Redefining hypoglycemia in clinical trials: Validation of definitions recently adopted by the American Diabetes Association/European Association for the study of diabetes

Simon R. Heller, John B. Buse, Robert Ratner, Elizabeth Seaquist, Lars Bardtrum, Charlotte Thim Hansen, Deniz Tutkunkardas, Alan C. Moses

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

OBJECTIVE: To determine if the International Hypoglycaemia Study Group (IHSG) level 2 low glucose definition can identify clinically relevant hypoglycemia in clinical trials and offer value as an end point for future trials.

RESEARCH DESIGN AND METHODS: A post hoc analysis was performed of the SWITCH (SWITCH 1: n = 501, type 1 diabetes; SWITCH 2: n = 721, type 2 diabetes) and DEVOTE ( n = 7,637, type 2 diabetes) trials utilizing the IHSG low glucose definitions. Patients in all trials were randomized to either insulin degludec or insulin glargine 100 units/mL. In the main analysis, the following definitions were compared: 1) American Diabetes Association (ADA) 2005 (plasma glucose [PG] confirmed ≤3.9 mmol/L with symptoms); and 2) IHSG level 2 (PG confirmed <3.0 mmol/L, independent of symptoms).

RESULTS: In SWITCH 2, the estimated rate ratios of hypoglycemic events indicated increasing differences between treatments with decreasing PG levels until 3.0 mmol/L, following which no additional treatment differences were observed. Similar results were observed for the SWITCH 1 trial. In SWITCH 2, the IHSG level 2 definition produced a rate ratio that was lower than the ADA 2005 definition.

CONCLUSIONS: The IHSG level 2 definition was validated in a series of clinical trials, demonstrating its ability to discriminate between basal insulins. This definition is therefore recommended to be uniformly adopted by regulatory bodies and used in future clinical trials.

Original languageEnglish (US)
Pages (from-to)398-404
Number of pages7
JournalDiabetes care
Volume43
Issue number2
DOIs
StatePublished - Feb 1 2020

Bibliographical note

Publisher Copyright:
© 2019 by the American Diabetes Association.

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Diabetes Mellitus, Type 1/blood
  • Diabetes Mellitus, Type 2/blood
  • Diagnostic Techniques, Endocrine/standards
  • Europe
  • Female
  • Humans
  • Hypoglycemia/blood
  • Hypoglycemic Agents/therapeutic use
  • Insulin Glargine/therapeutic use
  • Insulin, Long-Acting/therapeutic use
  • Male
  • Middle Aged
  • Practice Guidelines as Topic/standards
  • Randomized Controlled Trials as Topic/methods
  • Reference Standards
  • Reference Values
  • Societies, Medical/organization & administration
  • Terminology as Topic
  • United States
  • Young Adult

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Validation Study

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