Incretin mimetics and dipeptidyl peptidase 4 inhibitors in clinical trials for the treatment of type 2 diabetes

Expert Opinion on Investigational Drugs

Volumn 17, Issue 6, 2008, Pages 845-853

  Mikhail, Nasser ^a  

^a UCLA MEDICAL CENTER   (United States)

Author keywords

Dipeptidyl peptidase inhibitors; Exenatide; Incretins; Sitagliptin; Type 2 diabetes; Vildaglipcin

Indexed keywords

ACARBOSE; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EXENDIN 4; GLIBENCLAMIDE; GLIMEPIRIDE; GLIPIZIDE; GLITAZONE DERIVATIVE; GLUCAGON LIKE PEPTIDE 1; HEMOGLOBIN A1C; INCRETIN; INSULIN; INSULIN ASPART; INSULIN GLARGINE; LIRAGLUTIDE; METFORMIN; ORAL ANTIDIABETIC AGENT; PIOGLITAZONE; PLACEBO; ROSIGLITAZONE; SITAGLIPTIN; SULFONYLUREA; SULFONYLUREA DERIVATIVE; VILDAGLIPTIN;

ADD ON THERAPY; ADJUVANT THERAPY; ANAPHYLAXIS; ANGIONEUROTIC EDEMA; BACKACHE; BODY WEIGHT; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CONSTIPATION; DIARRHEA; DIZZINESS; DOSAGE SCHEDULE COMPARISON; DRUG ACTIVITY; DRUG COST; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG FORMULATION; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG MEGADOSE; DRUG POTENTIATION; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; GASTROINTESTINAL SYMPTOM; GLUCOSE BLOOD LEVEL; GLYCEMIC CONTROL; HEADACHE; HUMAN; HYPOGLYCEMIA; MONOTHERAPY; MOTOR DYSFUNCTION; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; PANCREATITIS; RECOMMENDED DRUG DOSE; REVIEW; RHINOPHARYNGITIS; SIDE EFFECT; SINGLE DRUG DOSE; STEVENS JOHNSON SYNDROME; SWEATING; UNSPECIFIED SIDE EFFECT; URINARY TRACT INFECTION; VOMITING; WEIGHT GAIN; WEIGHT REDUCTION;

ADAMANTANE; ANTIGENS, CD26; BODY WEIGHT; CLINICAL TRIALS, PHASE III AS TOPIC; DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; GLUCAGON-LIKE PEPTIDE 1; HEMOGLOBIN A, GLYCOSYLATED; HUMANS; HYPOGLYCEMIA; HYPOGLYCEMIC AGENTS; INCRETINS; INSULIN; NAUSEA; NITRILES; PEPTIDES; PYRAZINES; PYRROLIDINES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RECEPTORS, GLUCAGON; TRIAZOLES; VENOMS; VOMITING;

EID: 45749095401     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.17.6.845     Document Type: Review

References (61)

1. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006;368:1696-705
2. Ebert R, Unger H, Creutzfeldt W. Preservation of incretin activity after removal of gastric inhibitory polypeptide (GIP) from gut extracts by immunoadsorption. Diabetologia 1983;24:449-54
3. Schirra J, Nicolaus M, Roggel R, et al. Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans. Gut 2006;55:243-51
4. Kreymann, Ghatei MA, Williams G, Bloom SR. Glucagon-like peptide-17-36: a physiological incretin in man. Lancet 1987;2:1300-4.
5. Elahi D, McAloon-Dyke M, Fukagawa NK, et al. The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-37) in normal and diabetic subjects. Regul Pept 1994;51:63-74
6. Schirra J, Sturm K, Leicht P et al. Exendin (9-39) amide is an antagonist of glucagon-like peptide- 1 (7-36) amide in humans. J Clin Invest 1998;101:1421-30
7. Nauck MA, Heimesaat MM, Orskov C, et al. Preserved incretin activity of GAP-1 (7-36 amide) but not of synthetic human GIP in patients with type 2 diabetes mellitus. J Clin Invest 1993;91:301-7
8. Meier JJ, Goetze O, Anstipp J, et al. Gastric inhibitory polypeptide (GIP) does not inhibit gastric emptying in man. Am J Physiol 2003;286:E621-5
9. Habener JF. The incretin notion and its relevance to diabetes. Endocrinol Metab Clin North Am 1993;22:775-95
10. Gutniak M, Orskov C, Holst JJ, et al. Antidiabetogenic effect of glucagon-like peptide-1 (7-36) amide in normal subjects and patients with diabetes mellitus. N Engl J Med 1992;326:1316-22
11. Nathan DM, Schreiber E, Fogel H, et al. Insulinotropic action of glucagon-like peptide-l-(7-37) in diabetic and nondiabetic subjects. Diabetes Care 1992;15:270-6
12. Krarup T, Saubrey N, Moody AJ, et al. Effect of porcine gastric inhibitory polypeptide on β-cell function in type I and type II diabetes mellitus. Metabolism 1987;36:677-82
13. Vilsboll T, Krarup T, Deacon C, et al. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetes. Diabetes 2001;50:609-13
14. Toft-Nielsen M, Damholt MB, Madsbad S, et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001;86:3717-23
15. Lugari R, Dei Cas A, Ugolotti D, et al. Evidence for early impairment of glucagon-like peptide 1-induced insulin secretion in human type 2 (non-insulin dependent) diabetes. Horm Metab Res 2002;34:150-4
16. Vilsboll T, Agerso H, Krarup T, Holst JJ. Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. J Clin Endocrinol Metab 2003;88:220-4
17. DeFronzo RA, Ratner RE, Han J, et al. Effects of exenatide (Exendin-4) on glycemic control over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 2005;28:1092-100
18. Buse JB, Henry RR, Han J, et al. Effects of exenatide (Exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004;27:2628-35
19. Kendall DM, Riddle MC, Rosenstock J, et al. Effects of exenatide (Exendin-4) on glycernic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 2005;28:1083-91
20. Zinman B, Hoogwerf BJ, Garcia SD, et al. The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes. Ann Intern Med 2007;146:477-85
21. Kim D, MacConell L, Zhuang D, et al. Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. Diabetes Care 2007;30:1487-93
22. American Diabetes Association. Standards of medical care in diabetes, 2007. Diabetes Care 2007;30(Suppl 1):S4-41
23. Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes. Systemic review and meta-analysis. JAMA 2007;298:194-206.
24. Heine RJ, Van Gaal LF, Johns D, et al.; GWAA Study Group. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes. A randomized trial. Ann Intern Med 2005;143:559-69
25. Nauck MA, Duran S, Kim D, et al. A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority trial. Diabetologia 2007;50:259-67
26. Davis SN, Johns D, Maggs D, et al. Exploring the substitution of exenatide for insulin in patients with type 2 diabetes treated with insulin in combination with oral antidiabetes agents. Diabetes Care 2007;30:2767-72
27. Blonde L, Klein EJ, Han J, et al. Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab 2006;8:436-47.
28. Degn KB, Brock B, Juhl CB, et al. Effect of intravenous infusion of exenatide (synthetic exendin-4) on glucose-dependent insulin secretion and counterregulation during hypoglycemia. Diabetes 2004;53:2397-403
29. Gutniak MK, Junitti-Berggren L, Hellstrom P, et al. Glucagon-like peptide 1 enhances the insulinotropic effect of glibenclamide in NIDDM patients and in the perfused rat pancreas. Diabetes Care 1996;19:857-63
30. Ahmad SR, Swann J. Exenatide and rare 4 adverse events [letter]. N Engl J Med 2008;358:1970-2
31. Harder H, Mscodont LN, Thi TDT, Drmedski AA. The effect of liraglutide, a long-acting glucagon-like peptide 1 derivative, on glycemic control, body composition, and 24-h energy expenditure in patients with type 2 diabetes. Diabetes Care 2004;27:1915-21.
