Progression of retinopathy with glucagon-like peptide-1 receptor agonists with cardiovascular benefits in type 2 diabetes – A systematic review and meta-analysis |
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| Institution: | 1. Section of Endocrinology and Metabolism, Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, United States of America;2. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, United States of America;3. Rudolph Matas Library of the Health Sciences, Tulane University, New Orleans, LA, United States of America;4. Tulane University Office of Academic Affairs and Provost, United States of America;1. Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea;2. Department of Physiology, Keimyung University School of Medicine, Daegu, Republic of Korea;1. Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, FL, United States of America;2. Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, United States of America;1. Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, Santiago, Chile;2. Servicio de Farmacia, Hospital Clínico de la Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, Santiago, Chile;3. Escuela de Química y Farmacia, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Av. Vicuña Mackenna 4860, Macul, Chile;4. Complejo Asistencial Dr. Sótero del Río, Avenida Concha y Toro 3459, Puente Alto, Santiago, Chile;5. División de Pediatría-Programa Diabetes de niños y adolescentes, Departamento de Nutrición, Diabetes y Metabolismo, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, Santiago, Chile;1. Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark;2. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark;3. Mech-Sense, Department of Radiology, Aalborg University Hospital, Denmark;4. Steno Diabetes Center Northern Jutland, Aalborg University Hospital, Denmark;1. Steno Diabetes Center Copenhagen, Herlev, Denmark;2. Department of Medicine, Herlev-Gentofte Hospital, Copenhagen, Denmark;3. University of Copenhagen, Copenhagen, Denmark;4. Novo Nordisk A/S, Søborg, Denmark |
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| Abstract: | AimsThe effect of Glucagon-like peptide 1 receptor agonists (GLP1 RA) on diabetic retinopathy (DR) remains controversial. Previous reviews combined data from randomized clinical trials (RCTs) with or without cardiovascular (CV) benefits and did not address confounders, therefore may have generated misleading results. The study aimed to examine the effect of GLP1RA on DR in type 2 diabetes (T2DM) in RCTs with or without CV benefits and distinguish the effect by major confounders.MethodsWe conducted electronic searches of multiple databases and a manual search using references lists. We included 13 RCTs examining the effect of GLP1 RA on health outcomes/adverse events including DR or DR complications in T2DM. We performed a random-effects model meta-analysis.ResultsGLP1RA was associated with an elevated risk of rapidly worsening DR in four major RCTs with CV benefits in T2DM (OR 1.23, 95 % CI 1.05–1.44). The association between GLP1 RA and DR was significant in subgroups of RCTs with length over 52 weeks (1.2, 1.00–1.43), using placebo as a comparator (1.22, 1.05–1.42). In subgroups with patients who had T2DM ≥10 years (1.19, 0.99–1.42) or with subjects enrolled from multiple countries (1.2, 0.99–1.46), the association appeared to be evident but did not reach statistical significance.ConclusionsGLP1 RA including liraglutide, semaglutide, and dulaglutide are associated with an increased risk of rapidly worsening DR in RCTs with CV benefits. Further data from clinical studies with longer follow-up purposefully designed for DR risk assessment, particularly including patients of established DR are warranted. |
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