Ganakumar V, Fernandez CJ, Pappachan JM. Glucagon-like peptide-1 receptor agonists in type 2 diabetes: Evidence for disease modification and therapeutic switching. World J Diabetes 2026; 17(6): 116477 [DOI: 10.4239/wjd.116477]
Corresponding Author of This Article
Joseph M Pappachan, MD, Professor, Faculty of Science, Manchester Metropolitan University, All Saints Building, Oxford Road, Manchester M15 6BH, Greater Manchester, United Kingdom. drpappachan@yahoo.co.in
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Endocrinology & Metabolism
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editorial
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Ganakumar V, Fernandez CJ, Pappachan JM. Glucagon-like peptide-1 receptor agonists in type 2 diabetes: Evidence for disease modification and therapeutic switching. World J Diabetes 2026; 17(6): 116477 [DOI: 10.4239/wjd.116477]
World J Diabetes. Jun 15, 2026; 17(6): 116477 Published online Jun 15, 2026. doi: 10.4239/wjd.116477
Glucagon-like peptide-1 receptor agonists in type 2 diabetes: Evidence for disease modification and therapeutic switching
Vanishri Ganakumar, Cornelius J Fernandez, Joseph M Pappachan
Vanishri Ganakumar, Department of Endocrinology, Jawaharlal Nehru Medical College, Belagavi 590010, Karnataka, India
Cornelius J Fernandez, Department of Endocrinology and Metabolism, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston PE21 9QS, Lincolnshire, United Kingdom
Joseph M Pappachan, Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, Greater Manchester, United Kingdom
Joseph M Pappachan, Department of Endocrinology and Metabolism, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal 576104, India
Joseph M Pappachan, Department of Endocrinology and Metabolism, Countess of Chester Hospital NHS Trust, Chester CH2 1UL, Cheshire West and Chester, United Kingdom
Co-first authors: Vanishri Ganakumar and Cornelius J Fernandez.
Author contributions: Ganakumar V and Fernandez CJ contributed to the initial drafting of the work by performing the literature search and interpretation of relevant literature and share the first authorship; Fernandez CJ also prepared the figures for the manuscript and contributed substantially in addition to the revision process; Pappachan JM conceptualized the idea and provided overall supervision to the drafting process and figure preparation; all authors contributed to the revision of the article for important intellectual content, and all authors have read and approved the final version of the manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Corresponding author: Joseph M Pappachan, MD, Professor, Faculty of Science, Manchester Metropolitan University, All Saints Building, Oxford Road, Manchester M15 6BH, Greater Manchester, United Kingdom. drpappachan@yahoo.co.in
Received: November 12, 2025 Revised: December 12, 2025 Accepted: January 12, 2026 Published online: June 15, 2026 Processing time: 211 Days and 15.7 Hours
Abstract
The discovery of the incretin system and the subsequent development of pharmacotherapeutic agents to manipulate incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, as well as glucagon, with various drugs, have revolutionised the management of type 2 diabetes mellitus (T2DM) in the 21st century. The first few drug molecules in this group were the GLP-1 receptor agonists (GLP-1RA), which have been used for treating patients with T2DM in the past 2 decades, and newer molecules, including incretin polyagonists, are being added to the growing list of incretin-based drugs in recent years. Generally, these newer molecules possess longer biological half-lives and dosing intervals, better weight loss potentials, higher efficacy in glycemic control and possibly improved disease-modifying properties such as a higher chance for T2DM remission and better cardiometabolic outcomes. Therefore, newer incretin-based medications are currently preferred by many diabetologists and switching from older molecules to the newer ones is not uncommon in day-to-day clinical practice. However, outside the remit of randomised controlled trial settings, there is only limited evidence emerging from real-world data. A study by Kassem et al published in the World Journal of Diabetes provides us with robust evidence from a large real-world study of 18047 patients with T2DM from Israel on the benefits of switching from an old GLP-1RA to a newer agent, with a remarkable improvement in glycemic control. With the most up-to-date evidence, we update the rationale for switching GLP-1RA molecules in managing T2DM with a detailed review of the therapeutic benefits, including the anticipated cardiometabolic outcomes and cost benefit analysis from such switching in this editorial.
Core Tip: Pharmacological manipulation of the incretin system has revolutionised the management of type 2 diabetes mellitus (T2DM) in the 21st century. The first few drug molecules in this group were the glucagon-like peptide-1 receptor agonists (GLP-1RA), which have been used for treating patients with T2DM in the past 2 decades. Newer molecules, including incretin polyagonists, with longer half-lives and dosing intervals, and better cardiometabolic outcomes, are being added recently. A study by Kassem et al published in the World Journal of Diabetes provides us with robust evidence from a large real-world study from Israel on the benefits of switching from an old GLP-1RA to a newer agent, the theme of this editorial.
