Glucagon‐like peptide‐1 (GLP‐1) receptor agonists in type 2 diabetes and long‐term complications: FOCUS on retinopathy

Marchand, Lucien; Luyton, Cédric; Bernard, A

doi:10.1111/dme.14390

Cited by 8 publications

(4 citation statements)

References 11 publications

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“…5,6,10,11,37,60 The impact of GLP-1RAs on the risk of diabetic retinopathy in humans remains unclear. 42,61 In the PIONEER and SUSTAIN phase IIIa trials, the rate of diabetic retinopathy was similar for semaglutide versus comparators, while in the SUSTAIN 6 CVOT, diabetic retinopathy complications occurred at a higher rate with semaglutide versus placebo. It is possible that the higher incidence of diabetic retinopathy in SUSTAIN 6 may have been related to substantial and rapid reductions in HbA 1c during the first 16 weeks of treatment, but the mechanisms are not fully established.…”

Section: Notementioning

confidence: 99%

Safety and tolerability of semaglutide across the SUSTAIN and PIONEER phase IIIa clinical trial programmes

Aroda

Erhan

Jelnes

et al. 2023

Diabetes Obesity Metabolism

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Aim Glucagon‐like peptide‐1 receptor agonists improve glycaemic control: some are now available as oral and subcutaneous formulations, and some have indications for reducing cardiovascular risk. The expanded scope for these therapies warrants comprehensive safety evaluations. We report the safety/tolerability of subcutaneous and oral semaglutide from the SUSTAIN and PIONEER clinical trial programmes, respectively. Materials and methods Adverse events (AEs) from 16 randomized placebo‐ or active‐controlled phase IIIa trials in patients with type 2 diabetes (n = 11 159) including once‐weekly subcutaneous semaglutide (n = 3150; SUSTAIN trials) or once‐daily oral semaglutide (n = 4116; PIONEER trials) were analysed. Data pools were analysed for each programme, with separate analyses of cardiovascular outcomes trials (CVOTs; n = 6480). Results In the phase IIIa pools, gastrointestinal disorders were reported in 41.9%/39.1% of patients with subcutaneous/oral semaglutide, respectively (most prevalent during initiation/escalation) versus 22.0%/24.8% with comparators. Rates of kidney disorders, acute pancreatitis, malignant neoplasms, hypoglycaemia, diabetic retinopathy, heart failure and other cardiovascular events were similar for semaglutide versus comparators. Cholelithiasis incidence was higher with subcutaneous and oral semaglutide versus placebo. Diabetic retinopathy incidence was higher with subcutaneous semaglutide versus placebo in SUSTAIN 6. Small pulse rate increases occurred with both formulations; there was no increased rate of arrhythmias. Fatal AE incidence was similar between semaglutide and comparators. Versus placebo, CVOTs showed a reduced risk of major adverse cardiovascular events with subcutaneous semaglutide and non‐inferiority criteria were met with oral semaglutide. Conclusions The most common AEs with semaglutide were gastrointestinal disorders, which decreased with continued therapy. These comprehensive safety/tolerability data may better inform patient selection and guidance in care.

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Section: Notementioning

confidence: 99%

Safety and tolerability of semaglutide across the SUSTAIN and PIONEER phase IIIa clinical trial programmes

Aroda

Erhan

Jelnes

et al. 2023

Diabetes Obesity Metabolism

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“…For GLP-1 RAs, worsening of retinopathy has been considered a new potential side effect of this treatment. An unexpected increase in retinopathy was found in SUSTAIN-6, and a nonsignificantly higher rate of DR was found in LEADER and REWIND ( 45 ). However, poor outcomes, such as blindness or the need for numerous procedures, which damage a person’s quality of life and raise expenditures, were not adequately described, and definitions of ocular events varied widely among these studies.…”

Section: Discussionmentioning

confidence: 90%

Predictive model for diabetic retinopathy under limited medical resources: A multicenter diagnostic study

Yang¹,

Tan²,

He³

et al. 2023

Front. Endocrinol.

