Research reveals that combining GLP-1 receptor agonists with basal insulin does not significantly increase the likelihood of insulin discontinuation in adults with type 2 diabetes, challenging assumptions about their role in insulin dependency reduction.
Adding a GLP-1 drug to basal insulin may not make it any easier for people with type 2 diabetes to stop using insulin altogether, according to research published in Annals of Internal Medicine. In a large real-world analysis of veterans, the chance of discontinuing basal insulin over 3 years was broadly similar whether patients were taking a GLP-1 receptor agonist, an SGLT2 inhibitor or a DPP-4 inhibitor alongside insulin.
The study used electronic health records from the Veterans Health Administration Corporate Data Warehouse and applied a target-trial emulation design, which is intended to mirror the structure of a randomised trial using observational data. After propensity score matching, the researchers formed 8,869 matched sets of adults with type 2 diabetes who were using basal insulin and starting one of the three drug classes between 2020 and 2022. Most of the GLP-1 group received semaglutide, while empagliflozin dominated the SGLT2 group and alogliptin was the main DPP-4 inhibitor used.
At 3 years, insulin had been stopped by 16.7% of those on GLP-1 therapy, 17.9% of those taking an SGLT2 inhibitor and 17.1% of those using a DPP-4 inhibitor. The investigators said the results were consistent across additional analyses, including one using a less conservative definition of insulin discontinuation and another that followed patients only while they remained in their original treatment group.
Kasia J. Lipska, an assistant professor of medicine at Yale School of Medicine, said the results suggest GLP-1 drugs should not be viewed solely through the lens of insulin withdrawal. She said treatment choices should instead reflect the broader clinical picture, including cardiovascular and kidney disease, obesity, hypoglycaemia risk, side effects, treatment burden, cost, access and patient preference. Lipska added that GLP-1 medicines remain important, but their value should not be judged only by whether they allow someone to come off insulin completely.
The findings also showed that stopping insulin was more likely in adults younger than 65 and in those starting from a lower daily insulin dose, below 50 units. By contrast, therapy persistence with the accompanying diabetes medicines varied: GLP-1 treatment was discontinued in 12.3% of users, SGLT2 therapy in 13.4% and DPP-4 treatment in 26.1% during follow-up. Lipska said future research should look at ways to improve insulin discontinuation and assess whether tirzepatide and other incretin-based drugs may do more to reduce insulin dependence.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
