International Diabetes Federation. Diabetes Atlas. 3rd edition. Brussels, Belgium: International Diabetes Federation; 2006.
Google Scholar
Schulze MB, Hu FB. Primary prevention of diabetes: what can be done and how much can be prevented? Annu Rev Public Health. 2005;26:445–467.
PubMed
Article
Google Scholar
Fox KM, Gerber Pharmd RA, Bolinder B, Chen J, Kumar S. Prevalence of inadequate glycemic control among patients with type 2 diabetes in the United Kingdom general practice research database: a series of retrospective analyses of data from 1998 through 2002. Clin Ther, 2006;28:388–395.
PubMed
Article
Google Scholar
Yurgin N, Secnik K, Lage MJ. Antidiabetic prescriptions and glycemic control in German patients with type 2 diabetes mellitus: a retrospective database study. Clin. Ther. 2007;29:316–325.
PubMed
Article
CAS
Google Scholar
Del Prato S, Felton AM, Munro N, et al. Improving glucose management: ten steps to get more patients with type 2 diabetes to glycaemic goal. Recommendations from the Global Partnership for Effective Diabetes Management. Int J Clin Pract. 2005;59:1345–1355.
PubMed
Article
Google Scholar
National Institute for Health and Clinical Excellence (NICE). Type 2 diabetes: the management of type 2 diabetes (update). Available at: www.nice.org.uk/CG66. Accessed December 2008.
Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193–203.
PubMed
Article
CAS
Google Scholar
Brown JB, Nichols GA, Perry A. The burden of treatment failure in type 2 diabetes. Diabetes Care, 2004;27:1535–1540.
PubMed
Article
Google Scholar
UK Prospective Diabetes Study Group. United Kingdom Prospective Diabetes Study 24: a 6-year, randomized, controlled trial comparing sulfonylurea, insulin, and metformin therapy in patients with newly diagnosed type 2 diabetes that could not be controlled with diet therapy. Ann Intern Med. 1998;128:165–175.
Google Scholar
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–853.
Article
Google Scholar
Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA. 1999;281:2005–2012.
PubMed
Article
CAS
Google Scholar
Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2006; 49:1711–1721.
PubMed
Article
CAS
Google Scholar
Barnett AH. New treatments in type 2 diabetes — a focus on the incretin-based therapies. Clin Endocrinol, 2009;70:343–353
Article
Google Scholar
Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368:1696–1705.
PubMed
Article
CAS
Google Scholar
Novartis. Eucreas. Summary of Product Characteristics (UK). Available at: emc.medicines.org.uk/medicine/20735/SPC/Eucreas+50+mg+850+mg+an d+50+mg+1000+mg+film-coated+tablets/. Accessed February 2009.
Halimi S, Schweizer A, Minic B, Foley J, Dejager S. Combination treatment in the management of type 2 diabetes: focus on vildagliptin and metformin as a single tablet. Vasc Health Risk Manag, 2008;4:481–492.
PubMed
CAS
Google Scholar
National Institute for Health and Clinical Excellence (NICE). Type 2 Diabetes: Newer Agents for Blood Glucose Control in Type 2 Diabetes. Full guideline. Draft for consultation. October 2008. Available at: www.nice.org.uk/nicemedia/pdf/T2DDraftGudeline. pdf. Accessed February 2009.
Wulffelé MG, Kooy A, de Zeeuw D, Stehouwer CD, Gansevoort RT. The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type 2 diabetes mellitus: a systematic review. J Intern Med, 2004;256:1–14.
PubMed
Article
Google Scholar
UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352:854–865.
Article
Google Scholar
Novartis. Galvus. Summary of Product Characterisitics (UK). Available at: emc.medicines.org.uk/medicine/20734/SPC/Galvus+50+mg+Tablets/. Accessed February 2009.
Mari A, Sallas WM, He YL, et al. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves modelassessed beta-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab, 2005;90:4888–4894.
PubMed
Article
CAS
Google Scholar
Abbott CA, Yu DM, Woollatt E, et al. Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP) IV homolog, DPP8. Eur J Biochem, 2000;267:6140–6150.
PubMed
Article
CAS
Google Scholar
Olsen C, Wagtmann N. Identification and characterization of human DPP9, a novel homologue of dipeptidyl peptidase IV. Gene, 2002;299:185–193.
PubMed
Article
CAS
Google Scholar
Bailey CJ, Turner RC. Metformin. N Engl J Med, 1996;334:574–579.
