Glucagon-like peptide-1 receptor agonists and diabetic retinopathy : nationwide cohort and Mendelian randomization studies
(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
- Zheng, Deqiang LU ; Li, Ning ; Hou, Rui ; Zhang, Xiaoyu ; Wu, Lijuan ; Sundquist, Jan LU ; Sundquist, Kristina LU and Ji, Jianguang LU
- organization
- publishing date
- 2023-02-03
- 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}}, }