Abstract
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a relatively novel class of drug for treating type 2 diabetes mellitus (T2DM) that inhibits glucose reabsorption in the renal proximal tubule to promote glycosuria and reduce blood glucose levels. SGLT2i has been clinically indicated for treating T2DM, with numerous recent publications focussing on both primary and secondary prevention of cardiovascular and renal events in Type 2 diabetic patients. The most recent clinical trials showed that SGLT2i have moderately significant beneficial effects on atherosclerotic major adverse cardiovascular events (MACE) in patients with histories of atherosclerotic cardiovascular disease. In this review and analysis, SGLT2i have however demonstrated clinically significant benefits in reducing hospitalisation for heart failure and worsening of chronic kidney disease (CKD) irrespective of pre-existing atherosclerotic cardiovascular disease or previous heart failure history. A meta-analysis suggests that all SGLT2 inhibitors demonstrated the therapeutic benefit on all-cause and cardiovascular mortality, as shown in EMPAREG OUTCOME study with a significant decrease in myocardial infarction, without increased stroke risk. All the above clinical trial recruited type 2 diabetic patients. This article aims to postulate and review the possible primary prevention role of SGLT2i in healthy individuals by reviewing the current literature and provide a prospective overview. The emphasis will include primary prevention of Type 2 Diabetes, Heart Failure, CKD, Hypertension, Obesity and Dyslipidaemia in healthy individuals, whom are defined as healthy, low or intermediate risks patients.
Highlights
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) is a novel class of medication that decreases plasma glucose concentration
The use of SGLT2i is recommended to combine with metformin in treating type 2 diabetes mellitus (T2DM) patients, as well as considered use in diabetic patients with cardiovascular diseases or at least two cardiovascular risk factors [7]
SGLT2i are currently recommended in China as an additional therapy in patients who are unable to achieve glycaemic control with metformin monotherapy [11, 12]
Summary
SGLT2i is a novel class of medication that decreases plasma glucose concentration. Diabetic patients’ glomerular filtration of glucose increased significantly to 180–240g daily above renal glucose threshold, leading to glycosuria. SGLT2i bind to SGLT2 receptors with an insulin-independent mechanism of action, further increasing glycosuria and lowering plasma glucose concentration [1], leading to cardiovascular and renal benefit demonstrated in systematic review and meta-analysis [1, 2]. There is currently no global consensus guideline for the indication of SGLT2i use in different regions and countries. We reviewed guidelines and recommendations for SGLT2i use in countries with a large population of type 2 diabetes (Table 1) in this narrative review aiming to address whether a future RCT is needed to examine the potential primary preventive role of SGLT2i in healthy individual
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