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Glucagon-like peptide-1 receptor agonists and diabetic retinopathy : nationwide cohort and Mendelian randomization studies

Zheng, Deqiang LU ; Li, Ning ; Hou, Rui ; Zhang, Xiaoyu ; Wu, Lijuan ; Sundquist, Jan LU ; Sundquist, Kristina LU and Ji, Jianguang LU orcid (2023) In BMC Medicine 21. p.1-10
Abstract

BACKGROUND: The ability of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to decrease certain microvascular events has called for the investigation of GLP-1 RAs against diabetic retinopathy (DR), but the evidence is limited. By combining data from observational and Mendelian randomization (MR) studies, we aimed to investigate whether GLP-1 RAs decrease the risk of DR.

METHODS: We combined data from several Swedish Registers and identified patients with incident type 2 diabetes being treated with GLP-1 RAs between 2006 and 2015, and matched them to diabetic patients who did not use GLP-1 RAs as the comparisons. The Cox proportional hazards models were applied to assess the risk of DR. We further performed the... (More)

BACKGROUND: The ability of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to decrease certain microvascular events has called for the investigation of GLP-1 RAs against diabetic retinopathy (DR), but the evidence is limited. By combining data from observational and Mendelian randomization (MR) studies, we aimed to investigate whether GLP-1 RAs decrease the risk of DR.

METHODS: We combined data from several Swedish Registers and identified patients with incident type 2 diabetes being treated with GLP-1 RAs between 2006 and 2015, and matched them to diabetic patients who did not use GLP-1 RAs as the comparisons. The Cox proportional hazards models were applied to assess the risk of DR. We further performed the summary-data-based MR (SMR) analyses based on the Genotype-Tissue Expression databases and the Genome-Wide Association Study of DR from the FinnGen consortium.

RESULTS: A total of 2390 diabetic patients were treated with GLP-1 RAs and the incidence of DR was 5.97 per 1000 person-years. Compared with diabetic patients who did not use GLP-1 RAs having an incidence of 12.85 per 1000 person-years, the adjusted hazard ratio (HR) of DR was 0.42 [95% confidence interval (CI), 0.29-0.61]. Genetically-predicted GLP1R expression (the target of GLP-1 RAs) showed an inverse association with background [odds ratio (OR)=0.83, 95% CI, 0.71-0.97] and severe nonproliferative DR (OR=0.72, 95% CI, 0.53-0.98), and a non-significant association with overall (OR=0.97, 95% CI, 0.92-1.03) and proliferative DR (OR=0.98, 95% CI, 0.91-1.05).

CONCLUSIONS: Both observational and mendelian randomization analyses showed a significantly lower risk of DR for patients treated with GLP-1 RAs, which calls for further studies to validate these findings.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Diabetes Mellitus, Type 2/drug therapy, Hypoglycemic Agents, Diabetic Retinopathy/epidemiology, Glucagon-Like Peptide-1 Receptor/genetics, Genome-Wide Association Study, Mendelian Randomization Analysis, Glucagon-Like Peptide 1
in
BMC Medicine
volume
21
article number
40
pages
1 - 10
publisher
BioMed Central (BMC)
external identifiers
  • pmid:36737746
  • scopus:85147436345
ISSN
1741-7015
DOI
10.1186/s12916-023-02753-6
language
English
LU publication?
yes
additional info
© 2023. The Author(s).
id
b12a1037-3c3d-43ca-b715-7997f0699503
date added to LUP
2023-02-09 16:17:49
date last changed
2024-04-18 10:05:03
@article{b12a1037-3c3d-43ca-b715-7997f0699503,
  abstract     = {{<p>BACKGROUND: The ability of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to decrease certain microvascular events has called for the investigation of GLP-1 RAs against diabetic retinopathy (DR), but the evidence is limited. By combining data from observational and Mendelian randomization (MR) studies, we aimed to investigate whether GLP-1 RAs decrease the risk of DR.</p><p>METHODS: We combined data from several Swedish Registers and identified patients with incident type 2 diabetes being treated with GLP-1 RAs between 2006 and 2015, and matched them to diabetic patients who did not use GLP-1 RAs as the comparisons. The Cox proportional hazards models were applied to assess the risk of DR. We further performed the summary-data-based MR (SMR) analyses based on the Genotype-Tissue Expression databases and the Genome-Wide Association Study of DR from the FinnGen consortium.</p><p>RESULTS: A total of 2390 diabetic patients were treated with GLP-1 RAs and the incidence of DR was 5.97 per 1000 person-years. Compared with diabetic patients who did not use GLP-1 RAs having an incidence of 12.85 per 1000 person-years, the adjusted hazard ratio (HR) of DR was 0.42 [95% confidence interval (CI), 0.29-0.61]. Genetically-predicted GLP1R expression (the target of GLP-1 RAs) showed an inverse association with background [odds ratio (OR)=0.83, 95% CI, 0.71-0.97] and severe nonproliferative DR (OR=0.72, 95% CI, 0.53-0.98), and a non-significant association with overall (OR=0.97, 95% CI, 0.92-1.03) and proliferative DR (OR=0.98, 95% CI, 0.91-1.05).</p><p>CONCLUSIONS: Both observational and mendelian randomization analyses showed a significantly lower risk of DR for patients treated with GLP-1 RAs, which calls for further studies to validate these findings.</p>}},
  author       = {{Zheng, Deqiang and Li, Ning and Hou, Rui and Zhang, Xiaoyu and Wu, Lijuan and Sundquist, Jan and Sundquist, Kristina and Ji, Jianguang}},
  issn         = {{1741-7015}},
  keywords     = {{Humans; Diabetes Mellitus, Type 2/drug therapy; Hypoglycemic Agents; Diabetic Retinopathy/epidemiology; Glucagon-Like Peptide-1 Receptor/genetics; Genome-Wide Association Study; Mendelian Randomization Analysis; Glucagon-Like Peptide 1}},
  language     = {{eng}},
  month        = {{02}},
  pages        = {{1--10}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Medicine}},
  title        = {{Glucagon-like peptide-1 receptor agonists and diabetic retinopathy : nationwide cohort and Mendelian randomization studies}},
  url          = {{http://dx.doi.org/10.1186/s12916-023-02753-6}},
  doi          = {{10.1186/s12916-023-02753-6}},
  volume       = {{21}},
  year         = {{2023}},
}