Incretin-based therapy: A powerful and promising weapon in the treatment of type 2 diabetes mellitus

Diabetes Therapy

Volumn 2, Issue 2, 2011, Pages 101-121

  Koliaki, Chrysi ^a   Doupis, John ^b  

^a NATIONAL AND KAPODISTRIAN UNIVERSITY OF ATHENS   (Greece)

^b Salamis Naval Base Hospital   (Greece)

Author keywords

GLP 1 analogs; GLP 1 receptor agonists; glucagon like peptide 1; glucagonlike peptide 1 receptor; incretins; pleiotropic effects; type 2 diabetes mellitus

Indexed keywords

ALBIGLUTIDE; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EXENDIN 4; GLIMEPIRIDE; GLITAZONE DERIVATIVE; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; HORMONE RECEPTOR STIMULATING AGENT; INCRETIN; INSULIN GLARGINE; LIRAGLUTIDE; LONG ACTING DRUG; METFORMIN; PLACEBO; ROSIGLITAZONE; SAXAGLIPTIN; SITAGLIPTIN; SULFONYLUREA; TASPOGLUTIDE; UNCLASSIFIED DRUG; VILDAGLIPTIN;

ADJUVANT THERAPY; APOPTOSIS; CELL PROLIFERATION; CONTINUOUS INFUSION; COST EFFECTIVENESS ANALYSIS; DOSAGE SCHEDULE COMPARISON; DOSE RESPONSE; DRUG COST; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG SAFETY; FLATULENCE; GASTROINTESTINAL SYMPTOM; GLUCAGON RELEASE; GLYCEMIC CONTROL; HEART PROTECTION; HORMONAL THERAPY; HUMAN; HYPERGLUCAGONEMIA; HYPERGLYCEMIA; INSULIN RELEASE; INSULIN RESISTANCE; INTRAABDOMINAL FAT; LIFESTYLE MODIFICATION; NAUSEA; NEUROPROTECTION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PANCREAS ISLET DISEASE; PANCREATITIS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; RENAL PROTECTION; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; SUSTAINED RELEASE FORMULATION; SYSTOLIC BLOOD PRESSURE; VOMITING; WEIGHT REDUCTION;

EID: 79955930032     PISSN: 18696953     EISSN: 18696961     Source Type: Journal    
DOI: 10.1007/s13300-011-0002-3     Document Type: Review

References (86)

