Impact of glucose-lowering drugs on cardiovascular disease in type 2 diabetes

Eur Heart J. 2015 Sep 7;36(34):2288-96. doi: 10.1093/eurheartj/ehv239. Epub 2015 Jun 10.

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by multiple pathophysiologic abnormalities. With time, multiple glucose-lowering medications are commonly required to reduce and maintain plasma glucose concentrations within the normal range. Type 2 diabetes mellitus individuals also are at a very high risk for microvascular complications and the incidence of heart attack and stroke is increased two- to three-fold compared with non-diabetic individuals. Therefore, when selecting medications to normalize glucose levels in T2DM patients, it is important that the agent not aggravate, and ideally even improve, cardiovascular risk factors (CVRFs) and reduce cardiovascular morbidity and mortality. In this review, we examine the effect of oral (metformin, sulfonylureas, meglitinides, thiazolidinediones, DPP4 inhibitors, SGLT2 inhibitors, and α-glucosidase inhibitors) and injectable (glucagon-like peptide-1 receptor agonists and insulin) glucose-lowering drugs on established CVRFs and long-term studies of cardiovascular outcomes. Firm evidence that in T2DM cardiovascular disease can be reversed or prevented by improving glycaemic control is still incomplete and must await large, long-term clinical trials in patients at low risk using modern treatment strategies, i.e., drug combinations designed to maximize HbA1c reduction while minimizing hypoglycaemia and excessive weight gain.

Keywords: Cardiovascular disease; Cardiovascular risk; Glucose-lowering drugs; Type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Carbamates / therapeutic use
  • Clinical Trials as Topic
  • Coronary Artery Disease / drug therapy
  • Coronary Artery Disease / etiology
  • Cyclohexanes / therapeutic use
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Angiopathies / etiology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glycoside Hydrolase Inhibitors / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use
  • Metformin / therapeutic use
  • Nateglinide
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / therapeutic use
  • Piperidines / therapeutic use
  • Sodium-Glucose Transport Proteins / antagonists & inhibitors
  • Sulfonylurea Compounds / therapeutic use
  • Thiazolidinediones / therapeutic use
  • Treatment Outcome

Substances

  • Carbamates
  • Cyclohexanes
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucagon-Like Peptide-1 Receptor
  • Glycoside Hydrolase Inhibitors
  • Hypoglycemic Agents
  • Insulin
  • Piperidines
  • Sodium-Glucose Transport Proteins
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • Nateglinide
  • Phenylalanine
  • repaglinide
  • Metformin