GLP-1 Agonists Do Not Increase Basal Insulin Discontinuation in Type 2 Diabetes: Study
USA: A new target trial emulation published in the Annals of Internal Medicine has found that adding a glucagon-like peptide-1 receptor agonist (GLP-1RA) to basal insulin therapy does not increase the likelihood of discontinuing insulin compared with sodium-glucose cotransporter-2 inhibitors (SGLT-2is) or dipeptidyl peptidase-4 inhibitors (DPP-4is) in patients with type 2 diabetes.
The study was led by Kasia J. Lipska from the Section of Endocrinology, Department of Internal Medicine, Yale School of Medicine, and the Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center, along with colleagues.
GLP-1 receptor agonists are known to reduce insulin requirements when used alongside basal insulin and have become increasingly popular because of their glucose-lowering and weight-loss benefits. However, it has remained uncertain whether initiating these agents allows patients to discontinue basal insulin altogether. To address this question, the investigators compared insulin discontinuation rates among patients initiating GLP-1RAs, SGLT-2 inhibitors, or DPP-4 inhibitors.
The researchers conducted a target trial emulation using electronic health record data from the U.S. Veterans Health Administration. The study included veterans with type 2 diabetes receiving basal insulin who initiated one of the three medication classes between 2020 and 2022. Insulin discontinuation was defined as the first gap of at least 12 months in insulin prescription refills during three years of follow-up.
The analysis included 8,869 matched sets of patients initiating each treatment strategy. Most participants were 65 years or older (63%), male (93%), and White (70%), while nearly half had poorly controlled diabetes with an HbA1c of 9% or higher at baseline.
Key findings from the study include:
- Over three years, 16.7% of patients initiating GLP-1RAs discontinued basal insulin therapy.
- Insulin discontinuation occurred in 17.9% of patients receiving SGLT-2 inhibitors and 17.1% of those receiving DPP-4 inhibitors.
- GLP-1 receptor agonists did not significantly improve the likelihood of insulin discontinuation compared with either SGLT-2 inhibitors or DPP-4 inhibitors.
- Similar findings were observed in the modified per-protocol analysis.
- Subgroup analyses did not identify any patient population in which GLP-1 receptor agonists offered a clear advantage over the oral glucose-lowering agents in facilitating insulin discontinuation.
The authors acknowledged several limitations, including the possibility of residual confounding and potential misclassification of medication exposure and insulin discontinuation when using electronic health record data. These factors may have reduced the ability to detect small differences between treatment groups.
The researchers concluded that among veterans with type 2 diabetes receiving basal insulin, initiating a GLP-1 receptor agonist was not associated with a greater likelihood of discontinuing insulin therapy than initiating an SGLT-2 inhibitor or a DPP-4 inhibitor. The findings suggest that although GLP-1RAs provide several established metabolic benefits, clinicians should not expect these agents to improve insulin discontinuation rates compared with other commonly prescribed glucose-lowering therapies.
Reference: https://doi.org/10.7326/ANNALS-25-05216
Next Story