1. International Diabetes Federation. United Nations Resolution 61/225: World Diabetes Day. 2008. Available at: www. idf. org/webdata/docs/World_Diabetes_Day_Media_Kit. pdf. Accessed: January 28, 2011.
2. International Diabetes Federation. Diabetes Atlas. Executive Summary, second edition. Brussels: International Diabetes Federation; 2003.
3. Wajchenberg BL. Beta-cell failure in diabetes and preservation by clinical treatment. Endocr Rev. 2007; 28: 187-218.
4. Munshi M. Managing the "geriatric syndrome" in patients with type 2 diabetes. Consult Pharm. 2008; 23(suppl. B): 12-16.
5. Fox K M, Gerber 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.
6. Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia 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. Diabetes Care. 2006; 29: 1963-1972.
7. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA. 2002; 287: 360-372.
8. 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: 665-670.
9. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007; 132: 2131-2157.
10. Kieffer TJ, Habener JF. The glucagon-like peptides. Endocr Rev. 1999; 20: 876-913.
11. Vilsbøll 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: 4897-4903.
12. Runge S, Thøgersen H, Madsen K, Lau J, Rudolph R. Crystal structure of the ligand-bound glucagonlike peptide-1 receptor extracellular domain. J Biol Chem. 2008; 283: 11340-11347.
13. Nauck MA, Kleine N, Orskov C, et al. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia. 1993; 36: 741-744.
14. Drucker DJ, Philippe J, Mojsov S, Chick WL, Habener JF. Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci USA. 1987; 84: 3434-3438.
15. Buteau J, Foisy S, Joly E, Prentki M. Glucagon-like peptide 1 induces pancreatic beta-cell proliferation via transactivation of the epidermal growth factor receptor. Diabetes. 2003; 52: 124-132.
16. 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.
17. Toft-Nielsen MB, 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: 3717-3723.
18. Nauck M, Stöckmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986; 29: 46-52.
19. Vilsbøll 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: 1111-1119.
20. Spiller RC, Trotman IF, Higgins BE, et al. The ileal brake-inhibition of jejunal motility after ileal fat perfusion in man. Gut. 1984; 25: 365-374.
21. Meier J J, Gethmann A, Götze O et al. Glucagonlike peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans. Diabetologia. 2006; 49: 452-458.
22. Nagell CF, Wettergren A, Ørskov C, Holst JJ. Inhibitory effect of GLP-1 on gastric motility persists after vagal deafferentation in pigs. Scand J Gastroenterol. 2006; 41: 667-672.
23. Wettergren A, Wojdemann M, Meisner S, et al. The inhibitory effect of glucagon-like peptide-1 (GLP-1) 7-36 amide on gastric acid secretion in humans depends on an intact vagal innervation. Gut. 1997; 40: 597-601.
24. 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: 824-830.
25. Williams DL. Minireview: finding the sweet spot: peripheral versus central glucagon-like peptide 1 action in feeding and glucose homeostasis. Endocrinology. 2009; 150: 2997-3001.
26. During MJ, Cao L, Zuzga DS, et al. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med. 2003; 9: 1173-1179.
27. Grieve DJ, Cassidy RS, Green BD. Emerging cardiovascular actions of the incretin hormone glucagon-like peptide-1: potential therapeutic benefits beyond glycaemic control? Br J Pharmacol. 2009; 157: 1340-1351.
28. Ban K, Noyan-Ashraf MH, Hoefer J, et al. Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and independent pathways. Circulation. 2008; 117: 2340-2350.
29. Nikolaidis LA, Elahi D, Hentosz T, et al. Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy. Circulation. 2004; 110: 955-961.
30. Timmers L, Henriques JP, de Kleijn DP, et al. Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol. 2009; 53: 501-510.
31. Poornima I, Brown SB, Bhashyam S, et al. Chronic glucagon-like peptide-1 infusion sustains left ventricular systolic function and prolongs survival in the spontaneously hypertensive heart failureprone rat. Circ Heart Fail. 2008; 1: 153-160.
32. Noyan-Ashraf MH, Momen MA, Ban K, et al. GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice. Diabetes. 2009; 58: 975-983.
33. Nikolaidis LA, Mankad S, Sokos 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: 962-965.
34. Sokos GG, Nikolaidis LA, Mankad S, et al. Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail. 2006; 12: 694-699.
35. Sokos GG, Bolukoglu H, German J, et al. Effect of glucagon-like peptide-1 (GLP-1) on glycemic control and left ventricular function in patients undergoing coronary artery bypass grafting. Am J Cardiol. 2007; 100: 824-829.
36. Klonoff DC, Buse JB, Nielsen LL, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin. 2008; 24: 275-286.
37. Mussig K, Oncu A, Lindauer P, et al. Effects of intravenous glucagon-like peptide-1 on glucose control and hemodynamics after coronary artery bypass surgery in patients with type 2 diabetes. Am J Cardiol. 2008; 102: 646-647.
