Issue

Vol. 3 No. 1 (2026)

Date Log

Submitted
July 10, 2026
Published
July 10, 2026

Copyright (c) 2026 Rasha Salem Salama Alrehaili

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Factors Influencing Adherence to GLP-1 Receptor Agonist Therapy Among Patients Receiving Weight-Loss Injections

https://doi.org/10.64483/202631737
Rasha Salem Salama Alrehaili
Imam Abdulrahman Al Faisal Hospital – Riyadh , Ministry of Health, Saudi Arabia

Corresponding Author(s) : Rasha Salem Salama Alrehaili

Rasalrehaili@moh.gov.sa

Saudi Journal of Medicine and Public Health, Vol. 3 No. 1 (2026)

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized the management of obesity and type 2 diabetes mellitus, with clinical trials demonstrating weight reductions exceeding 15% and significant cardiovascular benefits. However, a substantial and persistent gap exists between the efficacy observed in randomized controlled trials and the real-world effectiveness of these therapies, primarily driven by poor patient adherence and high discontinuation rates. This review synthesizes current evidence on the multifactorial determinants of GLP-1 RA adherence among patients using these medications for weight loss. Drawing upon real-world data from North America, Europe, Latin America, and Asia, we examine the physiological, psychological, economic, and healthcare system-related barriers that undermine treatment persistence. Gastrointestinal adverse effects, particularly nausea and vomiting, represent the most frequently cited physiological barrier, with discontinuation rates peaking during dose escalation. Economic barriers, including high out-of-pocket costs and inconsistent insurance coverage, profoundly impact adherence, with persistence falling below 10% in unsubsidized settings. Psychological factors, including the transient suppression of appetitive drive and the resurgence of "food noise" upon missed doses, further complicate long-term adherence. Healthcare system factors, including the quality of patient-provider communication, the provision of comprehensive education about dose titration and expected outcomes, and the availability of integrated nutritional and behavioral support, emerge as critical modifiable determinants of treatment persistence. This review proposes an integrated care framework incorporating medical nutrition therapy, structured lifestyle support, and patient-centered communication strategies to bridge the efficacy-effectiveness gap and optimize clinical outcomes in patients receiving GLP-1 RA therapy for weight management.

