Hypoglycemia Risk With SGLT2 Inhibitors or Glucagon-Like Peptide 1 Receptor Agonists Versus Sulfonylureas Among Medicare Insured Adults With CKD in the United States.

Rationale & Objective: Information on safety issues of newer glucose-lowering medications from a large population perspective in chronic kidney disease (CKD) patients with type 2 diabetes is limited. Our study aimed to examine hypoglycemia risk associated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) versus second-generation sulfonylureas in a general population of older patients with CKD and type 2 diabetes, across race, age, sex, and socioeconomic subgroups.

Study Design: Retrospective cohort.

Setting & Participants: The 20% random sample of Medicare fee-for-service claims, 2012-2018.

Exposures: Use of SGLT2is, GLP-1RAs, or sulfonylureas.

Outcomes: Hypoglycemic events resulting in health care utilization.

Analytical Approach: Cox proportional hazard model evaluated the 90-day risk of hypoglycemia associated with SGLT2is or GLP-1RAs versus sulfonylureas.

Results: A total of 18,567 adults (mean age: 73 years) with CKD and type 2 diabetes was included; 14.0% ( n = 2,528) had a prescription for a SGLT2i or GLP-1RA, and 86.0% ( n = 16,039) with a sulfonylurea. Compared with sulfonylureas, use of SGLT2is or GLP-1RAs was associated with a significantly lower risk of hypoglycemia (adjusted HR, 0.30; 95% CI, 0.14-0.65). Black individuals had higher risk of developing hypoglycemia than White individuals (adjusted HR, 1.55; 95% CI, 1.07-2.26). Low-income subsidy compared to no low-income subsidy status was associated with higher risk of hypoglycemic events. The risk of hypoglycemia also increased with higher comorbid condition score.

Limitations: CKD and type 2 diabetes diagnosis, CKD stage, and patient clinical status were identified with diagnosis or procedure codes. There is potential for residual confounding with use of retrospective data.

Conclusions: Use of SGLT2is or GLP-1RAs compared with sulfonylureas was associated with a lower risk of hypoglycemia among patients with CKD and type 2 diabetes. Black race was not only associated with lower use of newer agents with demonstrated cardiovascular and kidney benefits and lower hypoglycemia risk, but also with a higher rate of hypoglycemic events as compared with White individuals.