Beyond the Glycaemic Control of Dapagliflozin: Microangiopathy and Non-classical Complications

Abstract

Dapagliflozin is a selective sodium-glucose cotransporter 2 inhibitor (SGLT2i) indicated for the treatment of type 2 diabetes mellitus (T2DM), heart failure (HF) with reduced ejection fraction (EF) and chronic kidney disease (CKD). In monotherapy or as an additive therapy, dapagliflozin aids glycaemic control, is associated with reductions in blood pressure and weight, and promotes a favourable lipid profile. In this review, we address the impact of dapagliflozin on cardiovascular risk factors and common microangiopathic complications such as kidney disease and retinopathy in patients with T2DM. Furthermore, we evaluate its potential beneficial effects on other less frequent complications of diabetes, such as macular oedema, cognitive impairment, non-alcoholic fatty liver disease and respiratory disorders during sleep. Moreover, the underuse of SGLT2i in clinical practice is discussed. Our goal is to help translate this evidence into clinical practice.

Dapagliflozin Treatment Augments Bioactive Phosphatidylethanolamine Concentrations in Kidney Cortex Membrane Fractions of Hypertensive Diabetic db/db Mice and Alters the Density of Lipid Rafts in Mouse Proximal Tubule Cells

“…Mechanistically, SGLT2 inhibitors including dapagliflozin can reduce the maximum carrying capacity of tubular glucose absorption, which raises urine glucose excretion and lowers plasma glucose levels. In addition to their hypoglycemic actions, SGLT2 inhibitors have been demonstrated to offer blood pressure lower effects [ 3 , 4 , 5 ], weight-loss [ 6 , 7 ], and cardioprotective benefits [ 6 , 8 , 9 ] and to enhance glucose metabolism in epicardial fat [ 10 ]. Furthermore, dapagliflozin may improve lipoprotein profile and atherosclerosis development [ 11 ], in contrast to empagliflozin that raises low-density lipoprotein cholesterol levels [ 12 ].…”

Prevalence of self-reported visual impairment among people in Canada with and without diabetes: findings from population-based surveys from 1994 to 2014

“…30 Using Canadian data, we report that visual impairment prevalence decreased among people with and without diabetes from 1994 to 2014, irrespective of their level of education and income. The decreased visual impairment prevalence likely reflects the collective efforts by clinicians, researchers, the public and government to prevent vision loss, including better understanding of diabetic eye diseases, [31][32][33] better bloodglucose control, [34][35][36][37][38] recent effective treatment for advanced diabetic retinopathy and technology (e.g., optical coherence tomography) for early detection of diabetic retinal pathologies, [39][40][41][42][43][44] government coverage for new advancements and various initiatives for increased diabetic eye screening. [45][46][47] Our results are also in accordance with studies that reported a significantly higher visual impairment prevalence among people with diabetes than those without.…”

Risk of Diabetic Retinopathy in Patients With Type 2 Diabetes After SGLT‐2 Inhibitors: A Nationwide Population Cohort Study

“…Shih-Ting Huang 1,2,3, † , Pei-Jane Bair 3,4, † , Shih-Sheng Chang 3,5 , Yu-Nong Kao 1,3 , San-Ni Chen 6 , I-Kang Wang 3,4 , Chih-Wei Chiu 1 , Chi-Tzung Chang 3 , Ying-Hsiu Shih 7 , Chi-Yuan Li 4 and Tung-Min Yu 1,3,4, * Diabetic retinopathy (DR) accounts for 80% of cases of vision loss in patients with type 2 diabetes mellitus (T2DM). Interventional treatments are only indicated in advanced DR and are ineffective in some patients.…”

“…In addition to remarkable effect of cardiorenal protection, SGLT2is have been considered having additional benefits in various diabetic complications, such as macular edema, cognitive impairment, and nonalcoholic fatty liver disease. 6 SGLT2is and dipeptidyl peptidase-4 inhibitors (DPP4is) are both recommended as second-line, add-on oral hypoglycemia medications in uncomplicated patients with diabetes. 7 A meta-analysis comparing the efficacy and safety of SGLT2is and DPP4is revealed that SGLT2is plus metformin was associated with a more significant decrease in fasting plasma glucose than was DPP4is plus metformin.…”

“…Instead of stimulating insulin release, SGLT2is improve β‐cell function by improving glucotoxicity, alleviating insulin resistance, and increasing insulin sensitivity. In addition to remarkable effect of cardiorenal protection, SGLT2is have been considered having additional benefits in various diabetic complications, such as macular edema, cognitive impairment, and nonalcoholic fatty liver disease 6 …”