32. Madsbad S, Schmitz O, Rankam J, et al. Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211). Diabetes Care 2004;27:1335-42
33. Aschner P, Kipnes MS, Lunceford JK, et al. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 2006;29:2632-7
34. Raz I, Hanefeld M, Xu L, et al. for the Sitagliptin Study 023 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia 2006;49:2564-71
35. Pratley RE, Kamel-Jauffret S, Galbreath E, Holmes D. Twelve-week monotherapy with the DPP-4 inhibitor vildagliptin improves glycemic control in subjects with type 2 diabetes. Horm Metab Res 2006;38:423-8
36. Pi-Sunyer FX, Schweizer A, Mills D, Dejager S. Efficacy and tolerability of vildagliptin monotherapy in drug-naive patients with type 2 diabetes. Diabetes Res Clin Pract 2007;76:132-8
37. Charbonnel B, Karasik A. Liu J, et al.; Sitagliptin Study 020 Group. 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 2006;29:2638-43
38. Bosi E, Camisasca RP, Collober C, et al. Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin. Diabetes Care 2007;30:890-5
39. Goldstein BJ, Feinglos MN, Lunceford JK, et al.; Sitagliptin 036 Study Group. 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;30:1979-87
40. Mannuci E, Ognibene A, Cremasco F, et al. Effect of metformin on glucagon-like peptide (GLP-1) and leptin levels in obese nondiabetic subjects. Diabetes Care 2001;24:489-94
41. Green BD, Irwin N, Duffy NA, et al. Inhibition of dipeptidyl peptidase-IV activity, by meformin enhances the antidiabetic effects of glucagon-like peptide 1. Eur J Pharmacol 2006;547:192-9
42. Hermansen K, Kipnes M, Luo E, et al.; Sitagliptin Study 035 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes inadequately controlled on glimepiride and metformin. Diabetes Obes Metab 2007;9:733-45
43. Garber AJ, Foley JE, Banerji MA, et al. Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea. Diabetes Obes Metab 2008; Feb 18 [Epub ahead of print]
44. Rosenstock J, Brazg R, Andryuk PJ, et al.; Sitagliptin Study 019 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing ploglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther 2006;28:1556-68
45. Garber AJ, Schweizer A, Baron A, et al. Vildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetes failing thiazolidinedionw monotherapy: a randomized, placebo-controlled study. Diabetes Obes Metab 2007;9:166-74
46. Rosenstock J, Baron MA, Camisasca RP, et al. Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes. Diabetes Obes Metab 2007;9:175-85
47. Fonesca V, Dejager S, Albrecht D, et al. Addition of vildagliptin to insulin improves glycaemic control in type 2 diabetes. Diabetologia. 2007;50:1148-55
48. Schweizer A, Couturier A, Foley JE, Dejager S. Comparison between vildagliptin and metformin to sustain reductions in HbA(1c) over 1 year in drug-naïve patients with type 2 diabetes. Diabet Med 2007; 24:955-61
49. Nauck MA, Meininger G, Sheng D, et al.; Sitagliptin Study 024 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab 2007;9:194-205
50. Rosenstock J, Baron MA, Dejager S, et al. Comparison of vildagliptin and rosiglitazone monotherapy in patients with type 2 diabetes. Diabetes Care 2007;30:217-23
51. Bolli G, Dotta F, Rochette 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
52. Pan C, Yang W, Barona JP, et al. Comparison of vildagliptin and acarbose monotherapy in patients with type 2 diabetes: a 24-week, double-blind, randomized trial. Diabet Med 2008;25:435-41
53. Januvia (sitagliptin phosphate). Product insert. Merk & Co., Station, NJ, USA; 2007
54. Xu G, Stoffers DA, Habener JF, Bonner-Weir S. Exendin-4 stimulates both β-cell replication and neogenesis, resulting in increased β-cell mass and improved tolerance in diabetic rats. Diabetes 1999; 48:2270-6
55. Mu J, Woods J, Zhou Y, et al. Chronic inhibition of dipeptidyl peptidase-4 with a sitagliptin-analog preserves pancreatic β-cell mass and function in a rodent model of type 2 diabetes. Diabetes 2006;55:1695-704
56. Barnett A. DPP-4 inhibitors and their potential role in the management of type 2 diabetes. Int J Clin Pract 2006;60:1454-70
57. Nathan DM, Buse JB, Davidson M, et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 2006;29:1963-72
58. Bolen S, FeldmanL, Vassy J, et al. Systemic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med 2007;147:386-99
59. Mikhail N, Exenatide: a novel approach for treatment of type 2 diabetes. South Med J 2006;99:1271-9
60. Linnebjerg H, Kothare PA, Park S, et al. Effect of renal impairment on the pharmacokinetics of exenatide. Br J Clin Pharmacol 2007;64:317-27
61. Bergman AJ, Cote J, Yi B, et al. Effect of renal insufficiency on the pharmacokinetics of sitagliptin, a dipeptidyl peptidase-4 inhibitor. Diabetes Care 2007;30:1862-4