Comparative effectiveness of insulin glargine, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors in veterans with type 2 diabetes.

Aims: To compare the risk of all-cause death and cardiovascular events in new users of insulin glargine, glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), particularly in subgroups defined by baseline haemoglobin A1C (HbA1C), body mass index (BMI) and estimated glomerular filtration rate (eGFR).

Materials And Methods: We conducted an active comparator, new user design study in a national cohort of 161 405 veterans with type 2 diabetes (T2D) on metformin and initiated insulin glargine (n = 54 375), GLP-1RA (n = 22 145) or SGLT2i (n = 84 885) between 1 January 2018 and 31 December 2021. Patients were followed until 31 March 2023. Inverse probability weighted Cox regression models were used for treatment comparisons on all-cause deaths and cardiovascular events in the entire cohort and above subgroups.

Results: There were 20 788 cardiovascular events/414 414 person-years and 15 268 all-cause deaths/446 458 person-years. Insulin glargine had a higher hazard of all-cause death compared to GLP-1RA (hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.48-1.67) or SGLT2i (HR 1.55, 95% CI 1.48-1.61) in the entire cohort and across subgroups, especially in those with HbA1C levels <9.0%. Results were similar for secondary outcomes. Compared to GLP-1RA, SGLT2i had similar risk of all-cause death (HR 1.03, 95% CI 0.97-1.10) but higher hazard of cardiovascular events (HR 1.13, 95% CI 1.08-1.19). Across subgroups, GLP-1RA and SGLT2i had generally similar effects, with SGLT2i showing a slightly higher risk in some cases.

Conclusions: Insulin glargine might be deleterious particularly in those with HbA1C <9.0%. There was no clear evidence for prioritization of SGLT2i versus GLP-1RA across subgroups.