38. Basu A, Charkoudian N, Schrage W, et al. Beneficial effects of GLP-1 on endothelial function in humans: dampening by glyburide but not by glimepiride. Am J Physiol. 2007; 293: E1289-1295.
39. Carraro-Lacroix LR, Malnic G, Girardi ACC. Regulation of Na+/H+ exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells. Am J Physiol 2009; 29: F1647-1655.
40. Gutzwiller JP, Tschopp S, Bock A, et al. Glucagon-like peptide 1 induces natriuresis in healthy subjects and in insulin-resistant obese men. J Clin Endocrinol Metab. 2004; 89: 3055-3061.
41. Benito E, Blazquez E, Bosch MA. Glucagon-like peptide-1-(7-36)amide increases pulmonary surfactant secretion through a cyclic adenosine 3, 5-monophosphate-dependent protein kinase mechanism in rat type II pneumocytes. Endocrinology. 1998; 139: 2363-2368.
42. Vilsbøll T. Liraglutide: a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus. Expert Opin Investig Drugs. 2007; 16: 231-237.
43. Eng J, Kleinman WA, Singh L, et al. Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem. 1992; 267: 7402-7405.
44. Thorens B, Porret A, Bühler L, et al. Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor. Diabetes. 1993; 42: 1678-1682.
45. European Medicines Agency: EPARs for authorised medicinal products for human use. Byetta: Scientific Discussion (6). Available at: www. ema. europa. eu/humandocs/Humans/EPAR/byetta/byetta. htm. Accessed: January 28, 2011.
46. Kolterman OG, Kim DD, Shen L, et al. Pharmacokinetics, pharmacodynamics and safety of exenatide in patients with type 2 diabetes mellitus. Am J Health Syst Pharm. 2005; 62: 173-181.
47. Iltz JL, Baker DE, Setter SM, Keith Campbell R. Exenatide: an incretin mimetic for the treatment of type 2 diabetes mellitus. Clin Ther. 2006; 28: 652-665.
48. DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005; 28: 1092-1100.
49. Buse JB, Sesti G, Schmidt WE, et al. Switching to once-daily liraglutide from twice-daily exenatide further improves glycemic control in patients with type 2 diabetes using oral agents. Diabetes Care. 2010; 33: 1300-1303.
50. Tzefos M, Olin JL. Glucagon-like peptide-1 analog and insulin combination therapy in the management of adults with type 2 diabetes mellitus. Ann Pharmacother. 2010; 44: 1294-1300.
51. Barnett AH, Burger J, Johns D, et al. Tolerability and efficacy of exenatide and titrated insulin glargine in adult patients with type 2 diabetes previously uncontrolled with metformin or a sulfonylurea: a multinational, randomized, openlabel, two-period, crossover noninferiority trial. Clin Ther. 2007; 29: 2333-2348.
52. Moretto TJ, Milton DR, Ridge TD, et al. Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2008; 30: 1448-1460.
53. Knudsen LB, Nielsen PF, Huusfeldt PO, et al. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. J Med Chem. 2000; 43: 1664-1669.
54. Sturis J, Gotfredsen CF, Rømer J, et al. GLP-1 derivative liraglutide in rats with beta-cell deficiencies: influence of metabolic state on betacell mass dynamics. Br J Pharmacol. 2003; 140: 123-132.
55. Toso C, McCall M, Emamaullee J, et al. Liraglutide, a long-acting human glucagon-like peptide 1 analogue, improves human islet survival in culture. Transpl Int. 2010; 23: 259-265.
56. Raun K, von Voss P, Gotfredsen CF, Golozoubova V, Rolin B, Knudsen LB. Liraglutide, a long-acting glucagon-like peptide-1 analog, reduces body weight and food intake in obese candy-fed rats, whereas a dipeptidyl peptidase-IV inhibitor, vildagliptin, does not. Diabetes. 2007; 56: 8-15.
57. Degn KB, Juhl CB, Sturis J, et al. One week's treatment with the long-acting glucagonlike peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and alpha- and beta-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes. 2004; 53: 1187-1194.
58. Horowitz M, Flint A, Doran S, et al. The once-daily human GLP-1 analogue liraglutide decreases postprandial hunger and energy intake [Abstract 555-P]. Diabetes. 2008; 57(suppl. 1): A165.
59. Buse JB, Rosenstock J, Sesti G, et al; LEAD-6 Study Group. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, openlabel trial (LEAD-6). Lancet. 2009; 374: 39-47.
60. Garber A, Henry R, Ratner R, et al; LEAD-3 (Mono) Study Group. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009; 373: 473-481.
61. Marre M, Shaw J, Brändle M, et al; LEAD-1 SU study group. Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU). Diabet Med. 2009; 26: 268-278.
62. Russell-Jones D, Vaag A, Schmitz O, et al; Liraglutide Effect and Action in Diabetes 5 (LEAD-5) met+SU Study Group. Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial. Diabetologia. 2009; 52: 2046-2055.
63. Zinman B, Gerich J, Buse JB, et al; LEAD-4 Study Investigators. Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD). Diabetes Care. 2009; 32: 1224-1230.