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BackgroundComprehensive eye examinations for diabetic retinopathy is poorly implemented in medically underserved areas. There is a critical need for a widely available and economical tool to aid patient selection for priority retinal screening. We investigated the possibility of a predictive model for retinopathy identification using simple parameters.MethodsClinical data were retrospectively collected from 4, 159 patients with diabetes admitted to five tertiary hospitals. Independent predictors were identified by univariate analysis and least absolute shrinkage and selection operator (LASSO) regression, and a nomogram was developed based on a multivariate logistic regression model. The validity and clinical practicality of this nomogram were assessed using concordance index (C-index), area under the receiver operating characteristic curve (AUROC), calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC).ResultsThe predictive factors in the multivariate model included the duration of diabetes, history of hypertension, and cardiovascular disease. The three-variable model displayed medium prediction ability with an AUROC of 0.722 (95%CI 0.696-0.748) in the training set, 0.715 (95%CI 0.670-0.754) in the internal set, and 0.703 (95%CI 0.552-0.853) in the external dataset. DCA showed that the threshold probability of DR in diabetic patients was 17-55% according to the nomogram, and CIC also showed that the nomogram could be applied clinically if the risk threshold exceeded 30%. An operation interface on a webpage (https://cqmuxss.shinyapps.io/dr_tjj/) was built to improve the clinical utility of the nomogram.ConclusionsThe predictive model developed based on a minimal amount of clinical data available to diabetic patients with restricted medical resources could help primary healthcare practitioners promptly identify potential retinopathy.

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“…An experimental study demonstrated that the application of GLP-1RA can mitigate neurodegeneration in the retina [11]. GLP-1RA is associated with a reduction in the incidence of diabetic retinopathy as well as a decrease in retinal vascular leakage and damage to the blood-retinal barrier [12,13]. However, another study reported a nonsignificant association between the use of GLP-1RA and retinal angiogenesis [10].…”

Section: Ivyspringmentioning

confidence: 99%

Prescription of glucagon-like peptide 1 agonists and risk of subsequent open-angle glaucoma in individuals with type 2 diabetes mellitus

Chuang,

Wang,

Chang

et al. 2024

Int. J. Med. Sci.

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Background:The glucagon-like peptide 1 receptor agonist (GLP-1RA) is an antidiabetic medication with vascular protection and anti-inflammatory properties. Theoretically, the use of GLP-1RA should inhibit the development of open-angle glaucoma (OAG) as both vascular damage and inflammation are associated with OAG. Therefore, our objective was to investigate the association between the application of GLP-1RA and the subsequent OAG in individuals with type 2 diabetes mellitus (T2DM). Methods: We conducted a retrospective cohort study by using data from the National Health Insurance Research Database (NHIRD) of Taiwan. Participants with T2DM were divided into those who used GLP-1RA and those who did not, forming the GLP-1RA and control groups. The primary outcome was the occurrence of OAG based on diagnostic codes. Cox proportional hazard regression was employed to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for OAG. Results: 91 patients in the control group developed OAG, and 40 patients in the GLP-1RA group developed OAG. After adjustment for all covariates, the GLP-1RA group exhibited a significantly lower incidence of OAG compared with the control group (aHR: 0.712, 95% CI: 0.533-0.936. P = 0.0025). In the subgroup analyses, the association between GLP-1RA use and OAG incidence was more pronounced in patients with T2DM using GLP-1RA and aged younger than 60 years (P = 0.0438). Conclusion:The prescription of GLP-1RA is associated with a lower incidence of subsequent OAG in individuals with T2DM, and this association was more significant in patients with T2DM under the age of 60 years.

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Glucagon‐like peptide‐1 (GLP‐1) receptor agonists in type 2 diabetes and long‐term complications: FOCUS on retinopathy

Cited by 8 publications

References 11 publications

Safety and tolerability of semaglutide across the SUSTAIN and PIONEER phase IIIa clinical trial programmes

Safety and tolerability of semaglutide across the SUSTAIN and PIONEER phase IIIa clinical trial programmes

Predictive model for diabetic retinopathy under limited medical resources: A multicenter diagnostic study

Prescription of glucagon-like peptide 1 agonists and risk of subsequent open-angle glaucoma in individuals with type 2 diabetes mellitus

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