PubMed
Article
CAS
Google Scholar
Setter SM, Iltz JL, Thams J, Campbell RK. Metformin hydrochloride in the treatment of type 2 diabetes mellitus: a clinical review with a focus on dual therapy. Clin Ther. 2003; 25: 2991–3026.
PubMed
Article
CAS
Google Scholar
Tahrani AA, Varughese GI, Scarpello JH, Hanna FW. Metformin, heart failure, and lactic acidosis: is metformin absolutely contraindicated? BMJ. 2007; 335: 508–512.
PubMed
Article
CAS
Google Scholar
Bodmer M, Meier C, Krähenbühl S, Jick SS, Meier CR. Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case-control analysis. Diabetes Care. 2008; 31: 2086–2091.
PubMed
Article
CAS
Google Scholar
Mannucci E, Pierazzuoli E, Ognibene A, et al. Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects. Diabetes Care, 2001;24:489–494.
PubMed
Article
CAS
Google Scholar
Lindsay JR, Duffy NA, McKillop AM, et al. Inhibition of dipeptidyl peptidase IV activity by oral metformin in type-2 diabetes. Diabet Med, 2005;22:654–657.
PubMed
Article
CAS
Google Scholar
Hinke SA, Kühn-Wache K, Hoffmann T, Pederson RA, McIntosh CH, Demuth HU. Metformin effects on dipeptidylpeptidase IV degradation of glucagonlike peptide-1. Biochem Biophys Res Commun, 2002;291:1302–1308.
PubMed
Article
CAS
Google Scholar
Dunning BE, Ligueros-Saylan M, D’Alessio DA, et al. Differential effects of DPP-4 inhibition on incretin hormone levels in drug-naive and metformintreated patients with type 2 diabetes. Diabetologia, 2006;49(suppl. 1):110.
Google Scholar
Pospisilik JA, Martin J, Doty T, et al. Dipeptidyl peptidase IV inhibitor treatment stimulates betacell survival and islet neogenesis in streptozotocininduced diabetic rats. Diabetes, 2003;52:741–750.
PubMed
Article
CAS
Google Scholar
Duttaroy A, Voelker F, Merriam K, et al. The DPP-4 inhibitor vildagliptin increases pancreatic beta cell neogenesis and decreases apoptosis. Diabetes, 2005;54(suppl. 1):A141.
Google Scholar
Ahrén B, Foley JE, Pacini G, et al. Improved mealrelated beta-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year. Diabetes Care, 2005;28:1936–1940.
PubMed
Article
Google Scholar
Charbonnel B, Wu M, Karasik A, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care. 29:2638–2643.
Goldstein BJ, Feinglos MN, Lunceford JK, et al. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care, 2007;30:1979–1987.
PubMed
Article
CAS
Google Scholar
Bosi E, Camisasca RP, Collober C, Rochotte E, Garber AJ. Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin. Diabetes Care, 2007;30:890–895.
PubMed
Article
CAS
Google Scholar
Kar P, Holt RI. The effect of sulphonylureas on the microvascular and macrovascular complications of diabetes. Cardiovasc Drugs Ther, 2008;22:207–213.
PubMed
Article
CAS
Google Scholar
Singh SS, Manne N, Pal M. Synthesis of (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile: a key intermediate for dipeptidyl peptidase IV inhibitors. Beilstein J Organic Chem, 2008;4:20.
Google Scholar
Villhauer EB, Brinkman JA, Naderi GB, et al. 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 Chem, 2003;46:2774–2789.
PubMed
Article
CAS
Google Scholar
He YL, Serra D, Wang Y, et al. Pharmacokinetics and pharmacodynamics of vildagliptin in patients with type 2 diabetes mellitus. Clin Pharmacokinet, 2007;46:577–588.
PubMed
Article
CAS
Google Scholar
He YL, Flannery B, Campestrini J, et al. Effect of food on the pharmacokinetics of a vildagliptin/metformin (50/1000 mg) fixed-dose combination tablet in healthy volunteers. Curr Med Res Opin, 2008;24:1703–1709.
PubMed
Article
CAS
Google Scholar
He YL, Sabo R, Campestrini J, et al. The effect of age, gender, and body mass index on the pharmacokinetics and pharmacodynamics of vildagliptin in healthy volunteers. Br J Clin Pharmacol, 2008;65:338–346.
PubMed
Article
CAS
Google Scholar
European Medicines Association. Eucreas, vildagliptin/metformin hydrochloride. Available at: www.emea.europa.eu/humandocs/PDFs/EPAR/eucreas/H-807-en6.pdf. Accessed December 2008.
