Comparing and Contrasting the Effects of the SGLT Inhibitors Canagliflozin and Empagliflozin on the Progression of Retinopathy
Background: Diabetic retinopathy (DR) is a leading cause of end-stage blindness globally and is arguably one of the most disabling complications of both Type 1 and Type 2 diabetes. Sodium Glucose Cotransporter-2 (SGLT2) inhibitors have now been successfully introduced to clinical medicine and exert...
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| Format: | Article |
| Language: | English |
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IMR Press
2023-04-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/28/4/10.31083/j.fbl2804083 |
| _version_ | 1797837646596145152 |
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| author | Lakshini Y. Herat Jennifer R. Matthews Elizabeth P. Rakoczy Markus P. Schlaich Vance B. Matthews |
| author_facet | Lakshini Y. Herat Jennifer R. Matthews Elizabeth P. Rakoczy Markus P. Schlaich Vance B. Matthews |
| author_sort | Lakshini Y. Herat |
| collection | DOAJ |
| description | Background: Diabetic retinopathy (DR) is a leading cause of end-stage blindness globally and is arguably one of the most disabling complications of both Type 1 and Type 2 diabetes. Sodium Glucose Cotransporter-2 (SGLT2) inhibitors have now been successfully introduced to clinical medicine and exert multiple beneficial effects in diabetic patients. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may alleviate the progression of DR. Therefore, we aimed to compare the effectiveness of two clinically available SGLT2 inhibitors, Empagliflozin and Canagliflozin, on the progression of Retinopathy and DR using well-characterised mouse models, Kimba and Akimba, respectively. Methods: Empagliflozin, Canagliflozin (25 mg/kg/day) or vehicle was administered to 10-week-old mice via drinking water for 8-weeks. Urine glucose levels were measured to ascertain SGLT2 inhibition promoted glucose excretion. Weekly body weight and water intake measurements were obtained. After 8-weeks of treatment, body weight, daily water intake, fasting blood glucose levels were measured and eye tissue was harvested. The retinal vasculature was assessed using immunofluorescence. Results: Empagliflozin treated Akimba mice exhibited metabolic benefits suggested by healthy body weight gain and significantly reduced fasting blood glucose levels. Treatment with Empagliflozin reduced retinal vascular lesions in both Kimba and Akimba mice. Canagliflozin improved body weight gain, reduced blood glucose levels in Akimba mice, and reduced the development of retinal vascular lesions in Kimba mice. Conclusions: Our data demonstrates that Empagliflozin has future potential as a therapeutic for Retinopathy and DR and should now be considered for human trials. |
| first_indexed | 2024-04-09T15:29:09Z |
| format | Article |
| id | doaj.art-88c7e1d63b104a7b93e23f04c3a0326a |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-04-09T15:29:09Z |
| publishDate | 2023-04-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-88c7e1d63b104a7b93e23f04c3a0326a2023-04-28T09:24:06ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-04-012848310.31083/j.fbl2804083S2768-6701(23)00859-6Comparing and Contrasting the Effects of the SGLT Inhibitors Canagliflozin and Empagliflozin on the Progression of RetinopathyLakshini Y. Herat0Jennifer R. Matthews1Elizabeth P. Rakoczy2Markus P. Schlaich3Vance B. Matthews4Dobney Hypertension Centre, School of Biomedical Sciences – Royal Perth Hospital Unit, University of Western Australia, Crawley, WA 6009, AustraliaDobney Hypertension Centre, School of Biomedical Sciences – Royal Perth Hospital Unit, University of Western Australia, Crawley, WA 6009, AustraliaDepartment of Molecular Ophthalmology, University of Western Australia, Crawley, WA 6009, AustraliaDobney Hypertension Centre, Medical School – Royal Perth Hospital Unit, University of Western Australia, Crawley, WA 6009, AustraliaDobney Hypertension Centre, School of Biomedical Sciences – Royal Perth Hospital Unit, University of Western Australia, Crawley, WA 6009, AustraliaBackground: Diabetic retinopathy (DR) is a leading cause of end-stage blindness globally and is arguably one of the most disabling complications of both Type 1 and Type 2 diabetes. Sodium Glucose Cotransporter-2 (SGLT2) inhibitors have now been successfully introduced to clinical medicine and exert multiple beneficial effects in diabetic patients. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may alleviate the progression of DR. Therefore, we aimed to compare the effectiveness of two clinically available SGLT2 inhibitors, Empagliflozin and Canagliflozin, on the progression of Retinopathy and DR using well-characterised mouse models, Kimba and Akimba, respectively. Methods: Empagliflozin, Canagliflozin (25 mg/kg/day) or vehicle was administered to 10-week-old mice via drinking water for 8-weeks. Urine glucose levels were measured to ascertain SGLT2 inhibition promoted glucose excretion. Weekly body weight and water intake measurements were obtained. After 8-weeks of treatment, body weight, daily water intake, fasting blood glucose levels were measured and eye tissue was harvested. The retinal vasculature was assessed using immunofluorescence. Results: Empagliflozin treated Akimba mice exhibited metabolic benefits suggested by healthy body weight gain and significantly reduced fasting blood glucose levels. Treatment with Empagliflozin reduced retinal vascular lesions in both Kimba and Akimba mice. Canagliflozin improved body weight gain, reduced blood glucose levels in Akimba mice, and reduced the development of retinal vascular lesions in Kimba mice. Conclusions: Our data demonstrates that Empagliflozin has future potential as a therapeutic for Retinopathy and DR and should now be considered for human trials.https://www.imrpress.com/journal/FBL/28/4/10.31083/j.fbl2804083diabetic retinopathydiabetesakimbakimbamouse modelssodium glucose cotransporterssglt2 inhibitorsempagliflozincanagliflozinretinal vasculature |
| spellingShingle | Lakshini Y. Herat Jennifer R. Matthews Elizabeth P. Rakoczy Markus P. Schlaich Vance B. Matthews Comparing and Contrasting the Effects of the SGLT Inhibitors Canagliflozin and Empagliflozin on the Progression of Retinopathy Frontiers in Bioscience-Landmark diabetic retinopathy diabetes akimba kimba mouse models sodium glucose cotransporters sglt2 inhibitors empagliflozin canagliflozin retinal vasculature |
| title | Comparing and Contrasting the Effects of the SGLT Inhibitors Canagliflozin and Empagliflozin on the Progression of Retinopathy |
| title_full | Comparing and Contrasting the Effects of the SGLT Inhibitors Canagliflozin and Empagliflozin on the Progression of Retinopathy |
| title_fullStr | Comparing and Contrasting the Effects of the SGLT Inhibitors Canagliflozin and Empagliflozin on the Progression of Retinopathy |
| title_full_unstemmed | Comparing and Contrasting the Effects of the SGLT Inhibitors Canagliflozin and Empagliflozin on the Progression of Retinopathy |
| title_short | Comparing and Contrasting the Effects of the SGLT Inhibitors Canagliflozin and Empagliflozin on the Progression of Retinopathy |
| title_sort | comparing and contrasting the effects of the sglt inhibitors canagliflozin and empagliflozin on the progression of retinopathy |
| topic | diabetic retinopathy diabetes akimba kimba mouse models sodium glucose cotransporters sglt2 inhibitors empagliflozin canagliflozin retinal vasculature |
| url | https://www.imrpress.com/journal/FBL/28/4/10.31083/j.fbl2804083 |
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