64. Pratley RE, Nauck M, Bailey T, et al; 1860-LIRADPP-4 Study Group. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet. 2010; 375: 1447-1456.
65. Pratley RE, Nauck M, Frid A, Hermansen K, et al; LEAD-2 Study Group. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009; 32: 84-90.
66. Fonseca VA, Zinman B, Nauck MA, Goldfine AB, Plutzky J. Confronting the type 2 diabetes epidemic: the emerging role of incretin-based therapies. Am J Med. 2010; 123: S2-S10.
67. Bode BW, Testa MA, Magwire M, et al; LEAD-3 Study Group. Patient-reported outcomes following treatment with the human GLP-1 analogue liraglutide or glimepiride in monotherapy: results from a randomized controlled trial in patients with type 2 diabetes. Diabetes Obes Metab. 2010; 12: 604-612.
68. Montanya E, Sesti G. A review of efficacy and safety data regarding the use of liraglutide, a oncedaily human glucagon-like peptide 1 analogue, in the treatment of type 2 diabetes mellitus. Clin Ther. 2009; 31: 2472-2488.
69. Bush MA, Matthews JE, De Boever EH, et al. Safety, tolerability, pharmacodynamics and pharmacokinetics of albiglutide, a long-acting glucagon-like peptide-1 mimetic, in healthy subjects. Diabetes Obes Metab. 2009; 11: 498-505.
70. Tomkin GH. Albiglutide, an albumin-based fusion of glucagon-like peptide 1 for the potential treatment of type 2 diabetes. Curr Opin Mol Ther. 2009; 11: 579-588.
71. Rosenstock J, Reusch J, Bush M, Yang F, Stewart M; Albiglutide Study Group. Potential of albiglutide, a long-acting GLP-1 receptor agonist, in type 2 diabetes: a randomized controlled trial exploring weekly, biweekly, and monthly dosing. Diabetes Care. 2009; 32: 1880-1886.
72. Baggio LL, Huang Q, Brown TJ, Drucker DJ. A recombinant human glucagon-like peptide (GLP)-1-albumin protein (albugon) mimics peptidergic activation of GLP-1 receptor-dependent pathways coupled with satiety, gastrointestinal motility, and glucose homeostasis. Diabetes. 2004; 53: 2492-2500.
73. Retterstøl K. Taspoglutide: a long acting human glucagon-like polypeptide-1 analogue. Expert Opin Investig Drugs. 2009; 18: 1405-1411.
74. Kapitza C, Heise T, Birman P, et al. Pharmacokinetic and pharmacodynamic properties of taspoglutide, a once-weekly, human GLP-1 analogue, after single-dose administration in patients with type 2 diabetes. Diabet Med. 2009; 26: 1156-1164.
75. Nauck MA, Ratner RE, Kapitza C, Berria R, Boldrin M, Balena R. Treatment with the human once-weekly glucagon-like peptide-1 analog taspoglutide in combination with metformin improves glycemic control and lowers body weight in patients with type 2 diabetes inadequately controlled with metformin alone: a double-blind placebo-controlled study. Diabetes Care. 2009; 32: 1237-1243.
76. Tracy MA, Ward KL, Firouzabadian L, et al. Factors affecting the degradation rate of poly(lactideco-glycolide) microspheres in vivo and in vitro. Biomaterials. 1999; 20: 1057-1062.
77. Verspohl EJ. Novel therapeutics for type 2 diabetes: incretin hormone mimetics (glucagon-like peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors. Pharmacol Ther. 2009; 124: 113-118.
78. 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: 1487-1493.
79. Drucker DJ, Buse JB, Taylor K, et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, noninferiority study. Lancet. 2008; 372: 1240-1250.
80. Food and Drug Administration Center for Drug Evaluation and Research (CDER) Endocrinologic and Metabolic Drugs Advisory Committee Meeting. Hilton Hotel, Washington DC/Silver Spring, Maryland. Summary Minutes. 2009. Available at: www. fda. gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugs/AdvisoryCommittee/UCM192028. pdf. Accessed: January 28, 2011.
81. Lamari Y, Boissard C, Moukhtar MS, Jullienne A, Rosselin G, Garel JM. Expression of glucagonlike peptide 1 receptor in a murine C cell line: regulation of calcitonin gene by glucagon-like peptide 1. FEBS Lett. 1996; 393: 248-252.
82. Dore DD, Seeger JD, Arnold Chan K. Use of a claims-based active drug safety surveillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared to metformin or glyburide. Curr Med Res Opin. 2009; 25: 1019-1027.
83. Noel RA, Braun DK, Patterson RE, Bloomgren GL. Increased risk of acute pancreatitis and biliary disease observed in patients with type 2 diabetes: a retrospective cohort study. Diabetes Care. 2009; 32: 834-838.
84. Drucker J, Sherman SI, Gorelick FS, et al. Incretinbased therapies for the treatment of type 2 diabetes: evaluation of the risks and benefits. Diabetes Care. 2010; 33: 428-433.
85. Franklin I, Gromada J, Gjinovci A, Theander S, Wollheim CB. β-cell secretory products activate α-cell ATP-dependent potassium channels to inhibit glucagon release. Diabetes. 2005; 54: 1808-1815.
86. Moens K, Heimberg H, Flamez D, et al. Expression and functional activity of glucagon, glucagon-like peptide I, and glucose-dependent insulinotropic peptide receptors in rat pancreatic islet cells. Diabetes. 1996; 45: 257-261.