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HbA(1c) Change and Diabetic Retinopathy During GLP-1 Receptor Agonist Cardiovascular Outcome Trials: A Meta-analysis and Meta-regression

BACKGROUND: Long-term glycemic control reduces retinopathy risk, but transient worsening can occur with glucose control intensification. Glucagon-like peptide 1 receptor agonists (GLP-1RA) lower glucose, but the long-term impact on retinopathy is unknown. GLP-1RA cardiovascular outcome trials (CVOTs...

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Autores principales: Bethel, M. Angelyn, Diaz, Rafael, Castellana, Noelia, Bhattacharya, Indranil, Gerstein, Hertzel C., Lakshmanan, Mark C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783944/
https://www.ncbi.nlm.nih.gov/pubmed/33444163
http://dx.doi.org/10.2337/dc20-1815
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author Bethel, M. Angelyn
Diaz, Rafael
Castellana, Noelia
Bhattacharya, Indranil
Gerstein, Hertzel C.
Lakshmanan, Mark C.
author_facet Bethel, M. Angelyn
Diaz, Rafael
Castellana, Noelia
Bhattacharya, Indranil
Gerstein, Hertzel C.
Lakshmanan, Mark C.
author_sort Bethel, M. Angelyn
collection PubMed
description BACKGROUND: Long-term glycemic control reduces retinopathy risk, but transient worsening can occur with glucose control intensification. Glucagon-like peptide 1 receptor agonists (GLP-1RA) lower glucose, but the long-term impact on retinopathy is unknown. GLP-1RA cardiovascular outcome trials (CVOTs) provide long-term follow-up, allowing examination of retinopathy outcomes. PURPOSE: To examine the associations between retinopathy, HbA(1c), systolic blood pressure (SBP), and weight in GLP-1RA CVOTs. DATA SOURCES: Systematic review identified six placebo-controlled GLP-1RA CVOTs reporting prespecified retinopathy outcomes. STUDY SELECTION: Published trial reports were used as the primary data sources. DATA EXTRACTION: HbA(1c), SBP, and weight data throughout follow-up by treatment group were extracted. DATA SYNTHESIS: Random-effects model meta-analysis showed no association between GLP-1RA treatment and retinopathy (odds ratio [OR] 1.10; 95% CI 0.93, 1.30), with high heterogeneity between studies (I(2) = 52.2%; Q statistic P = 0.063). Univariate meta-regression showed an association between retinopathy and average HbA(1c) reduction during the overall follow-up (slope = 0.77, P = 0.007), but no relationship for SBP or weight. Sensitivity analyses for HbA(1c) showed a relationship at 3 months (P = 0.006) and 1 year (P = 0.002). A 0.1% (1.09 mmol/mol) increase in HbA(1c) reduction was associated with 6%, 14%, or 8% increased Ln(OR) for retinopathy at the 3-month, 1-year, and overall follow-up, respectively. LIMITATIONS: CVOTs were not powered to assess retinopathy outcomes and differed in retinopathy-related criteria and methodology. The median follow-up of 3.4 years is short compared with the onset of retinopathy. CONCLUSIONS: HbA(1c) reduction was significantly associated with increased retinopathy risk in meta-regression for GLP-1RA CVOTs. The magnitude of HbA(1c) reduction was correlated with retinopathy risk in people with diabetes and additional cardiovascular risk factors, but the long-term impact of improved glycemic control on retinopathy was unmeasured in these studies. Retinopathy status should be assessed when intensifying glucose-lowering therapy.
