To review the pharmacology, pharmacokinetics, clinical efficacy and safety studies, adverse effects, drug interactions, dosage, and administration of vildagliptin (LAF 237), a dipeptidyl peptidase IV (DPP-4) inhibitor in Phase III development for the treatment of type 2 diabetes mellitus.
Data Sources:
Information was obtained from MEDLINE searches of the English-language literature (1990–September 2005). Search terms included vildagliptin, LAF 237, DPP-IV inhibitor, DPP-4 inhibitor, and GLP-1 agonist.
Study Selection and Data Extraction:
Available literature reviewed included abstracts, clinical trials with human and animal data, and review articles.
Data Synthesis:
Vildagliptin is a potent and highly selective DPP-4 inhibitor. This novel treatment modality enhances the activity of incretin hormones through inhibition of the enzyme responsible for their degradation.
Conclusions:
Vildagliptin demonstrates good tolerability with minimal adverse effects and can effectively improve metabolic control of glucose through an array of mechanisms.
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References
1.
NauckMAKleineNOrskovCHolstJJWillmsBCreutzfeldtW. Normalization of fasting hyperglycemia by exogenous glucagons-like peptide 1 (7–36 amide) in type 2 (non-insulin dependent) diabetic patients. Diabetologia1993; 36: 741–4.
2.
MokdadAHFordESBowmanBA, Diabetes trends in the US: 1990–1998. Diabetes Care2000; 23: 1278–83.
3.
Diabetes Research Working Group. Summary of the report and recommendations of the congressionally-established Diabetes Research Working Group: a strategic plan for the 21st century. 1999. www.jdfcure.org/drwg/ (accessed 2003 Sept 10).
4.
MitznerL. Selecting the best medication for type 2 diabetes. Cortlandt Forum2003; 16 (8): 16–9.
5.
NauckMStockmannFEbertRCreutzfeldtW. Reduced incretin effect in type 2 (non-insulin dependent) diabetes. Diabetologia1986; 29: 46–52.
6.
VilsbollTHolstJJ. Incretins, insulin secretion and type 2 diabetes mellitus. Diabetologia2004; 47: 357–66.
7.
NauckMABallerBMeierJJ. Gastric inhibitory polypeptide and glucagon-like peptide-1 in the pathogeneses of type 2 diabetes. Diabetes2004; 53 (suppl 3): 190–6.
AhrenBLandin-OlssonMJanssonPASvenssonMHolmesDSchweizerA. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab2004; 89: 2078–84.
10.
HolstJJ. Therapy of type 2 diabetes mellitus based on the actions of glucagon-like peptide-1. Diabetes Metab Res Rev2002; 18: 430–41.
11.
EganJMBulottaAHuiHPerfettiR. GLP-1 receptor agonists are growth and differentiation factors for pancreatic islet β-cells. Diabetes Metab Res Rev2003; 19: 115–23.
12.
CherringtonADStevensonRWSteinerKE, Insulin, glucagon, and glucose as regulators of hepatic glucose uptake and production in vivo. Diabetes Metab Res Rev1987; 3: 307–32.
13.
ShahPVellaABasuABasuRSchwenkWFRizzaRA. Lack of suppression of glucagon contributes to postprandial hyperglycemia in subjects with type 2 diabetes mellitus. J Clin Endocrinol Metab2000; 85: 4053–9.
14.
AhrenBLarssonH. Impaired glucose tolerance (IGT) is associated with reduced insulin-induced suppression of glucagon concentrations. Diabetologia2001; 44: 1998–2003.
15.
MentleinR. Dipeptidyl-peptidase IV (CD26)—role in the inactivation of regulatory peptides. Regul Pept1999; 85: 9–24.
16.
DeaconCFJohnsenAHHolstJJ. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab1995; 80: 952–7.
17.
HolstJJDeaconCF. Inhibition of the activity of dipeptidyl peptidase IV as a treatment for type 2 diabetes. Diabetes1998; 47: 1663–70.
18.
XuGStoffersDAHabenerJFBonner-WeirS. Exendin-4 stimulates both β-cell replication and neogenesis, resulting in increased β-cell mass and improved glucose tolerance in diabetic rats. Diabetes1999; 48: 2270–6.
19.
TourrelCBailbeDLacorneMMeileMJKergoatMPorthaB. Persistent improvement of type 2 diabetes in the Goto–Kakizaki rat model by expansion of the beta-cell mass during the prediabetic period with glucagon-like peptide-1 or exendin-4. Diabetes2002; 51: 1443–52.
20.
AhrenBGomisRStandlEMillsDSchweizerA. Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care2004; 27: 2874–80.
21.
AhrenBOGomisREberhardSMillsDSchweizerA.Prolonged efficacy of LAF 237 in patients with type 2 diabetes mellitus (T2DM) inadequately treated with metformin. Presented at: American Diabetes Association 64th Annual Scientific Sessions, 2004. Orlando, FL.
22.
VillhauerEBBrinkmanJANaderiGB, 1-[[(3-hydroxy-1-adamantyl) amino] acetyl]-2-cyano-(S)-pyrrolidine: A potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J Med Chem2003; 46: 2774–89.
