GLP-1 Drugs Do Not Increase Insulin Discontinuation Compared With Other Diabetes Medications: Study
USA: A study published in the Annals of Internal Medicine has found that glucagon-like peptide-1 (GLP-1) receptor agonists do not significantly increase insulin discontinuation rates compared with sodium-glucose cotransporter-2 (SGLT2) inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with diabetes.
The study, involving nearly 9,000 patients from the US Department of Veterans Affairs, found that approximately 17% of participants were able to discontinue insulin therapy. The findings suggest that GLP-1 drugs do not provide a significant advantage over other glucose-lowering medications in enabling patients to stop insulin use.
Adding a GLP-1 receptor agonist to basal insulin can reduce insulin requirements in people with type 2 diabetes (T2D), but whether these medications can help patients eventually stop insulin remains uncertain.
Researchers led by Kasia J. Lipska of the Section of Endocrinology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, and the Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center, Veterans Affairs Connecticut Healthcare System, along with colleagues, compared insulin discontinuation among patients starting GLP-1 receptor agonists, SGLT2 inhibitors or DPP-4 inhibitors.
The researchers used a target trial emulation design based on electronic health record data from the U.S. Veterans Health Administration. The analysis included veterans with T2D who were receiving basal insulin and initiated one of the three medication classes between 2020 and 2022.
Insulin discontinuation was defined as having a gap of at least 12 months between insulin prescription fills during three years of follow-up.
Key findings included:
- The analysis included 8,869 matched sets of patients initiating GLP-1 receptor agonists, SGLT2 inhibitors or DPP-4 inhibitors.
- Among GLP-1 receptor agonist users, 16.7% discontinued insulin compared with 17.9% of SGLT2 inhibitor users and 17.1% of DPP-4 inhibitor users.
- GLP-1 receptor agonists were not associated with a significant difference in insulin discontinuation compared with SGLT2 inhibitors or DPP-4 inhibitors.
- The findings remained similar in a modified per-protocol analysis.
- No patient subgroup demonstrated a comparative advantage of GLP-1 receptor agonists for stopping insulin therapy.
Among GLP-1 receptor agonist users, semaglutide accounted for 76.6% of treatments, followed by dulaglutide (15.2%), liraglutide (7.9%), and exenatide (0.3%). The SGLT2 inhibitor group predominantly received empagliflozin (99.7%), while alogliptin accounted for 95.9% of DPP-4 inhibitor use.
The study population was predominantly older and male, with 63% aged 65 years or older and 93% being men. Around 48% had an HbA1c level of at least 9%.
The researchers noted possible residual confounding as a limitation. Misclassification of medication exposure and insulin discontinuation based on electronic health records could also have influenced the observed associations.
Overall, among veterans with T2D receiving basal insulin, adding a GLP-1 receptor agonist did not increase the likelihood of insulin discontinuation compared with initiating an SGLT2 or DPP-4 inhibitor.
Reference:
Lipska KJ, Zawack K, Yan L, Mutalik P, Li J, Gulanski B, Ioannou GN, Aslan M. Comparative Effectiveness of Glucagon-like Peptide-1 Receptor Agonists Versus Oral Agents for Insulin Discontinuation in Type 2 Diabetes: A Target Trial Emulation. Ann Intern Med. 2026 Aug;179(8):1128-1139. doi: 10.7326/ANNALS-25-05216. Epub 2026 Jul 14. PMID: 42441965.
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