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spelling pubmed-77839442021-01-12 HbA(1c) Change and Diabetic Retinopathy During GLP-1 Receptor Agonist Cardiovascular Outcome Trials: A Meta-analysis and Meta-regression Bethel, M. Angelyn Diaz, Rafael Castellana, Noelia Bhattacharya, Indranil Gerstein, Hertzel C. Lakshmanan, Mark C. Diabetes Care Meta-Analysis BACKGROUND: Long-term glycemic control reduces retinopathy risk, but transient worsening can occur with glucose control intensification. Glucagon-like peptide 1 receptor agonists (GLP-1RA) lower glucose, but the long-term impact on retinopathy is unknown. GLP-1RA cardiovascular outcome trials (CVOTs) provide long-term follow-up, allowing examination of retinopathy outcomes. PURPOSE: To examine the associations between retinopathy, HbA(1c), systolic blood pressure (SBP), and weight in GLP-1RA CVOTs. DATA SOURCES: Systematic review identified six placebo-controlled GLP-1RA CVOTs reporting prespecified retinopathy outcomes. STUDY SELECTION: Published trial reports were used as the primary data sources. DATA EXTRACTION: HbA(1c), SBP, and weight data throughout follow-up by treatment group were extracted. DATA SYNTHESIS: Random-effects model meta-analysis showed no association between GLP-1RA treatment and retinopathy (odds ratio [OR] 1.10; 95% CI 0.93, 1.30), with high heterogeneity between studies (I(2) = 52.2%; Q statistic P = 0.063). Univariate meta-regression showed an association between retinopathy and average HbA(1c) reduction during the overall follow-up (slope = 0.77, P = 0.007), but no relationship for SBP or weight. Sensitivity analyses for HbA(1c) showed a relationship at 3 months (P = 0.006) and 1 year (P = 0.002). A 0.1% (1.09 mmol/mol) increase in HbA(1c) reduction was associated with 6%, 14%, or 8% increased Ln(OR) for retinopathy at the 3-month, 1-year, and overall follow-up, respectively. LIMITATIONS: CVOTs were not powered to assess retinopathy outcomes and differed in retinopathy-related criteria and methodology. The median follow-up of 3.4 years is short compared with the onset of retinopathy. CONCLUSIONS: HbA(1c) reduction was significantly associated with increased retinopathy risk in meta-regression for GLP-1RA CVOTs. The magnitude of HbA(1c) reduction was correlated with retinopathy risk in people with diabetes and additional cardiovascular risk factors, but the long-term impact of improved glycemic control on retinopathy was unmeasured in these studies. Retinopathy status should be assessed when intensifying glucose-lowering therapy. American Diabetes Association 2021-01 2020-12-14 /pmc/articles/PMC7783944/ /pubmed/33444163 http://dx.doi.org/10.2337/dc20-1815 Text en © 2020 by the American Diabetes Association https://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.
spellingShingle Meta-Analysis
Bethel, M. Angelyn
Diaz, Rafael
Castellana, Noelia
Bhattacharya, Indranil
Gerstein, Hertzel C.
Lakshmanan, Mark C.
HbA(1c) Change and Diabetic Retinopathy During GLP-1 Receptor Agonist Cardiovascular Outcome Trials: A Meta-analysis and Meta-regression
title HbA(1c) Change and Diabetic Retinopathy During GLP-1 Receptor Agonist Cardiovascular Outcome Trials: A Meta-analysis and Meta-regression
title_full HbA(1c) Change and Diabetic Retinopathy During GLP-1 Receptor Agonist Cardiovascular Outcome Trials: A Meta-analysis and Meta-regression
title_fullStr HbA(1c) Change and Diabetic Retinopathy During GLP-1 Receptor Agonist Cardiovascular Outcome Trials: A Meta-analysis and Meta-regression
title_full_unstemmed HbA(1c) Change and Diabetic Retinopathy During GLP-1 Receptor Agonist Cardiovascular Outcome Trials: A Meta-analysis and Meta-regression
title_short HbA(1c) Change and Diabetic Retinopathy During GLP-1 Receptor Agonist Cardiovascular Outcome Trials: A Meta-analysis and Meta-regression
title_sort hba(1c) change and diabetic retinopathy during glp-1 receptor agonist cardiovascular outcome trials: a meta-analysis and meta-regression
topic Meta-Analysis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783944/
https://www.ncbi.nlm.nih.gov/pubmed/33444163
http://dx.doi.org/10.2337/dc20-1815
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