Keywords

GLP-1 receptor agonists; treatment adherence; medication persistence; obesity management; weight-loss injections; gastrointestinal tolerability; healthcare costs; patient education
Alrehaili, R. S. S. (2026). Factors Influencing Adherence to GLP-1 Receptor Agonist Therapy Among Patients Receiving Weight-Loss Injections. Saudi Journal of Medicine and Public Health, 3(1), 50–59. https://doi.org/10.64483/202631737
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. [1] Son JW, le Roux CW, Blüher M, Nauck MA, Lim S. Novel GLP-1-Based Medications for Type 2 Diabetes and Obesity. Endocr Rev. 2026;47(2):159-177.
  2. [2] Harris MI. Medical care for patients with diabetes: epidemiologic aspects. Ann Intern Med. 1996;124(1 Pt 2):117-122.
  3. [3] Alfaris N, Waldrop S, Johnson V, Boaventura B, Kendrick K, Stanford FC. GLP-1 Single, Dual, and Triple Receptor Agonists for Treating Type 2 Diabetes and Obesity: A Narrative Review. eClinicalMedicine. 2024;75:102782.
  4. [4] Aronne LJ, Horn DB, Le Roux CW, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025;393(1):26-36.
  5. [5] Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221-2232.
  6. [6] American Diabetes Association. Summary of Revisions: Standards of Medical Care in Diabetes—2020. Diabetes Care. 2020;43(Suppl 1):S4-S6.
  7. [7] Thomsen RW, Mailhac A, Lohde JB, Pottégard A. Real-World Evidence on the Utilization, Clinical and Comparative Effectiveness, and Adverse Effects of Newer GLP-1RA-Based Weight-Loss Therapies. Diabetes Obes Metab. 2025;27(Suppl 1):66-88.
  8. [8] Rodriguez PJ, Zhang V, Gratzl S, et al. Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity. JAMA Netw Open. 2025;8(1):e2457349.
  9. [9] Gleason PP, Urick BY, Marshall LZ, Friedlander N, Qiu Y, Leslie RS. Real-World Persistence and Adherence to Glucagon-like Peptide-1 Receptor Agonists among Obese Commercially Insured Adults without Diabetes. J Manag Care Spec Pharm. 2024;30(8):860-867.
  10. [10] Sarpatwari A, Soto MJ, Ganguli L, Sloan CE, Goss F, Sinaiko AD. Glucagon-Like Peptide-1 Receptor Agonist Order Fills and Out-of-Pocket Costs by Race, Ethnicity, and Indication. JAMA Health Forum. 2025;6(6):e254258.
  11. [11] Dziewierz A, Siudak Z. Adherence and Persistence with GLP-1-Based Therapies: International Real-World Evidence and the Role of Nutritional and Lifestyle Support—A Narrative Review. Nutrients. 2026;18(11):1761.
  12. [12] Lin J, Lingohr-Smith M, Fan T. Real-World Medication Persistence and Outcomes Associated with Basal Insulin and Glucagon-Like Peptide 1 Receptor Agonist Free-Dose Combination Therapy in Patients with Type 2 Diabetes in the US. Clinicoecon Outcomes Res. 2016;9:19-29.
  13. [13] Polonsky W, Gamble C, Iyer N, Martin M, Hamersky C. Exploring Why People With Type 2 Diabetes Do or Do Not Persist With Glucagon-Like Peptide-1 Receptor Agonist Therapy: A Qualitative Study. Diabetes Spectr. 2023;36(1):73-81.
  14. [14] World Health Organization. Adherence to Long-Term Therapies: Evidence for Action. Geneva: WHO; 2003.
  15. [15] Cramer JA, Roy A, Burrell A, et al. Medication Compliance and Persistence: Terminology and Definitions. Value Health. 2008;11(1):44-47.
  16. [16] Clifford S, Perez-Nieves M, Skalicky AM, Reaney M, Coyne KS. A Systematic Literature Review of Methodologies Used to Assess Medication Adherence in Patients with Diabetes. Curr Med Res Opin. 2014;30(6):1071-1085.
  17. [17] Giorgino F, Penfornis A, Pechtner V, Gentilella R, Corcos A. Adherence to Antihyperglycemic Medications and Glucagon-Like Peptide 1-Receptor Agonists in Type 2 Diabetes: Clinical Consequences and Strategies for Improvement. Patient Prefer Adherence. 2018;12:707-719.
  18. [18] Lim CE, Pasternak B, Eliasson B, Ueda P. Treatment Discontinuation among Users of GLP-1 Receptor Agonists and SGLT2 Inhibitors in a National Population of Individuals with Type 2 Diabetes. Diabetologia. 2025;68(8):1680-1695.
  19. [19] Lassen MCH, Johansen ND, Modin D, et al. Adherence to Glucagon-Like Peptide-1 Receptor Agonist Treatment in Type 2 Diabetes Mellitus: A Nationwide Registry Study. Diabetes Obes Metab. 2024;26(11):5239-5250.
  20. [20] Siudak Z, Daniec M, Szarpak L, Tomaszewska M, Kozela M, Dziewierz A. Low Long-Term Persistence with GLP-1 Receptor Agonists Treatment: Real-World Evidence from a Large Polish Cohort. Diabetes Obes Metab. 2025;27(12):6011-6017.
  21. [21] Machado-Duque ME, Gaviria-Mendoza A, Valladares-Restrepo LF, Machado-Alba JE. Persistence of Weekly Injectable Semaglutide Use in Patients with Diabetes Mellitus and Obesity: A Retrospective Follow-Up in Colombia. Drugs Real World Outcomes. 2025;12(4):615-622.
