Pharmacology and Therapeutic Implications of Current Drugs for Type 2 Diabetes Mellitus

Nat Rev Endocrinol. 2016 Oct;12(10):566-92. doi: 10.1038/nrendo.2016.86. Epub 2016 Jun 24.

Abstract

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies.

Publication types

  • Review

MeSH terms

  • Benzamides / pharmacology
  • Benzamides / therapeutic use
  • Biguanides / pharmacology
  • Biguanides / therapeutic use
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Drug Therapy, Combination
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glycoside Hydrolase Inhibitors / pharmacology
  • Glycoside Hydrolase Inhibitors / therapeutic use
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / pharmacology
  • Insulin / therapeutic use
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sulfonylurea Compounds / pharmacology
  • Sulfonylurea Compounds / therapeutic use
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use

Substances

  • Benzamides
  • Biguanides
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucagon-Like Peptide-1 Receptor
  • Glycoside Hydrolase Inhibitors
  • Hypoglycemic Agents
  • Insulin
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • meglitinide