Kementerian Kesehatan RI. Survei Kesehatan Indonesia 2023. Jakarta; 2024.

Rochlani Y, Pothineni NV, Kovelamudi S, Mehta JL. Metabolic syndrome: pathophysiology, management, and modulation by natural compounds. Therapeutic Advances in Cardiovascular Disease. 2017;11(8):215.

Elmaleh-Sachs A, Schwartz JL, Bramante CT, Nicklas JM, Gudzune KA, Jay M. Obesity Management in Adults: A Review. JAMA. 2023;330(20):2000–15.

Sukrisman L, Ginanjar E, Nasution SA, Tahapary DL, Habib H, Limantoro C, et al. Konsensus Tatalaksana Multidisiplin Obesitas pada Dewasa. Jakarta: Perkeni; 2025.

American Diabetes Association. 8. Obesity and Weight Management for the Prevention and Treatment of Diabetes: Standards of Care in Diabetes–2026. Diabetes Care. 2026;49(Supplement_1):S166–82.

Pandey RK, Jan M, Mohammad A, Jawaid KA, Naveed M, Abid MA, et al. Efficacy and Safety of Orforglipron in Obese Adults With or Without Diabetes: A Systematic Review and Meta-Analysis. Endocrinology, diabetes & metabolism. 2025;8(6):e70134.

Lütkemeyer C, Pasqualotto E, Ferreira ROM, Chavez MP, Petris IJ, Dos Santos HV, et al. Effects of once-daily oral orforglipron on weight and metabolic markers: a systematic review and meta-analysis of randomized controlled trials. Archives of endocrinology and metabolism. 2024;68:e230469.

Rosenstock J, Robins DA, Duffin KL, Wilson JM, Lin Y, Banerjee H, et al. Orforglipron, an oral non‐peptide glucagon‐like peptide‐1 receptor agonist, improves markers of β‐cell function and insulin sensitivity in type 2 diabetes. Diabetes, Obesity and Metabolism. 2025;27(11):6314–22.

Manoria PC. The Obesity Drug Revolution: New Frontiers in Pharmacotherapy. Cureus. 2025;17(11):e96713.

Gogineni P, Melson E, Papamargaritis D, Davies M. Oral glucagon-like peptide-1 receptor agonists and combinations of entero-pancreatic hormones as treatments for adults with type 2 diabetes: where are we now? Expert opinion on pharmacotherapy. 2024;25(7):801–18.

Tham KW, Abdul Ghani R, Cua SC, Deerochanawong C, Fojas M, Hocking S, et al. Obesity in South and Southeast Asia—A new consensus on care and management. Obesity Reviews. 2023;24(2):e13520.

Safaei M, Sundararajan EA, Driss M, Boulila W, Shapi’i A. A systematic literature review on obesity: Understanding the causes & consequences of obesity and reviewing various machine learning approaches used to predict obesity. Computers in biology and medicine. 2021;136:104754.

Masood B, Moorthy M. Causes of obesity: a review. Clinical Medicine. 2023;23(4):284–91.

Busebee B, Ghusn W, Cifuentes L, Acosta A. Obesity: a review of pathophysiology and classification. In: Mayo Clinic Proceedings. Elsevier. 2023:1842–57.

Kong Y, Yang H, Nie R, Zhang X, Zuo F, Zhang H, et al. Obesity: pathophysiology and therapeutic interventions. Molecular Biomedicine. 2025;6(1):1–41.

Jin X, Qiu T, Li L, Yu R, Chen X, Li C, et al. Pathophysiology of obesity and its associated diseases. Acta Pharmaceutica Sinica B. 2023;13(6):2403–24.

Zheng Z, Zong Y, Ma Y, Tian Y, Pang Y, Zhang C, et al. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Signal Transduction and Targeted Therapy. 2024;9(1):234. https://doi.org/10.1038/s41392-024-01931-z

Lotosky J, Jean X, Altankhuyag A, Khan S, Bernotas A, Sharafshah A, et al. GLP-1 and Its Role in Glycogen Production: A Narrative Review. Biomedicines. 2025;13:1610.

Al-Horani RA, Aliter KF, Aliter HF. Future is Brighter: New Potential Paradigm-Shifting Medications and Regimens for Diabetes and Obesity. Current diabetes reviews. 2024;20(8):84–97.

Holst JJ. The physiology of glucagon-like peptide 1. Physiological reviews. 2007;87(4):1409–39.

Müller TD, Finan B, Bloom SR, D’Alessio D, Drucker DJ, Flatt PR, et al. Glucagon-like peptide 1 (GLP-1). Molecular Metabolism. 2019;30:72–130. https://www.sciencedirect.com/science/article/pii/S2212877819309135

Andersen A, Lund A, Knop FK, Vilsbøll T. Glucagon-like peptide 1 in health and disease. Nature Reviews Endocrinology. 2018;14(7):390–403. https://doi.org/10.1038/s41574-018-0016-2

Sloop KW, Cox AL, Wainscott DB, White A, Droz BA, Stutsman C, et al. The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. Science translational medicine. 2024;16(778):eadp5765.

Rosenstock J, Hsia S, Nevarez Ruiz L, Eyde S, Cox D, Wu W-S, et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes. The New England journal of medicine. 2025;393(11):1065–76.

Kokkorakis M, Chakhtoura M, Rhayem C, Al Rifai J, Ghezzawi M, Valenzuela-Vallejo L, et al. Emerging pharmacotherapies for obesity: A systematic review. Pharmacological reviews. 2025;77(1):100002.

Pillai AA, Sharma AM, Krayem H, Frishman WH, Aronow WS. Orforglipron: A Novel Oral GLP-1 Agonist for the Treatment of Obesity and Diabetes. Cardiology in review. 2025;10:1097

Wharton S, Aronne LJ, Stefanski A, Alfaris NF, Ciudin A, Yokote K, et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. The New England journal of medicine. 2025;393(18):1796–806.

Horn DB, Ryan DH, Kis SG, Alves B, Mu Y, Kim SG, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. Lancet. 2026;406(10522):2927–44.

Published
2026-07-05
How to Cite
Mukmin, S., Hardigaloeh, A. T., Siregar, D. W., Siregar, E. M., & Agustiawan. (2026). PERAN ORFORGLIPRON DALAM TATALAKSANA PASIEN DENGAN OBESITAS: THE ROLE OF ORFORGLIPRON IN THE MANAGEMENT OF PATIENTS WITH OBESITY. Ibnu Sina: Jurnal Kedokteran Dan Kesehatan - Fakultas Kedokteran Universitas Islam Sumatera Utara, 25(2), 561-572. https://doi.org/10.30743/ibnusina.v25i2.1231
Section
Literature Review