Hypoglycemia Risk With SGLT2 Inhibitors or Glucagon-Like Peptide 1 Receptor Agonists Versus Sulfonylureas Among Medicare Insured Adults With CKD in the United States
Open accessAbstract
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: = 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.
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Studies have shown that racial disparity persists at all levels of social economic status.
“Similar to our finding, studies have shown that racial disparity persists at all levels of social economic status.26,27”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [27]
The Results (Table 4; page unavailable) report higher hypoglycemia risk for Black than White patients and include low-income subsidy status as a socioeconomic measure. That adjusted finding supports a racial disparity, but the paper does not show that it persists at all socioeconomic levels. (LLM, conf=0.86)
Experimental — accuracy not yet measuredOur research team showed that Medicare-enrolled Black patients with CKD had a higher risk of developing hypoglycemia than White patients.
“Our research team showed that Medicare-enrolled Black patients with CKD had a higher risk of developing hypoglycemia than White patients.30”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [30]
Health disparities in Black patients with diabetes and CKD have been well documented.
“Health disparities in Black patients with diabetes and CKD have been well documented.”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [30]
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- Authors
- Zhao, J. Z., Weinhandl, E. D., Carlson, A. M., & St. Peter, W. L.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Zhao, Julie Z.
- ORCID
- Weinhandl, Eric D.
- Venue
- Kidney Medicine
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 4
- Issue
- 8
- Pages
- 100510
- ISSN
- 2590-0595 (ISSN-L)
- PMC
- PMC9310119
- OpenAlex
- W4283574208
- Cited by
- 26
- References
- 25
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 6 · 2023: 6 · 2022: 1
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Kidney Medicine (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Centers for Medicare and Medicaid Services
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- hypoglycemia, SGLT2 inhibitors, GLP-1 receptor agonists, sulfonylureas, chronic kidney disease, type 2 diabetes, racial disparities, Black patients, low-income subsidy, comorbidities, fee-for-service Medicare, glucose-lowering medications, health care utilization, older adults, socioeconomic status, drug safety
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