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Study 4 of 9Setmelanotide literatureDiabetes, obesity & metabolism · ObservationalHigh-impact journal2023

Risk of Age-Related Ocular Diseases in Non-Diabetic Adults With Obesity Using Glucagon-Like Peptide 1 Receptor Agonists.

GLP-1 receptor agonists may be linked to lower risks of age-related eye diseases in older adults with obesity, but further research is needed to confirm these findings.

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Where it sits

this study against the rest of the setmelanotide corpus
1
Preclinical
6
Observational · this one
0
Open-label
1
Randomised
1
Reviews

Summary and findings

This study assessed the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) with the incidence of age-related ocular diseases in non-diabetic older adults with obesity. A total of 68,536 patients were included, with 34,268 in each group, and significant reductions in ocular disease risks were reported. No therapeutic claims are made.

How much of this paper we could read: full text read (0.80). We had a clear abstract, so the summary below closely tracks the paper. What this means →
RR: 0.45; 95% CI, 0.40-0.50 for cataract risk at 5 years.n=685362023

Abstract

The authors’ words, as Diabetes, obesity & metabolism supplied them

<h4>Aims</h4>To assess whether glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with a lower incidence of age-related ocular diseases in non-diabetic older adults with overweight or obesity.<h4>Materials and methods</h4>We conducted a retrospective, propensity score-matched cohort study using the TriNetX global research network. Non-diabetic, overweight or obese adults aged ≥ 60 years with an ophthalmic disease-naïve baseline were enrolled. Patients receiving liraglutide or semaglutide were matched 1:1 with users of alternative weight-loss medications (bupropion-naltrexone, phentermine-topiramate, setmelanotide or orlistat). Outcomes included up to 5-year risks of incident cataract, age-related macular degeneration (AMD), ocular hypertension, primary open-angle glaucoma (POAG) and dry eye syndrome (DES).<h4>Results</h4>After matching, 68 536 patients were included (34 268 per group). GLP-1RAs use was significantly associated with a lower 5-year risk of cataract (RR: 0.45; 95% CI, 0.40-0.50), AMD (RR: 0.33; 95% CI, 0.23-0.48), ocular hypertension (RR: 0.56; 95% CI, 0.34-0.91), POAG (RR: 0.50; 95% CI, 0.32-0.78) and DES (RR: 0.36; 95% CI, 0.31-0.42). Sensitivity analyses consistently demonstrated a lower risk across cataract subtypes, including nuclear (RR: 0.42; 95% CI, 0.37-0.48), cortical (RR: 0.37; 95% CI, 0.36-0.55) and posterior subcapsular cataracts (RR: 0.48; 95% CI, 0.26-0.91). Similar reductions were observed in retinal haemorrhage or edema (RR: 0.44; 95% CI, 0.30-0.63) and the use of dry eye-related medication (RR: 0.44; 95% CI, 0.39-0.50).<h4>Conclusions</h4>GLP-1RAs were associated with lower risks of multiple age-related ocular conditions in non-diabetic older adults.

Background

This paper investigates the potential impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on the incidence of age-related ocular diseases in non-diabetic older adults with obesity. Prior studies have suggested that GLP-1RAs may have benefits beyond glycemic control, but their effects on ocular health are not well established. This study aims to fill that gap by analyzing a large cohort of patients.

Methods

The study utilized a retrospective, propensity score-matched cohort design, analyzing data from the TriNetX global research network. The population included non-diabetic, overweight or obese adults aged ≥ 60 years, with a baseline free of ophthalmic diseases. Patients receiving liraglutide or semaglutide were matched 1:1 with users of alternative weight-loss medications, totaling 68,536 participants (n=34,268 per group). Outcomes measured included the 5-year risks of cataract, age-related macular degeneration (AMD), ocular hypertension, primary open-angle glaucoma (POAG), and dry eye syndrome (DES).

Results

The primary endpoint indicated that GLP-1RAs were associated with a lower 5-year risk of cataract (RR: 0.45; 95% CI, 0.40-0.50). Additional findings included significant reductions in the risks of AMD (RR: 0.33; 95% CI, 0.23-0.48), ocular hypertension (RR: 0.56; 95% CI, 0.34-0.91), POAG (RR: 0.50; 95% CI, 0.32-0.78), and DES (RR: 0.36; 95% CI, 0.31-0.42). Sensitivity analyses revealed consistent lower risks across various cataract subtypes.

Interpretation

The findings suggest that GLP-1RAs may be associated with a reduced risk of several age-related ocular diseases, which is a novel area of investigation. However, while the statistical significance of the results is clear, the clinical relevance of these risk reductions should be carefully considered, particularly given the observational nature of the study and potential confounding factors. The reliance on matched cohorts may not fully account for all variables affecting ocular health.

Key findings

  • RR: 0.45; 95% CI, 0.40-0.50 for cataract risk at 5 years.
  • RR: 0.33; 95% CI, 0.23-0.48 for age-related macular degeneration at 5 years.
  • RR: 0.56; 95% CI, 0.34-0.91 for ocular hypertension at 5 years.
  • RR: 0.50; 95% CI, 0.32-0.78 for primary open-angle glaucoma at 5 years.
  • RR: 0.36; 95% CI, 0.31-0.42 for dry eye syndrome at 5 years.

Limitations

  • Retrospective study design.
  • Matched cohort may introduce confounding factors.
  • Observational data, not randomized controlled trials.
  • Potential for unmeasured confounding variables.
  • Single-site data from TriNetX network.

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