  22. [22] Ali M, Amirthalingam P, Alshareef H, et al. Medication Adherence to Semaglutide versus Empagliflozin in Adults with Type 2 Diabetes: A Retrospective Observational Study in Saudi Arabia. Patient Prefer Adherence. 2025;19:4179-4190.
  23. [23] Kadowaki T, Heftdal LD, Ko HJ, et al. Oral Semaglutide in an East Asian Population With Overweight or Obesity, With or Without Type 2 Diabetes: The OASIS 2 Randomized Clinical Trial. JAMA Intern Med. 2025;185(11):1206-1217.
  24. [24] Ismaiel A, Scarlata GGM, Boitos I, et al. Gastrointestinal Adverse Events Associated with GLP-1 RA in Non-Diabetic Patients with Overweight or Obesity: A Systematic Review and Network Meta-Analysis. Int J Obes. 2025;49(12):1946-1957.
  25. [25] Müller TD, Finan B, Bloom SR, et al. Glucagon-Like Peptide 1 (GLP-1). Mol Metab. 2019;30:72-130.
  26. [26] Sikirica MV, Martin AA, Wood R, Leith A, Piercy J, Higgins V. Reasons for Discontinuation of GLP1 Receptor Agonists: Data from a Real-World Cross-Sectional Survey of Physicians and Their Patients with Type 2 Diabetes. Diabetes Metab Syndr Obes. 2017;10:403-412.
  27. [27] Factors Contributing to Non-Persistence of Glucagon-Like Peptide-1 Agonists: A Cross-Sectional Study. Available at: ScienceDirect. 2025.
  28. [28] Wharton S, Freitas P, Hjelmesæth J, et al. Once-Weekly Semaglutide 7·2 Mg in Adults with Obesity (STEP UP): A Randomised, Controlled, Phase 3b Trial. Lancet Diabetes Endocrinol. 2025;13(12):949-963.
  29. [29] Steinert RE, Schirra J, Meyer-Gerspach AC, et al. Effect of Glucagon-Like Peptide-1 Receptor Antagonism on Appetite and Food Intake in Healthy Men. Am J Clin Nutr. 2014;100(2):514-523.
  30. [30] Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional Priorities to Support GLP-1 Therapy for Obesity: A Joint Advisory From the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and the Obesity Society. Am J Lifestyle Med. 2025;19(2):344-367.
  31. [31] Jensen SBK, Sorensen V, Sandsdal RM, et al. Bone Health After Exercise Alone, GLP-1 Receptor Agonist Treatment, or Combination Treatment: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024;7(6):e2416775.
  32. [32] Cava E, Yeat NC, Mittendorfer B. Preserving Healthy Muscle during Weight Loss. Adv Nutr. 2017;8(3):511-519.
  33. [33] Bauer J, Biolo G, Cederholm T, et al. Evidence-Based Recommendations for Optimal Dietary Protein Intake in Older People: A Position Paper from the PROT-AGE Study Group. J Am Med Dir Assoc. 2013;14(8):542-559.
  34. [34] Deutz NEP, Bauer JM, Barazzoni R, et al. Protein Intake and Exercise for Optimal Muscle Function with Aging: Recommendations from the ESPEN Expert Group. Clin Nutr. 2014;33(6):929-936.
  35. [35] Hayashi D, Edwards C, Emond JA, et al. What Is Food Noise? A Conceptual Model of Food Cue Reactivity. Nutrients. 2023;15(22):4809.
  36. [36] Richard JE, Anderberg RH, Goteson A, Gribble FM, Reimann F, Skibicka KP. Activation of the GLP-1 Receptors in the Nucleus of the Solitary Tract Reduces Food Reward Behavior and Targets the Mesolimbic System. PLoS One. 2015;10(3):e0119034.
  37. [37] Choi W, Nho YH, Qiu L, et al. Brain Activity Associated with Breakthrough Food Preoccupation in an Individual on Tirzepatide. Nat Med. 2025;31(12):4038-4043.
  38. [38] Dang V, Sambuco N, Yammine L, Versace F. Do GLP-1 Receptor Agonists Alter Brain Responses to Reward-Related Cues? A Systematic Review. bioRxiv. 2026.
  39. [39] Berg S, Stickle H, Rose SJ, Nemec EC. Discontinuing Glucagon-Like Peptide-1 Receptor Agonists and Body Habitus: A Systematic Review and Meta-Analysis. Obes Rev. 2025;26(4):e13929.
  40. [40] Kolli RT, Aoutla S, Jyothi N, Mohamed Kalifa MRH, Raju A, Cheenikkal Muralidharan K. Rebound or Retention: A Meta-Analysis of Weight Regain After the Discontinuation of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Other Anti-Obesity Drugs. Cureus. 2025;17(2):e94926.
  41. [41] Polonsky WH, Skinner TC. Perceived Treatment Efficacy: An Overlooked Opportunity in Diabetes Care. Clin Diabetes. 2010;28(2):89-92.
  42. [42] Foot H, La Caze A, Gujral G, Cottrell N. The Necessity-Concerns Framework Predicts Adherence to Medication in Multiple Illness Conditions: A Meta-Analysis. Patient Educ Couns. 2016;99(5):706-717.
  43. [43] Levi J, Wang J, Venter F, Hill A. Estimated Minimum Prices and Lowest Available National Prices for Antiobesity Medications: Improving Affordability and Access to Treatment. Obesity. 2023;31(5):1270-1279.
  44. [44] Hwang JH, Laiteerapong N, Huang ES, Kim DD. Lifetime Health Effects and Cost-Effectiveness of Tirzepatide and Semaglutide in US Adults. JAMA Health Forum. 2025;6(1):e245586.