Ahrén B, Landin-Olsson M, Jansson PA. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels and reduces glucagons levels in type 2 diabetes. J Clin Endocrinol Metab, 2004;89:2078–2084.
PubMed
Article
Google Scholar
Balas B, Baig MR, Watson C, et al. The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients. J Clin Endocrinol Metab, 2007;92:1249–1255.
PubMed
Article
CAS
Google Scholar
He YL, Sadler BM, Sabo R, et al. The absolute oral bioavailability and population-based pharmacokinetic modeling of a novel dipeptidylpeptidase-IV inhibitor, vildagliptin, in healthy volunteers. Clin Pharmacokinet, 2007;46:787–802.
PubMed
Article
CAS
Google Scholar
Pratley RE, Salsali A, Matfin G. Inhibition of dipeptidyl peptidase-4 with vildagliptin: a potential new treatment for type 2 diabetes. Br J Diabetes Vasc Dis, 2006;6:150–156.
Article
CAS
Google Scholar
He YL, Paladini S, Sabia H, et al. Bioequivalence of vildagliptin/metformin fixed-dose combination tablets and a free combination of vildagliptin and metformin in healthy subjects. Int J Clin Pharmacol Ther, 2008;46:259–267.
PubMed
CAS
Google Scholar
Merck Sorono. Glucophage. Summary of Product Characterisitics (UK). Available at: emc.medicines. org.uk/document.aspx?documentId=1043. Accessed February 2009.
Ahrén B, Gomis R, Standl E, et al. Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care, 2004;27:2874–2880.
PubMed
Article
Google Scholar
Bolli G, Dotta F, Rochotte E, Cohen SE. Efficacy and tolerability of vildagliptin vs. pioglitazone when added to metformin: a 24-week, randomized, double-blind study, Diabetes Obes Metab. 2008;10:82–90.
PubMed
CAS
Google Scholar
Ferrannini E, Fonseca V, Zinman B, et al. Fiftytwo-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapy, Diabetes Obes Metab. 2009;11:157–166.
PubMed
Article
CAS
Google Scholar
Braceras R, Blonde L, Banerji M, et al. Vildagliptin is as effective as TZDs in metformin failures: results of GALIANT — a primary care diabetes study. Diabetologia, 2008;51(suppl. 1):S366.
Google Scholar
Brandt I, Joossens J, Chen X, et al. Inhibition of dipeptidyl-peptidase IV catalyzed peptide truncation by Vildagliptin ((2S)-{[(3-hydroxyadamantan-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile). Biochem Pharmacol. 2005;70:134–143.
PubMed
Article
CAS
Google Scholar
Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch C. Emerging role of dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes. Vasc Health Risk Manag, 2008;4:753–768.
PubMed
CAS
Google Scholar
Lambeir AM, Durinx C, Scharpe S, De Meester I. Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci. 2003;40:209–294.
PubMed
Article
CAS
Google Scholar
Dang NH, Morimoto C. CD26: an expanding role in immune regulation and cancer. Histol Histopathol. 2002;17:1213–1226.
PubMed
CAS
Google Scholar
Drucker DJ. Dipeptidyl peptidase-4 inhibition and the treatment of type 2 diabetes: preclinical biology and mechanisms of action. Diabetes Care, 2007;30:1335–1343.
PubMed
Article
CAS
Google Scholar
Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch CL. Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus. Cochrane Database Syst Rev, 2008;(2):CD006739.
PubMed
Google Scholar
Göke B, Hershon K, Kerr D, et al. Efficacy and safety of vildagliptin monotherapy during 2-year treatment of drug-naïve patients with type 2 diabetes: comparison with metformin. Horm Metab Res, 2008;40:892–895.
PubMed
Article
Google Scholar
Novartis. Eucreas, a single-tablet combination of Galvus and metformin, set for launch in first EU countries [press release]. Available at: www.prdomain. com/companies/N/Novartis/newsreleases/200822653863.htm. Accessed December 2008.
Dejager S, Schweizer A, Couturier A, Pratley RE. Achievement of glycaemic targets with vildagliptin. Diabetologia. 2007;50(suppl. 1):S365. Abs. 0885.
Google Scholar
Melikian C, White TJ, Vanderplas A, Dezii CM, Chang E. Adherence to oral antidiabetic therapy in a managed care organization: a comparison of monotherapy, combination therapy, and fixeddose combination therapy. Clin Ther, 2002;24:460–467.
PubMed
Article
Google Scholar