Emerging role of dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes.
BACKGROUND
In type 2 diabetes mellitus (T2DM) there is a progressive loss of beta-cell function. One new approach yielding promising results is the use of the orally active dipeptidyl peptidase-4 (DPP-4) inhibitors. However, every new compound for T2DM has to prove long-term safety especially on cardiovascular outcomes.


OBJECTIVE
Systematic review and meta-analysis of the effects of sitagliptin and vildagliptin therapy on main efficacy parameters and safety. SELECTION CRITERIA, DATA COLLECTION, AND ANALYSIS: Randomized controlled clinical studies of at least 12 weeks' duration in T2DM.


RESULTS
DPP-4 inhibitors versus placebo showed glycosylated hemoglobin A1c (A1c) improvements of 0.7% versus placebo but not compared to monotherapy with other hypoglycemic agents (0.3% in favor of controls). The overall risk profile of DPP-4 inhibitors was low, however a 34% relative risk increase (95% confidence interval 10% to 64%, P = 0.004) was noted for all-cause infection associated with sitagliptin use. No data on immune function, health-related quality of life and diabetic complications could be extracted.


CONCLUSIONS
DPP-4 inhibitors have some theoretical advantages over existing therapies with oral antidiabetic compounds but should currently be restricted to individual patients. Long-term data on cardiovascular outcomes and safety are needed before widespread use of these new agents.
Richter
Bernd
B
Cochrane Metabolic and Endocrine Disorders Group, Department of General Practice, Heinrich-Heine University Duesseldorf, Duesseldorf, Germany. richterb@uni-duesseldorf.de
Bandeira-Echtler
Elizabeth
E
Bergerhoff
Karla
K
Lerch
Christian
C
D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009570:Nitriles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011719:Pyrazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077597:Vildagliptin
D000218:Adamantane; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D009570:Nitriles; D011719:Pyrazines; D011759:Pyrrolidines; D000068900:Sitagliptin Phosphate; D014230:Triazoles; D000077597:Vildagliptin; C517652:hemoglobin A1c protein, human; C042807:DPP4 protein, human