DPP IV inhibitors - Current evidence and future directions

British Journal of Diabetes and Vascular Disease

Volumn 7, Issue 2, 2007, Pages 69-74

  Vilsbøll, Tina ^a   Knop, Filip K ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Dipeptidyl peptidase IV; Glucagon like peptide 1; Glucose dependent insulinotropic polypeptide; Incretin; Type 2 diabetes

Indexed keywords

ALS 2 0426; ANTIDIABETIC AGENT; DIPEPTIDYL PEPTIDASE IV; DIPEPTIDYL PEPTIDASE IV INHIBITOR; GASTRIC INHIBITORY POLYPEPTIDE; GLIPIZIDE; GLITAZONE DERIVATIVE; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 DERIVATIVE; GLUCOSE; HEMOGLOBIN A1C; INCRETIN; INSULIN; INSULIN DERIVATIVE; METFORMIN; PIOGLITAZONE; PLACEBO; PSN 357; PSN 9301; R 1438; R 1499; ROSIGLITAZONE; SAXAGLIPTIN; SITAGLIPTIN; SULFONYLUREA DERIVATIVE; SYR 322; TS 021; UNCLASSIFIED DRUG; VILDAGLIPTIN;

ADD ON THERAPY; BODY WEIGHT; CLINICAL TRIAL; DIABETIC DIET; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG DOSE COMPARISON; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERABILITY; EDEMA; ENZYME INHIBITION; EVIDENCE BASED MEDICINE; GASTROINTESTINAL TOXICITY; GLUCOSE HOMEOSTASIS; GLUCOSE TOLERANCE; GLUCOSE TOLERANCE TEST; GLYCEMIC CONTROL; HEMOGLOBIN BLOOD LEVEL; HUMAN; HYPOGLYCEMIA; INSULIN RESPONSE; METABOLIC REGULATION; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; PANCREAS ISLET CELL FUNCTION; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN SECRETION; REVIEW; SIDE EFFECT; UNSPECIFIED SIDE EFFECT; VOMITING; WEIGHT GAIN;

EID: 34249067690     PISSN: 14746514     EISSN: None     Source Type: Journal    
DOI: 10.1177/14746514070070020401     Document Type: Review

References (65)

