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Abstract: SA-PO483

Increased Risk of Serious Hypoglycemia 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, University of Utah Health, 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
  • Mohammed, Azeem Mohiuddin, University of Utah Health, Salt Lake City, Utah, United States
  • Kim, David, University of Utah Health, Salt Lake City, Utah, United States
  • Bissada, George, University of Utah Health, Salt Lake City, Utah, United States
  • Akrami, Farahnaz, University of Utah Health, 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

Serious hypoglycemic events needing medical attention are significant complications of anti-glycemic therapy in type 2 diabetes (T2D), particularly in those with CKD. Therefore we examined the risk of serious hypoglycemic events with insulin glargine (IG) use compared to glucagon-like peptide-1 receptor agonists) GLP1-RA and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in a national cohort of veterans.

Methods

We conducted an active comparator, new user design study of veterans (N = 30165 ) with T2D with CKD (eGFR < 60) on metformin who then initiated on IG or SGLT2i or GLP1-RA for the first time between 01/01/2018 to 12/31/2021. Those with any previous use of these agents were excluded. Administrative censor date was 03/31/2023. Serious hypoglycemic events needing medical attention were identified from ER/ urgent care visits or hospital discharge diagnosis with ICD10 codes using a validated algorithm . Inverse probability weights (IPW) were developed using propensity scores for the three drug classes. In IPW Cox models, the study drug classes were related to the risk of serious hypoglycemic events.

Results

38.2% were initiated on IG, 12.7% on GLP1-RA and 49.1% on SGLT2i. Mean eGFR was 79.5± 20.1 ml/min/1.73m2. There were 972 events over 78594 years follow-up. In IPW Cox regression, compared to GLP1-RA, the IG group had higher risk whereas the SGLT2i group had lower risk (Table 1).

Conclusion

IG is associated with higher serious hypoglycemia risk in CKD . The safety of IG in CKD needs to be reevaluated.

Table 1. Risk of hypoglycemia by drug class and CKD
 Event RateHR (95% CI)
Non-CKD (N= 128774)0.71 
GLP1-RA (N = 16355)0.521.00
Insulin Glargine (N = 49821)1.091.59 (1.39, 1.82)
SGLT2i (N = 62598)0.420.70 (0.60, 0.81)
CKD (N = 30165)1.24 
GLP1-RA (N = 3787)1.061.00
Insulin Glargine (N = 10901)1.881.49 (1.21, 1.83)
SGLT2i (N = 15477)0.740.67 (0.54, 0.83)