Glycemia Reduction in Type 2 Diabetes - Glycemic Outcomes

Authors

David M Nathan
John M Lachin
Ashok Balasubramanyam
Henry B Burch
John B Buse
Nicole M Butera
Robert M Cohen
Jill P Crandall
Steven E Kahn
Heidi Krause-Steinrauf
Mary E Larkin
Neda Rasouli
Margaret Tiktin
Deborah J Wexler
Naji Younes

Publication Date

9-22-2022

Journal

The New England Journal of Medicine

DOI

10.1056/NEJMoa2200433

PMID

36129996

PMCID

PMC9829320

PubMedCentral® Posted Date

3-22-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Blood Glucose, Comparative Effectiveness Research, Diabetes Mellitus, Type 2, Dipeptidyl-Peptidase IV Inhibitors, Drug Therapy, Combination, Glucagon-Like Peptide-1 Receptor, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin Glargine, Liraglutide, Metformin, Sitagliptin Phosphate, Sulfonylurea Compounds, Treatment Outcome

Abstract

BACKGROUND: The comparative effectiveness of glucose-lowering medications for use with metformin to maintain target glycated hemoglobin levels in persons with type 2 diabetes is uncertain.

METHODS: In this trial involving participants with type 2 diabetes of less than 10 years' duration who were receiving metformin and had glycated hemoglobin levels of 6.8 to 8.5%, we compared the effectiveness of four commonly used glucose-lowering medications. We randomly assigned participants to receive insulin glargine U-100 (hereafter, glargine), the sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or sitagliptin, a dipeptidyl peptidase 4 inhibitor. The primary metabolic outcome was a glycated hemoglobin level, measured quarterly, of 7.0% or higher that was subsequently confirmed, and the secondary metabolic outcome was a confirmed glycated hemoglobin level greater than 7.5%.

RESULTS: A total of 5047 participants (19.8% Black and 18.6% Hispanic or Latinx) who had received metformin for type 2 diabetes were followed for a mean of 5.0 years. The cumulative incidence of a glycated hemoglobin level of 7.0% or higher (the primary metabolic outcome) differed significantly among the four groups (P

CONCLUSIONS: All four medications, when added to metformin, decreased glycated hemoglobin levels. However, glargine and liraglutide were significantly, albeit modestly, more effective in achieving and maintaining target glycated hemoglobin levels. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; GRADE ClinicalTrials.gov number, NCT01794143.).

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