1. Smyth S, Heron A. Diabetes and obesity: the twin epidemics. Nat Med 2006;12:75-80.
2. Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia 2003;46:3-19.
3. Muller WA, Faloon GR, Guilar-Parada E, Unger, RH. Abnormal alpha-cell function in diabetes. Response to carbohydrate and protein ingestion. N Engl J Med 1970;283:109-15.
4. Reaven GM, Chen YD, Golay A, Swislocki AL, Jaspan JB. Documentation of hyperglucagonemia throughout the day in nonobese and obese patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1987;64:106-10.
5. Unger RH, Orci L. Glucagon and the A cell: physiology and pathophysiology (second of two parts). N Engl J Med 1981; 304:1575-80.
6. Unger RH, Orci L. Glucagon and the A cell: physiology and pathophysiology (first of two parts). N Engl J Med 1981; 304:1518-24.
7. 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;352:837-53.
8. Vilsboll T. On the role of the incretin hormones GIP and GLP-1 in the pathogenesis of Type 2 diabetes mellitus. Dan Med Bull 2004; 51:364-70.
9. Vilsboll T, Holst JJ. Incretins, insulin secretion and Type 2 diabetes mellitus. Diabetologia 2004;47:357-66.
10. Nauck MA, Kleine N, Orskov C, Holst JJ, Willms B, Creutzfeldt W. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993;36:741-4.
11. Zander M, Madsbad S, Madsen JL, Holst JJ. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 2002;359:824-30.
12. Deacon CF, Nauck MA, Toft-Nielsen M, Pridal L, Willms B, Holst JJ. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes 1995;44:1126-31.
13. Deacon CF, Johnsen AH, Holst JJ. 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 Metab 1995;80:952-7.
14. Kieffer TJ, McIntosh CH, Pederson RA. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology 1995;136:3585-96.
15. 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.
16. Orskov C, Wettergren A, Holst JJ. Secretion of the incretin hormones glucagon-like peptide-1 and gastric inhibitory polypeptide correlates with insulin secretion in normal man throughout the day. Scand J Gastroenterol 1996;31:665-70.
17. Layer P, Holst JJ, Grandt D, Goebell H. Ileal release of glucagon-like peptide-1 (GLP-1). Association with inhibition of gastric acid secretion in humans. Dig Dis Sci 1995;40:1074-82.
18. Ding WG, Renstrom E, Rorsman P, Buschard K, Gromada J. Glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide stimulate Ca2+-induced secretion in rat alpha-cells by a protein kinase A-mediated mechanism. Diabetes 1997;46:792-800.
19. Gromada J, Holst JJ, Rorsman P. Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1. Pflugers Arch 1998;435:583-94.
20. Estall JL, Drucker DJ. Glucagon and glucagon-like peptide receptors as drug targets. Curr Pharm Des 2006;12:1731-50.
21. Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 1993;91:301-07.
22. Orskov C, Holst JJ, Nielsen OV. Effect of truncated glucagon-like peptide-1 [proglucagon-(78-107) amide] on endocrine secretion from pig pancreas, antrum, and nonantral stomach. Endocrinology 1988; 123:2009-13.
23. Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest 1998;101:515-20.
24. Willms B, Werne J, Holst JJ, Orskov C, Creutzfeldt W, Nauck MA. Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(736) amide in type 2 (noninsulin-dependent) diabetic patients. J Clin Endocrinol Metab 1996;81:327-32.
25. Nauck MA, Niedereichholz U, Ettler R et al. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol 1997;273:E981-E988.
26. Nikolaidis LA, Mankad S, Soko GG et al. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation 2004;109:962-96.
27. Egan JM, Bulotto A, Hui H, Perfetti R. GLP-1 receptor agonists are growth and differentiation factors for pancreatic islet beta cells. Diabetes Metab Res Rev 2003;19:115-23.
28. Xu G, Kaneto H, Lopez-Avalos MD, Weir GC, Bonner-Weir S. GLP-1/exendin-4 facilitates beta-cell neogenesis in rat and human pancreatic ducts. Diabetes Res Clin Pract 2006;73:107-10.
29. Stoffers DA, Kieffer TJ, Hussai MA et al. Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas. Diabetes 2000;49:741-8.
30. Zhou J, Wang X, Pineyro MA, Egan JM. Glucagon-like peptide 1 and exendin-4 convert pancreatic AR42J cells into glucagon- and insulin-producing cells. Diabetes 1999;48:2358-66.
31. Hui H, Nourparvar A, Zhao X, Perfetti R. Glucagon-like peptide-1 inhibits apoptosis of insulin-secreting cells via a cyclic 5′-adenosine monophosphate-dependent protein kinase A- and a phosphatidylinositol 3-kinase-dependent pathway. Endocrinology 2003;144:1444-55.
32. Brubaker PL, Drucker DJ. Minireview. Glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system. Endocrinology 2004;145:2653-9.
33. Mentlein R, Gallwit B, Schmidt WE. Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem 1993;214:829-35.
34. Lambeir AM, Durinx C, Scharpe S, De MI. 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;40:209-94.
35. Ryskjaer J, Deacon CF, Carr RD et al. Plasma dipeptidyl peptidase-IV activity in patients with type-2 diabetes mellitus correlates positively with HbAlc levels, but is not acutely affected by food intake. Eur J Endocrinol 2006;155:485-93.
36. Marguet D, Baggio L, Kobayashi T et al. Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proc Natl Acad Sci USA 2000;97:6874-9.
