Clinical results of treating type 2 diabetic patients with sitagliptin, vildagliptin or saxagliptin--diabetes control and potential adverse events.
Inhibition of dipeptidyl peptidase-4 (DPP-4) is a novel oral treatment for type 2 diabetes. DPP-4 inhibition increases insulin secretion and reduces glucagon secretion by preventing the inactivation of glucagon-like peptide-1 (GLP-1), thereby lowering glucose levels. Several DPP-4 inhibitors are in clinical development; more studies exist for sitagliptin and vildagliptin. They improve metabolic control in type 2 diabetes in monotherapy and also in combination with metformin, sulphonylurea and thiazolidinediones. HbA(1c) is reduced by approximately 0.6-1.1% in studies up to 52 weeks. Similar, although more limited, results were obtained for saxagliptin. DPP-4 inhibitors are safe and tolerable with no increased risk of adverse events compared to placebo and have a low risk of hypoglycaemia. DPP-4 inhibitors are body weight-neutral. The DPP-4 inhibitors are recommended for use in the early stage of type 2 diabetes, in combination with metformin in subjects with inadequate glycaemic control. DPP-4 inhibition may also be used in combination with sulphonylurea and thiazolidinediones and potentially also in combination with insulin. The durability and long-term safety of DPP-4 inhibitors remain to be established.
Ahrén
Bo
B
Department of Clinical Sciences, Lund University, Lund, Sweden. bo.ahren@med.lu.se
D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004151:Dipeptides / Q000627:therapeutic use*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007328:Insulin / Q000008:administration & dosage; D008687:Metformin / Q000008:administration & dosage; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D000077205:Pioglitazone; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000009:adverse effects / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds / Q000008:administration & dosage; D045162:Thiazolidinediones / Q000008:administration & dosage; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077597:Vildagliptin
D000218:Adamantane; D001786:Blood Glucose; D004151:Dipeptides; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007328:Insulin; D008687:Metformin; D009570:Nitriles; D000077205:Pioglitazone; D011719:Pyrazines; D011759:Pyrrolidines; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D014230:Triazoles; D000077597:Vildagliptin; C517652:hemoglobin A1c protein, human; C502994:saxagliptin