Research using Veterans Health Administration data reveals that adding GLP-1 receptor agonists to basal insulin does not significantly change the chances of patients stopping insulin, challenging previous assumptions about their role in insulin withdrawal.
A new analysis of veterans with type 2 diabetes suggests that adding a GLP-1 receptor agonist to basal insulin does not make patients more likely to stop insulin than adding other common glucose-lowering drugs, according to research published in Annals of Internal Medicine.
The study used Veterans Health Administration electronic health records in a target trial emulation, a method that tries to mimic a randomised trial using observational data. After matching, researchers compared 8,869 adults who started a GLP-1 drug, an SGLT2 inhibitor or a DPP-4 inhibitor while already using basal insulin. Over 3 years, insulin was discontinued in 16.7% of GLP-1 users, 17.9% of SGLT2 inhibitor users and 17.1% of DPP-4 inhibitor users, a pattern the investigators said pointed to broadly similar odds across the three drug classes.
The findings may temper expectations that GLP-1 therapy will often allow patients to come off insulin altogether. In comments to Healio, Kasia J. Lipska, an assistant professor of medicine at Yale School of Medicine, said clinicians should judge these medicines by the full clinical picture, including cardiovascular and kidney disease, obesity, hypoglycaemia risk, side effects, treatment burden, cost, access and patient preference. She said GLP-1 drugs remain valuable, but their worth should not be measured only by whether they enable complete insulin withdrawal.
The cohort reflected real-world prescribing in the veterans system. Semaglutide accounted for 76.6% of the GLP-1 group, almost all patients in the SGLT2 group received empagliflozin and most DPP-4 users were treated with alogliptin. The researchers also found that younger adults and those taking less than 50 units of insulin a day at baseline were more likely to stop insulin, regardless of which add-on medicine they used. Follow-up analyses, including a less restrictive definition of insulin discontinuation and a per-protocol approach, produced similar results.
The study does suggest that stopping the add-on drug itself is not uncommon. During follow-up, 12.3% of GLP-1 users discontinued therapy, compared with 13.4% of SGLT2 inhibitor users and 26.1% of DPP-4 inhibitor users. Lipska said future work should look at strategies for insulin withdrawal and whether newer incretin-based treatments, including tirzepatide, may change the odds.
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