37. Deacon CF, Hughes TE, Holst JJ. Dipeptidyl peptidase IV inhibition potentiates the insulinotropic effect of glucagon-like peptide 1 in the anesthetized pig. Diabetes 1998;47:764-9.
38. Deacon CF, Danielsen P, Klarskov L, Olesen M, Holst, J. Dipeptidyl peptidase IV inhibition reduces the degradation and clearance of GIP and potentiates its insulinotropic and antihyperglycemic effects in anesthetized pigs. Diabetes 2001;50:1588-97.
39. Vilsboll T, Krarup T, Madsbad S, Holst JJ. Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects. Regul Pept 2003;114:115-21.
40. Nauck M, Stockmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 1986; 29:46-52.
41. Kjems LL, Holst JJ, Volun A, Madsbad S. The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes 2003;52:380-6.
42. Højberg P, Zander M, Vilsboll T et al. Effect of 4 weeks of near-normalization of blood glucose on beta-cell sensitivity to glucose and GLP-1 in type 2 diabetic patients (Abstract). Diabetes 2005;A362.
43. Knop FK, Vilsboll T, Hojberg P et al. The incretin effect is preserved in glucose tolerant patients with chronic pancreatitis - but reduced in patients with chronic pancreatitis and secondary diabetes mellitus (Abstract). Diabetes 2006;1484.
44. Deacon CF, Holst JJ. Dipeptidyl peptidase IV inhibitors: a promising new therapeutic approach for the management of type 2 diabetes. Int J Biochem Cell Biol 2006;38:831-44.
45. Deacon CF, Wamberg S, Bie P, Hughes TE, Holst J. Preservation of active incretin hormones by inhibition of dipeptidyl peptidase IV suppresses meal-induced incretin secretion in dogs. J Endocrinol 2002; 172:355-62.
46. Mu J, Woods J, Zhou YP et al. chronic inhibition of dipeptidyl peptidase-4 with a sitagliptin analog preserves pancreatic {beta}-cell mass and function in a rodent model of type 2 diabetes. Diabetes 2006;55:1695-704.
47. Ahren B, Landin-Olsson M, Jansson PA, Svensson M, Holmes D, Schweizer A. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab 2004;89:2078-84.
48. Pratley RE, Jauffret-Kamel 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.
49. Rosenstock J, Baron M, Schweizer A, Mills D, Dejager S. Vildagliptin is as effective as rosiglitazone in lowering HBa1c but without weight gain in drug naive patients with type 2 diabetes (T2DM) (Abstract). Diabetes 2006;A133.
50. Raz I, Hanefeld M, Xu L, Caria C, Williams-Herman D, Khatami H. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia 2006;49: 2564-71. Epub 2006 Sep 26.
51. Aschner P, Kipnes M, Lunceford J et al. Sitagliptin monotherapy improved glycaemic control in patients with type 2 diabetes (Abstract). Diabetologia 2006:5.
52. Foneca V, Dejager S, Albrecht D, Shirt L, Schweizer A: Vildagliptin as Add-On to Insulin in Patients with Type 2 Diabetes (T2DM) (Abstract). Diabetes 2006;467.
53. Meininger G, Charbonnel B, Karasik A, Liu J, Wu MMA. Efficacy and safety of sitagliptin added to ongoing metformin therapy in type 2 diabetes patients who were inadequately controlled on metformin alone (Abstract). Diabetologia 2006;0006.
54. Rosenstock J, Brazg R, Andryuk P, McCrary Sisk C, Lu K, Stein P. Addition of Sitagliptin to pioglitazone improved glycaemic control with neutral weight effect over 24-weeks in inadequately controlled type 2 diabetes (Abstract). Diabetologia 2006;39.
55. Ahren B, Pacini G, Foley JE, Schweizer A. Improved meal-related 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;28:1936-40.
56. Mari A, Sallas WM, He YL et al. Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab 2005; 90:4888-94.
57. Xu L, Dalla Man C, Cobelli C et al. Regulation of beta cell function by incretin hormones (Abstract). Diabetologia 2006;0653.
58. Ahren B, Gomis R, Standl E, Mills D, Schweizer A. Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care 2004;27:2874-80.
59. Riddle MC, Henry RR, Poon TH et al. Exenatide elicits sustained glycaemic control and progressive reduction of body weight in patients with type 2 diabetes inadequately controlled by sulphonylureas with or without metformin. Diabetes Metab Res Rev 2006;22:483-91.
60. Vilsboll T, Zdravkovic M, Le-Thi T et al. Liraglutide significantly improves glycemic control, and lowers body weight without risk of either major or minor hypoglycemic episodes in subjects with type 2 diabetes (Abstract). Diabetes Suppl 2006;A115.
61. Boden G, Zhan M: Recent findings concerning thiazolidinediones in the treatment of diabetes. Expert Opin Investig Drugs 2006; 15:243-50.
62. Pederson RA, Kieffer TJ, Pauly R, Kofod H, Kwong J, McIntosh CH. The enteroinsular axis in dipeptidyl peptidase IV-negative rats. Metabolism 1996;45:1335-41.
63. Lankas GR, Leiting B, Roy RS et al. Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9. Diabetes 2005; 54:2988-94.
64. Vilsboll T, Krarup T, Madsbad S, Holst JJ. Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients. Diabetologia 2002;45:1111-19.
65. Vilsboll T, Knop FK, Krarup T et al. The pathophysiology of diabetes involves a defective amplification of the late-phase insulin response to glucose by glucose-dependent insulinotropic polypeptide-regardless of etiology and phenotype. J Clin Endocrinol Metab 2003;88:4897-903.