Emerging role of insulin with incretin therapies for management of type 2 diabetes

Diabetes Therapy

Volumn 2, Issue 3, 2011, Pages 146-161

  Ahluwalia, Rupa ^a   Vora, Jiten ^a  

^a ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST   (United Kingdom)

Author keywords

incretin therapy; insulin; treatment; type 2 diabetes mellitus

Indexed keywords

ALOGLIPTIN; ANTIDIABETIC AGENT; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EXENDIN 4; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; INCRETIN; INSULIN; INSULIN ASPART; INSULIN DETEMIR; INSULIN GLARGINE; INSULIN LISPRO; LIRAGLUTIDE; METFORMIN; ORAL ANTIDIABETIC AGENT; PLACEBO; SITAGLIPTIN; UNCLASSIFIED DRUG; VILDAGLIPTIN;

ACUTE PANCREATITIS; ADD ON THERAPY; ANTIBODY PRODUCTION; COMBINATION CHEMOTHERAPY; DIARRHEA; DISEASE COURSE; DOSAGE SCHEDULE COMPARISON; DRUG DOSE TITRATION; DRUG HYPERSENSITIVITY; DRUG INDICATION; DRUG MEGADOSE; DRUG SAFETY; GASTROINTESTINAL SYMPTOM; HUMAN; HYPERGLYCEMIA; HYPOGLYCEMIA; INJECTION SITE PRURITUS; INJECTION SITE RASH; INSULIN TREATMENT; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; VOMITING; WEIGHT CHANGE; WEIGHT GAIN;

EID: 80052822199     PISSN: 18696953     EISSN: 18696961     Source Type: Journal    
DOI: 10.1007/s13300-011-0005-0     Document Type: Review

References (69)

1. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. 2004; 88: 787-835.
2. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycaemia 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. Diabetologia. 2009; 52: 17-30.
3. Holman R. Metformin as first choice in oral diabetes treatment: the UKPDS experience. J Annu Diabetol Hotel Dieu. 2007: 13-20.
4. Hermansen K, Mortensen LS. Bodyweight changes associated with antihyperglycaemic agents in type 2 diabetes mellitus. Drug Saf. 2007; 30: 1127-1142.
5. 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.
6. Nauck M, Stockmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulindependent) diabetes. Diabetologia. 1986; 29: 46-52.
7. 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: 301-307.
8. 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.
9. Meier JJ, Nauck MA. Is the diminished incretin effect in type 2 diabetes just an epi-phenomenon of impaired beta-cell function? Diabetes. 2010; 59: 1117-1125.
10. Ahrén B, Schweizer A, Dejager S, et al. Vildagliptin enhances islet responsiveness to both hyper- and hypoglycemia in patients with type 2 diabetes. J Clin Endocrinol Metab. 2009; 94: 1236-1243.
11. Degn KB, Brock B, Juhl CB, et al. Effect of intravenous infusion of exenatide (synthetic exendin-4) on glucose-dependent insulin secretion and counter regulation during hypoglycemia. Diabetes. 2004; 53: 2397-2403.
12. Wettergren A, Schjoldager B, Mortensen PE, Myhre J, Christiansen J, Holst JJ. Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci. 1993; 38: 665-673.
13. 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: 515-520.
14. Mudaliar S, Henry RR. Effects of incretin hormones on beta cell mass and function, body weight, and hepatic and myocardial function. Am J Med. 2010; 123(Suppl. 3): S19-27.
15. Tews D, Werner U, Eckel J. Enhanced protection against cytokine- and fatty acid-induced apoptosis in pancreatic beta cells by combined treatment with glucagon-like peptide-1 receptor agonists and insulin analogues. Horm Metab Res. 2008; 40: 172-180.
16. Bosi E. Time for testing incretin therapies in early type 1 diabetes? J Clin Endocrinol Metab. 2010; 95: 2607-2609.
17. Drucker DJ. The biology of incretin hormones. Cell Metab 2006; 3: 153-165.
18. Nauck MA, Heimesaat MM, Behle K, et al. Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycaemic clamp experiments in healthy volunteers. J Clin Endocrinol Metab. 2002; 87: 1239-1246.
19. Chaudhri O, Small C, Bloom S. Gastrointestinal hormones regulating appetite. Philos Trans R Soc Lond B Biol Sci. 2006; 361: 1187-1209.
20. Barber TM, Begbie H, Levy J. The incretin pathway as a new therapeutic target for obesity. Maturitas. 2010; 67: 197-202.
21. 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: CD006739.
22. Bell TJ and Wright EE Jr. Can therapies that target the incretin system improve our ability to treat type 2 diabetes? J Natl Med Assoc. 2010; 102: 511-523.
23. Neumiller JJ. Clinical pharmacology of incretin therapies for type 2 diabetes mellitus: implications for treatment. Clin Ther. 2011; 33: 528-576.
24. 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.
25. Victoza (liraglutide [rDNA] injection) [prescribing information]. Princeton, New Jersey: Novo Nordisk Inc; 2011. Available at: http://www. novo-pi. com/ victoza. pdf. Last accessed June 7, 2011.
26. Hegedüs L, Moses AC, Zdravkovic M, Le Thi T, Daniels GH. GLP-1 and calcitonin concentration in humans: lack of evidence of calcitonin release from sequential screening in over 5000 subjects with type 2 diabetes or nondiabetic obese subjects treated with the human GLP-1 analog, liraglutide. J Clin Endocrinol Metab. 2011; 96: 853-860.
27. Heine RJ, van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RG. Exenatide versus insulin glargine in patients with sub optimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2005; 143: 559-569.
28. 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 study. Diabetologia. 2007; 50: 259-267.
29. Russell-Jones D, Vaag A, Schmitz O, et al. 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.
30. Diamant M, van Gaal L, Stranks S, et al. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet. 2010; 375: 2234-2243.
31. Type 2 diabetes-newer agents for blood glucose control in type 2 diabetes (partial update of CG66). National Institute for Health and Clinical Excellence (NICE). Short clinical guidance 87. May 2009.
32. Coates PA, Ollerton RL, Luzio SD, Ismail I, Owens DR. A glimpse of the 'natural history' of established type 2 (non-insulin dependent) diabetes mellitus from the spectrum of metabolic and hormonal responses to a mixed meal at the time of diagnosis. Diabetes Res Clin Pract. 1994; 26: 177-187.
33. Owens DR, Luzio SD, Coates PA. Insulin secretion and sensitivity in newly diagnosed NIDDM Caucasians in the UK. Diabet Med. 1996; 13(9 Suppl. 6): S19-24.
34. Dunning BE, Foley JE, Ahrén B. Alpha cell function in health and disease: influence of glucagon-like peptide-1. Diabetologia. 2005; 48: 1700-1713.
35. Ahrén B. Beta- and alpha-cell dysfunction in subjects developing impaired glucose tolerance: outcome of a 12-year prospective study in postmenopausal Caucasian women. Diabetes. 2009; 58: 726-731.
36. Ahrén B, Foley JE, Ferrannini E, et al. Changes in prandial glucagon levels after a 2-year treatment with vildagliptin or glimepiride in patients with type 2 diabetes inadequately controlled with metformin monotherapy. Diabetes Care. 2010; 33: 730-732.
37. Holman RR, Thorne KI, Farmer AJ, et al. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med. 2007; 357: 1716-1730.
38. Holman RR, Farmer AJ, Davies MJ, et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009; 361: 1736-47.
39. Meneghini L, Liebl A, Abrahamson MJ. Insulin detemir: a historical perspective on a modern basal insulin analogue. Prim Care Diabetes. 2010; 4(Suppl. 1): S31-42.
40. Garvey WT, Olefsky JM, Griffin J, Hamman RF, Kolterman OG. The effect of insulin treatment on insulin secretion and insulin action in type II diabetes mellitus. Diabetes. 1985; 34: 222-234.
41. Li Y, Xu W, Liao Z, et al. Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients is associated with improvement of beta-cell function. Diabetes Care. 2004; 27: 2597-602.
42. Russell-Jones D, Khan R. Insulin-associated weight gain in diabetes - causes, effects and coping strategies. Diabetes Obes Metab. 2007; 9: 799-812.
43. Ahrén B. Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin. Vasc Health Risk Manag. 2008; 4: 383-394.
44. Mannucci E, Tesi F, Bardini G, et al. Effects of metformin on glucagon-like peptide-1 levels in obese patients with and without Type 2 diabetes. Diabetes Nutr Metab. 2004; 17: 336-342.
45. Migoya EM, Miller J, Larson P, et al. Sitagliptin, a selective DPP-4 inhibitor, and metformin have complementary effects to increase active GLP-1 concentrations. Diabetes. 2007; 56(Suppl. 1): A74.
46. Green BD, Irwin N, Duffy NA, Gault VA, O'Harte FP, Flatt PR. Inhibition of dipeptidyl peptidase-IV activity by metformin enhances the antidiabetic effects of glucagon-like peptide-1. Eur J Pharmacol. 2006; 547: 192-199.
47. Cuthbertson J, Patterson S, O'Harte FP, Bell PM. Addition of metformin to exogenous glucagonlike peptide-1 results in increased serum glucagonlike peptide-1 concentrations and greater glucose lowering in type 2 diabetes mellitus. Metabolism. 2011; 60: 52-56. Epub 2010 Feb 11.
48. Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE; 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: 1979-1987.
49. Jadzinsky M, Pfützner A, Paz-Pacheco E, Xu Z, Allen E, Chen R; CV181-039 Investigators. Saxagliptin given in combination with metformin as initial therapy improves glycemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diabetes Obes Metab. 2009; 11: 611-622.
50. Yoon NM, Cavaghan MK, