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Hypoglycemia: a review of definitions used in clinical trials evaluating antihyperglycemic drugs for diabetes

OBJECTIVE: To understand the severity and potential impact of heterogeneity in definitions of hypoglycemia used in diabetes research, we aimed to review the hypoglycemia definitions adopted in randomized controlled trials (RCTs). METHODS: We reviewed 109 RCTs included in the Canadian Agency for Drug...

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Autores principales: Balijepalli, Chakrapani, Druyts, Eric, Siliman, Gaye, Joffres, Michel, Thorlund, Kristian, Mills, Edward J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448700/
https://www.ncbi.nlm.nih.gov/pubmed/28579834
http://dx.doi.org/10.2147/CLEP.S129268
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author Balijepalli, Chakrapani
Druyts, Eric
Siliman, Gaye
Joffres, Michel
Thorlund, Kristian
Mills, Edward J
author_facet Balijepalli, Chakrapani
Druyts, Eric
Siliman, Gaye
Joffres, Michel
Thorlund, Kristian
Mills, Edward J
author_sort Balijepalli, Chakrapani
collection PubMed
description OBJECTIVE: To understand the severity and potential impact of heterogeneity in definitions of hypoglycemia used in diabetes research, we aimed to review the hypoglycemia definitions adopted in randomized controlled trials (RCTs). METHODS: We reviewed 109 RCTs included in the Canadian Agency for Drugs and Technologies in Health reports for the second- and third-line therapy for the patients with type 2 diabetes (T2D). RESULTS: Nearly 60% (n=66) of the studies reviewed presented the definitions for overall hypoglycemia, and another 20% (n=22) of the studies reported the results for hypoglycemia but did not report a definition. Among these 66 studies, only 9 (14%) followed the American Diabetes Association/European Medicines Agency specified guidelines to define hypoglycemia, with an exact threshold of plasma glucose ≤3.9 mmol/L. Fifty-two of the 66 studies (79%) used a threshold considerably lower than the recommended ≤3.9 mmol/L, and 16 studies used a threshold between 3.8 and 4.0 mmol/L. The proportion of the trials that used a cutoff value of <3.1 mmol/L appeared to be slightly similar among the more commonly used non-insulin treatments, GLP-1s (7 of 18 [39%]), thiazolidinediones (TZDs; 6 of 11 [55%]), DPP-4s (12 of 19 [64%]), and sulfonylureas (11 of 20 [55%]). Among trials with intermediate-long-acting insulins (neutral protamine Hagedorn insulin, detemir, glargine), 7 of 26 trials (27%) used a cutoff of <3.1 mmol/L. The definition of severe hypoglycemia was also subject to substantial heterogeneity, in both the utilized threshold and accompanying soft definitions. CONCLUSION: This review demonstrates that substantial heterogeneity exists in the definition of overall, severe/major, and nocturnal hypoglycemia across RCTs investigating T2D interventions.
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spelling pubmed-54487002017-06-02 Hypoglycemia: a review of definitions used in clinical trials evaluating antihyperglycemic drugs for diabetes Balijepalli, Chakrapani Druyts, Eric Siliman, Gaye Joffres, Michel Thorlund, Kristian Mills, Edward J Clin Epidemiol Review OBJECTIVE: To understand the severity and potential impact of heterogeneity in definitions of hypoglycemia used in diabetes research, we aimed to review the hypoglycemia definitions adopted in randomized controlled trials (RCTs). METHODS: We reviewed 109 RCTs included in the Canadian Agency for Drugs and Technologies in Health reports for the second- and third-line therapy for the patients with type 2 diabetes (T2D). RESULTS: Nearly 60% (n=66) of the studies reviewed presented the definitions for overall hypoglycemia, and another 20% (n=22) of the studies reported the results for hypoglycemia but did not report a definition. Among these 66 studies, only 9 (14%) followed the American Diabetes Association/European Medicines Agency specified guidelines to define hypoglycemia, with an exact threshold of plasma glucose ≤3.9 mmol/L. Fifty-two of the 66 studies (79%) used a threshold considerably lower than the recommended ≤3.9 mmol/L, and 16 studies used a threshold between 3.8 and 4.0 mmol/L. The proportion of the trials that used a cutoff value of <3.1 mmol/L appeared to be slightly similar among the more commonly used non-insulin treatments, GLP-1s (7 of 18 [39%]), thiazolidinediones (TZDs; 6 of 11 [55%]), DPP-4s (12 of 19 [64%]), and sulfonylureas (11 of 20 [55%]). Among trials with intermediate-long-acting insulins (neutral protamine Hagedorn insulin, detemir, glargine), 7 of 26 trials (27%) used a cutoff of <3.1 mmol/L. The definition of severe hypoglycemia was also subject to substantial heterogeneity, in both the utilized threshold and accompanying soft definitions. CONCLUSION: This review demonstrates that substantial heterogeneity exists in the definition of overall, severe/major, and nocturnal hypoglycemia across RCTs investigating T2D interventions. Dove Medical Press 2017-05-23 /pmc/articles/PMC5448700/ /pubmed/28579834 http://dx.doi.org/10.2147/CLEP.S129268 Text en © 2017 Balijepalli et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Review
Balijepalli, Chakrapani
Druyts, Eric
Siliman, Gaye
Joffres, Michel
Thorlund, Kristian
Mills, Edward J
Hypoglycemia: a review of definitions used in clinical trials evaluating antihyperglycemic drugs for diabetes
title Hypoglycemia: a review of definitions used in clinical trials evaluating antihyperglycemic drugs for diabetes
title_full Hypoglycemia: a review of definitions used in clinical trials evaluating antihyperglycemic drugs for diabetes
title_fullStr Hypoglycemia: a review of definitions used in clinical trials evaluating antihyperglycemic drugs for diabetes
title_full_unstemmed Hypoglycemia: a review of definitions used in clinical trials evaluating antihyperglycemic drugs for diabetes
title_short Hypoglycemia: a review of definitions used in clinical trials evaluating antihyperglycemic drugs for diabetes
title_sort hypoglycemia: a review of definitions used in clinical trials evaluating antihyperglycemic drugs for diabetes
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448700/
https://www.ncbi.nlm.nih.gov/pubmed/28579834
http://dx.doi.org/10.2147/CLEP.S129268
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