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

🥉 Top 5% JournalJan 31, 2025Diabetes, obesity & metabolism

Comparing insulin glargine, GLP-1 receptor drugs, and SGLT-2 inhibitors in veterans with type 2 diabetes

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Abstract

In a cohort of 161,405 veterans with type 2 diabetes, insulin glargine was associated with a 57% higher risk of all-cause death compared to glucagon-like peptide-1 receptor agonists (GLP-1RA).

Insulin glargine showed a higher hazard of all-cause death compared to both GLP-1RA and sodium-glucose cotransporter-2 inhibitors (SGLT2i).
The hazard ratio for all-cause death was 1.57 for insulin glargine versus GLP-1RA and 1.55 versus SGLT2i in the entire cohort.
The increased risk of death was particularly pronounced in patients with hemoglobin A1C levels below 9.0%.
SGLT2i had a similar risk of all-cause death compared to GLP-1RA but a higher hazard for cardiovascular events.
The findings suggest that effects of GLP-1RA and SGLT2i were generally similar across subgroups, with some instances of increased risk for SGLT2i.

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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.

Key numbers

1.57

Higher Hazard of All-Cause Death

for all-cause death with insulin glargine vs.

1.13

Higher Hazard of Cardiovascular Events

for cardiovascular events with vs.

15 268

All-Cause Deaths in Follow-Up

Number of all-cause deaths over 446 458 person-years of follow-up

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Abstract

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