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Glycated hemoglobin as a surrogate for evaluating the effectiveness of drugs in diabetes mellitus trials: a systematic review and trial-level meta-analysis

Published online by Cambridge University Press:  22 December 2021

Paola Andrea Rivera Open the ORCID record for Paola Andrea Rivera [Opens in a new window] ,
Milton J. M. Rodríguez-Zúñiga ,
José Caballero-Alvarado  and
Fabián Fiestas
Paola Andrea Rivera*
Affiliation:
Escuela de Posgrado, Universidad Privada Antenor Orrego, Trujillo, Peru
Milton J. M. Rodríguez-Zúñiga
Affiliation:
Escuela de Posgrado, Universidad Nacional Mayor de San Marcos, Lima, Peru
José Caballero-Alvarado
Affiliation:
Escuela de Posgrado, Universidad Privada Antenor Orrego, Trujillo, Peru
Fabián Fiestas
Affiliation:
Instituto de Gestión y Evaluación de Tecnologías Sanitarias, Lima, Peru
*
Author for correspondence: Paola Andrea Rivera, E-mail: priverar2@upao.edu.pe
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Abstract

Objective

The objective of this study was to investigate whether glycated hemoglobin (HbA1c) is a valid surrogate for evaluating the effectiveness of antihyperglycemic drugs in diabetes mellitus (DM) trials.

Methods

We conducted a systematic review of placebo-controlled randomized clinical trials (RCTs) evaluating the effect of a treatment on HbA1c (mean difference between groups) and clinical outcomes (relative risk of mortality, myocardial infarction, stroke, heart failure, and/or kidney injury) in patients with DM. Then, we investigated the association between treatment effects on HbA1c and clinical outcomes using regression analysis at the trial level. Lastly, we interpreted the correlation coefficients (R) using the cut-off points suggested by the Institute for Quality and Efficiency in Healthcare (IQWiG). HbA1c was considered a valid surrogate if it demonstrated a strong association: lower limit of the 95 percent confidence interval (95 percent CI) of R greater than or equal to .85.

Results

Nineteen RCTs were identified. All studies included adults with type 2 DM. None of the associations evaluated was strong enough to validate HbA1c as a surrogate for any clinical outcome: mortality (R = .34; 95 percent CI −.14 to .69), myocardial infarction (R = .20; −.30 to .61), heart failure (R = .08; −.40 to .53), kidney injury (R = −.04; −.52 to .47), and stroke (R = .81; .54 to .93).

Conclusions

The evidence from multiple placebo-controlled RCTs does not support the use of HbA1c as a surrogate to measure the effectiveness of antihyperglycemic drugs in DM studies.

Keywords

Diabetes mellitusGlycated hemoglobin aCardiovascular diseasesHypoglycemic agentsSurrogate end points
Type
Assessment
Information
International Journal of Technology Assessment in Health Care , Volume 38 , Issue 1 , 2022 , e12
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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