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Kidney Week

Abstract: SA-PO484

Increased Mortality Risk with Insulin Glargine in Veterans with Type 2 Diabetes: An Emulated Clinical Trial Observational Study

Session Information

Category: Diabetic Kidney Disease

  • 702 Diabetic Kidney Disease: Clinical

Authors

  • Sarwal, Amara, VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
  • Shen, Jincheng, VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
  • Singh, Ravinder, VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
  • Nevers, Mckenna R., VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
  • Hartsell, Sydney Elizabeth, VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
  • Wei, Guo, VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
  • Boucher, Robert E., VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
  • Adams, Brad, VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
  • Christensen, Jesse, VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
  • Greene, Tom, VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
  • Beddhu, Srinivasan, VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
Background

Insulin glargine (IG) is one of the most commonly used anti-glycemic agents in advanced CKD. However, there is a paucity of data in head to head comparisons of IG with newer agents like glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Therefore we examined the risk of mortality with insulin glargine use compared to GLP1-RA and SGLT2i use in a national cohort of veterans.

Methods

We followed the active comparator, new user design to emulate a trial to compare the effect of initiating on IG or SGLT2i or GLP1-RA among veterans with T2D on metformin who initiated any one of these three between 01/01/2018 to 12/31/2021 (N = 158,939). Those with previous use of these agents were excluded. Administrative censor date was 03/31/2023. Generalized propensity score based inverse probability weighting (IPW) was employed to control confounding in the observational data and facilitate comparisons among the three drug classes. In IPW Cox models, the study drug classes were related to the risk of mortality in those without and with CKD (eGFR < 60).

Results

38.2% were initiated on IG, 12.7% on GLP1-RA and 49.1% on SGLT2i. 19% had CKD. There were 11,109 deaths over 368,347 patient-years of follow-up in non-CKD and 4,660 deaths over 80,043 patient-years in CKD patients. In IPW Cox regression, compared to GLP1-RA, the IG group had higher mortality risk in both the non-CKD and CKD subgroups whereas the SGLT2i group had lower mortality in the CKD subgroup (Table).

Conclusion

IG is associated with higher mortality risk in both non-CKD and CKD subgroups. These results suggest that the routine clinical use of IG needs to be reconsidered.

Table 1. Mortality events
 Event RateHR (95% CI)
Non-CKD (N= 128774)  
GLP1-RA (N = 16355)1.961.00
Insulin Glargine (N = 49821)4.141.70 (1.59, 1.83)
SGLT2i (N = 62598)2.260.95 (0.88, 1.02)
CKD (N = 30165)  
GLP1-RA (N = 3787)4.801.00
Insulin Glargine (N = 10901)7.911.39 (1.26, 1.53)
SGLT2i (N = 15477)4.310.82 (0.74, 0.90)