  45. [45] Zhang D, Gencerliler N, Mukhopadhyay A, et al. Association of Patient Cost Sharing With Adherence to GLP-1RA and Adverse Health Outcomes. Diabetes Care. 2025;48(8):1329-1336.
  46. [46] IQVIA. Patient Behavior: How Does Price Sensitivity and Adherence Shape the GLP-1 Market. IQVIA Blog. November 19, 2025.
  47. [47] Khan T, Tsipas S, Loustalot F, et al. State-Level Variation in Glucagon-Like Peptide-1 Receptor Agonists Fills and Spending by Obesity Prevalence, 2023. J Am Heart Assoc. 2025;14(12):e043137.
  48. [48] Rowland S, Hummel S, Sikand G, Brandt EJ. Expansion of Medicare Coverage for Medical Nutrition Therapy. JAMA Netw Open. 2025;8(7):e257716.
  49. [49] Wu J, Perez A, Sullivan PW. Patterns and Costs Associated with Glucagon-Like Peptide-1 Receptor Agonist Use in US Adults with Type 2 Diabetes. J Manag Care Spec Pharm. 2025;31(10):1029-1038.
  50. [50] National Institute for Health and Care Excellence. Semaglutide for Managing Overweight and Obesity. London: NICE; 2023. (Technology Appraisal TA875).
  51. [51] Malmenas M, Bouchard JR, Langer J. Retrospective Real-World Adherence in Patients with Type 2 Diabetes Initiating Once-Daily Liraglutide 1.8 mg or Twice-Daily Exenatide 10 μg. Clin Ther. 2013;35(6):795-807.
  52. [52] Johnston SS, Nguyen H, Felber E, et al. Retrospective Study of Adherence to Glucagon-Like Peptide-1 Receptor Agonist Therapy in Patients with Type 2 Diabetes Mellitus in the United States. Adv Ther. 2014;31(11):1119-1133.
  53. [53] Alatorre C, Fernandez Landó L, Yu M, et al. Treatment Patterns in Patients with Type 2 Diabetes Mellitus Treated with Glucagon-Like Peptide-1 Receptor Agonists: Higher Adherence and Persistence with Dulaglutide Compared with Once-Weekly Exenatide and Liraglutide. Diabetes Obes Metab. 2017;19(7):953-961.
  54. [54] Matfin G, van Brunt K, Zimmermann AG, Threlkeld R, Ignaut DA. Safe and Effective Use of the Once Weekly Dulaglutide Single-Dose Pen in Injection-Naive Patients with Type 2 Diabetes. J Diabetes Sci Technol. 2015;9(5):1071-1079.
  55. [55] Palanca A, Ampudia-Blasco FJ, Calderón JM, et al. Real-World Evaluation of GLP-1 Receptor Agonist Therapy Persistence, Adherence and Therapeutic Inertia Among Obese Adults with Type 2 Diabetes. Diabetes Ther. 2023;14(4):719-734.
  56. [56] Sikand G, Cole RE, Handu D, et al. Clinical and Cost Benefits of Medical Nutrition Therapy by Registered Dietitian Nutritionists for Management of Dyslipidemia: A Systematic Review and Meta-Analysis. J Clin Lipidol. 2018;12(5):1113-1122.
  57. [57] Diabetes Prevention Program Research Group. 10-Year Follow-up of Diabetes Incidence and Weight Loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374(9702):1677-1686.
  58. [58] Omada Health, Inc. Omada Health's Enhanced GLP-1 Care Track Demonstrates Increased Medication Persistence and Weight Loss Outcomes at 12 and 24 Weeks. Company-Published Real-World Analysis. June 17, 2025.
  59. [59] Mathioudakis N, Lalani B, Abusamaan MS, et al. An AI-Powered Lifestyle Intervention vs Human Coaching in the Diabetes Prevention Program: A Randomized Clinical Trial. JAMA. 2025;334(24):2079-2089.
  60. [60] Deanfield J, Lincoff AM, Kahn SE, et al. Semaglutide and Cardiovascular Outcomes by Baseline and Changes in Adiposity Measurements: A Prespecified Analysis of the SELECT Trial. Lancet. 2025;406(10470):2257-2268.
  61. [61] Pérez-Belmonte LM, Prieto-Lain N, Gómez-Huelgas R. Therapeutic Strategies for Diabetic Cardiomyopathy: SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Beyond. Kardiol Pol. 2025;83(7-8):795-797.
  62. [62] Kalayci A, Januzzi JL, Mitsunami M, Tanboga IH, Karabay CY, Gibson CM. Clinical Features Modifying the Cardiovascular Benefits of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis. Eur Heart J Cardiovasc Pharmacother. 2025;11(5):552-561.
  63. [63] Kansakar U, Jankauskas SS, Pande S, Mone P, Varzideh F, Santulli G. Orforglipron: A Comprehensive Review of an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity and Type 2 Diabetes. Int J Mol Sci. 2026;27(3):1409.
  64. [64] Celletti F, Farrar J, De Regil L. World Health Organization Guideline on the Use and Indications of Glucagon-Like Peptide-1 Therapies for the Treatment of Obesity in Adults. JAMA. 2026;335(5):434-438.
  65. [65] Von Haehling S, Sato R, Langer H, et al. Muscle Loss in Obesity Therapy as a Therapeutic Target: Trial Design and Endpoints for Regulatory Discussions. J Cachexia Sarcopenia Muscle. 2025;16(2):e70147.
Read More
Author biographies is not available.
Download
PDF
Statistic
Read Counter : 0 Download : 0