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% ( = 2,528) had a prescription for a SGLT2i or GLP-1RA, and 86.0% ( = 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.