Glycemia reduction in type 2 diabetes-Hypoglycemia outcomes: A randomized clinical trial

Authors

Elizabeth R. Seaquist, Department of Medicine, Division of Diabetes and Endocrinology, University of Minnesota Medical School, Minneapolis, MN, United States of America.
Lawrence S. Phillips, Department of Medicine, Atlanta VA Medical Center, Decatur, GA and Division of Endocrinology and Metabolism, Emory University School of Medicine, Atlanta, GA, United States of America.
Alokananda Ghosh, Department of Biostatistics and Bioinformatics, Milken Institute of Public Health, The Biostatistics Center, The George Washington University, Rockville, MD, United States of America.
Chelsea Baker, Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Colorado School of Medicine, Aurora, CO, United States of America.
Richard M. Bergenstal, Health Partners Institute, International Diabetes Center, Minneapolis, MN, United States of America.
Jill P. Crandall, Division of Endocrinology and Fleischer Institute for Diabetes & Metabolism, Albert Einstein College of Medicine, Bronx, NY, United States of America.
Robin S. Goland, Departments of Medicine and Pediatrics, Naomi Berrie Diabetes Center, Columbia University, New York, NY, United States of America.
Michaela R. Gramzinski, Department of Biostatistics and Bioinformatics, Milken Institute of Public Health, The Biostatistics Center, The George Washington University, Rockville, MD, United States of America.
Sophia H. Hox, Department of Veterans Affairs Pacific Islands Health Care System, Honolulu, HI, United States of America.
Daniel S. Hsia, Clinical Trials Unit, Pennington Biomedical Research Center, Baton Rouge, LA, United States of America.
Mary L. Johnson, Health Partners Institute, International Diabetes Center, Minneapolis, MN, United States of America.
John M. Lachin, Department of Biostatistics and Bioinformatics, Milken Institute of Public Health, The Biostatistics Center, The George Washington University, Rockville, MD, United States of America.
Philip Raskin, University of Texas-Southwestern Medical Center, Dallas, TX, United States of America.
Willy M. Valencia, Geriatric Research Education and Clinical Center, Bruce W. Carter Veterans Affairs Center, Miami, FL, United States of America.
Andrea H. Waltje, University of Michigan, Ann Arbor, MI, United States of America.
Naji Younes, Department of Biostatistics and Bioinformatics, Milken Institute of Public Health, The Biostatistics Center, The George Washington University, Rockville, MD, United States of America.

Document Type

Journal Article

Publication Date

1-1-2024

Journal

PloS one

Volume

19

Issue

11

DOI

10.1371/journal.pone.0309907

Abstract

OBJECTIVE: Hypoglycemia is a major concern in type 2 diabetes (T2DM), but little is known about its likelihood compared across common therapies. We compared the likelihood of hypoglycemia among metformin-treated patients with T2DM randomized to the addition of one of 4 common therapies. RESEARCH DESIGN & METHODS: Randomized, controlled trial of 5,047 participants with T2DM of <10 years' duration, hemoglobin A1c (HbA1c) 6.8-8.5% (50.8-69.4 mmol/mol). Randomization to addition of glargine U100, glimepiride, liraglutide, or sitagliptin over 5.0 ± 1.3 (mean ± SD) years. HbA1c was measured quarterly; if a level >7.5% (>58.5 mmol/mol) was confirmed, rescue glargine and/or aspart insulin was added. We conducted a per-protocol analysis of 4,830, who attended at least one post-baseline visit and took at least one dose of assigned study medication. We assessed severe hypoglycemia events reported throughout the entire study. At quarterly visits, all participants were asked about hypoglycemic symptoms within the last 30 days, and those in the glargine and glimepiride groups were asked for any measured glucose <70 mg/dL (3.9 mmol/L) within this time period. RESULTS: While participants were taking their assigned medications, severe hypoglycemia occurred in 10 (0.8%), 16 (1.3%), 6 (0.5%), and 4 (0.3%), (p<0.05) and hypoglycemic symptoms in 659 (54.2%), 833 (68.3%), 375 (32.4%), and 361 (29.1%) of participants following randomization to glargine, glimepiride, liraglutide, and sitagliptin, respectively (p<0.001). CONCLUSIONS: In metformin-treated patients with T2DM who add a second medication, hypoglycemia is most likely with addition of glimepiride, less with glargine, and least likely with liraglutide and sitagliptin. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01794143.

APA Citation

Seaquist, Elizabeth R.; Phillips, Lawrence S.; Ghosh, Alokananda; Baker, Chelsea; Bergenstal, Richard M.; Crandall, Jill P.; Goland, Robin S.; Gramzinski, Michaela R.; Hox, Sophia H.; Hsia, Daniel S.; Johnson, Mary L.; Lachin, John M.; Raskin, Philip; Valencia, Willy M.; Waltje, Andrea H.; and Younes, Naji, "Glycemia reduction in type 2 diabetes-Hypoglycemia outcomes: A randomized clinical trial" (2024). GW Authored Works. Paper 6001.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/6001

Department

Biostatistics and Bioinformatics