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

Julie Z. Zhao; Eric D. Weinhandl; Angeline M. Carlson; Wendy L. St. Peter

doi:10.1016/j.xkme.2022.100510

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

Julie Z. Zhao, Eric D. Weinhandl, Angeline M. Carlson, Wendy L. St. Peter

Pharmaceutical Care and Health Systems

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

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.

Original language	English (US)
Article number	100510
Journal	Kidney Medicine
Volume	4
Issue number	8
DOIs	https://doi.org/10.1016/j.xkme.2022.100510
State	Published - Aug 2022

Bibliographical note

Funding Information:
Julie Z. Zhao, MPH, PhD, Eric D. Weinhandl, PhD, MS, Angeline M. Carlson, PhD, and Wendy L. St. Peter, PharmD, Research idea and study design: JZZ, AMC, WLSP; data acquisition: JZZ, EDW, WLSP; data analysis/interpretation: JZZ, EDW, WLSP; statistical analysis: JZZ, EDW, WLSP; supervision or mentorship: WLSP. Each author contributed important intellectual content during manuscript drafting or revision, accepts personal accountability for the author's own contributions, and agrees to ensure that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. None. The authors declare that they have no relevant financial interests. We would like to acknowledge the support that Jon Schommer, PhD and Weihua Guan, PhD, University of Minnesota, provided as advisors on JZZ's PhD dissertation committee. The data reported here have been supplied by the Centers for Medicare & Medicaid Services. The authors received no specific funding for this work. The data reported here have been supplied by the Centers for Medicare & Medicaid Services (CMS). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the U.S. Government. Received January 17, 2022. Evaluated by 2 external peer reviewers, with direct editorial input by a Statistical Editor and the Editor-in-Chief. Accepted in revised form May 11, 2022.

Publisher Copyright:
© 2022 The Authors

Keywords

Chronic kidney disease (CKD)
Medicare claims data
glucose-lowering medications
hypoglycemia
type 2 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.xkme.2022.100510

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@article{f2d025be9aaa4d85a1e022ae418cae53,

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

abstract = "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.",

keywords = "Chronic kidney disease (CKD), Medicare claims data, glucose-lowering medications, hypoglycemia, type 2 diabetes",

author = "Zhao, {Julie Z.} and Weinhandl, {Eric D.} and Carlson, {Angeline M.} and {St. Peter}, {Wendy L.}",

note = "Funding Information: Julie Z. Zhao, MPH, PhD, Eric D. Weinhandl, PhD, MS, Angeline M. Carlson, PhD, and Wendy L. St. Peter, PharmD, Research idea and study design: JZZ, AMC, WLSP; data acquisition: JZZ, EDW, WLSP; data analysis/interpretation: JZZ, EDW, WLSP; statistical analysis: JZZ, EDW, WLSP; supervision or mentorship: WLSP. Each author contributed important intellectual content during manuscript drafting or revision, accepts personal accountability for the author's own contributions, and agrees to ensure that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. None. The authors declare that they have no relevant financial interests. We would like to acknowledge the support that Jon Schommer, PhD and Weihua Guan, PhD, University of Minnesota, provided as advisors on JZZ's PhD dissertation committee. The data reported here have been supplied by the Centers for Medicare & Medicaid Services. The authors received no specific funding for this work. The data reported here have been supplied by the Centers for Medicare & Medicaid Services (CMS). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the U.S. Government. Received January 17, 2022. Evaluated by 2 external peer reviewers, with direct editorial input by a Statistical Editor and the Editor-in-Chief. Accepted in revised form May 11, 2022. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = aug,

doi = "10.1016/j.xkme.2022.100510",

language = "English (US)",

volume = "4",

journal = "Kidney Medicine",

issn = "2590-0595",

publisher = "Elsevier Inc.",

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TY - JOUR

T1 - Hypoglycemia Risk With SGLT2 Inhibitors or Glucagon-Like Peptide 1 Receptor Agonists Versus Sulfonylureas Among Medicare Insured Adults With CKD in the United States

AU - Zhao, Julie Z.

AU - Weinhandl, Eric D.

AU - Carlson, Angeline M.

AU - St. Peter, Wendy L.

N1 - Funding Information: Julie Z. Zhao, MPH, PhD, Eric D. Weinhandl, PhD, MS, Angeline M. Carlson, PhD, and Wendy L. St. Peter, PharmD, Research idea and study design: JZZ, AMC, WLSP; data acquisition: JZZ, EDW, WLSP; data analysis/interpretation: JZZ, EDW, WLSP; statistical analysis: JZZ, EDW, WLSP; supervision or mentorship: WLSP. Each author contributed important intellectual content during manuscript drafting or revision, accepts personal accountability for the author's own contributions, and agrees to ensure that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. None. The authors declare that they have no relevant financial interests. We would like to acknowledge the support that Jon Schommer, PhD and Weihua Guan, PhD, University of Minnesota, provided as advisors on JZZ's PhD dissertation committee. The data reported here have been supplied by the Centers for Medicare & Medicaid Services. The authors received no specific funding for this work. The data reported here have been supplied by the Centers for Medicare & Medicaid Services (CMS). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the U.S. Government. Received January 17, 2022. Evaluated by 2 external peer reviewers, with direct editorial input by a Statistical Editor and the Editor-in-Chief. Accepted in revised form May 11, 2022. Publisher Copyright: © 2022 The Authors

PY - 2022/8

Y1 - 2022/8

N2 - 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.

AB - 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.

KW - Chronic kidney disease (CKD)

KW - Medicare claims data

KW - glucose-lowering medications

KW - hypoglycemia

KW - type 2 diabetes

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

Abstract

Bibliographical note

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UN SDGs

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