Drugs for Diabetes: Part 8 SGLT2 Inhibitors

Alison MacEwen; Gerard A McKay; Miles Fisher

Disclosures

Br J Cardiol. 2012;19(1):26-29. 

In This Article

Abstract and Introduction

Abstract

SGLT2 inhibitors are a new class of oral drugs for the treatment of type 2 diabetes mellitus currently in phase III studies. They inhibit glucose re-absorption in the proximal renal tubules providing an insulin independent mechanism to lower blood glucose. Their use in clinical practice is associated with improved glycaemic control, weight loss and a low risk of hypoglycaemia. Phase III cardiovascular safety studies are ongoing.

Introduction

Type 2 diabetes mellitus is a major risk factor for developing both microvascular (retinopathy, nephropathy and neuropathy) and macrovascular complications (coronary heart disease, cerebrovascular disease and peripheral vascular disease).[1] The link between maintaining good glycaemic control and prevention of these complications is well established.[2–4] Guidelines recommend a target glycosylated haemoglobin (HbA1c) of 7% or less, but a large number of patients fail to meet this target and, as of yet, no ideal pharmacological blood glucose-lowering agent exists.

Existing pharmacological therapies, which have been previously described in this series, are focused on reducing insulin resistance, increasing insulin secretion, slowing carbohydrate digestion, restraining glucagon production, and supplying exogenous insulin. Treatment with traditional glucose-lowering therapies, including metformin, sulphonylureas and insulin, is commonly limited by gastrointestinal side effects, weight gain and hypoglycaemia.[2,3] Treatment with thiazolidinediones has been associated with cardiovascular safety concerns, weight gain, increased fracture risk and fluid retention.[5,6] Dipeptidylpeptidase-4 (DPP-4) inhibitors are well tolerated, but are merely weight neutral. Glucagon-like peptide-1 (GLP-1) analogues result in moderate weight loss, but they need to be injected and their use is limited by gastrointestinal side effects.[7] The increasing prevalence of type 2 diabetes, in combination with limitations of current therapies, has led to the search for newer alternatives. SGLT2 inhibitors represent a novel 'glucuretic' therapeutic strategy for the treatment of type 2 diabetes, and are currently in phase III trials.

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