DPP-4 inhibitors.
Inhibition of dipeptidyl peptidase 4 (DPP-4) is a novel treatment for type-2 diabetes. DPP-4 inhibition prevents the inactivation of glucagon-like peptide 1 (GLP-1), which increases levels of active GLP-1. This increases insulin secretion and reduces glucagon secretion, thereby lowering glucose levels. Several DPP-4 inhibitors are in clinical development. Most experience so far has been with sitagliptin (Merck; approved by the FDA) and vildagliptin (Novartis; filed). These are orally active compounds with a long duration, allowing once-daily administration. Both sitagliptin and vildagliptin improve metabolic control in type-2 diabetes, both in monotherapy and in combination with metformin and thiazolidinediones. A reduction in HbA(1c) of approximately 1% is seen in studies of DPP-4 inhibition of up to 52 weeks' duration. DPP-4 inhibition is safe and well tolerated, the risk of hypoglycaemia is minimal, and DPP-4 inhibition is body-weight neutral. DPP-4 inhibition is suggested to be a first-line treatment of type-2 diabetes, particularly in its early stages in combination with metformin. However, the durability and long-term safety of DPP-4 inhibition remain to be established.
Ahrén
Bo
B
Department of Clinical Sciences, Division of Medicine, B11 BMC, SE-221 84 Lund University, Lund, Sweden. bo.ahren@med.lu.se
D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004359:Drug Therapy, Combination; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism / Q000627:therapeutic use; D000078790:Insulin Secretion; D050356:Lipid Metabolism / Q000187:drug effects; D008687:Metformin / Q000627:therapeutic use; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use; D000077205:Pioglitazone; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use; D011759:Pyrrolidines / Q000009:adverse effects / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D013379:Substrate Specificity; D045162:Thiazolidinediones / Q000627:therapeutic use; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use; D000077597:Vildagliptin
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D009570:Nitriles; D011480:Protease Inhibitors; D011719:Pyrazines; D011759:Pyrrolidines; D045162:Thiazolidinediones; D014230:Triazoles; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D008687:Metformin; D000077597:Vildagliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate; D000077205:Pioglitazone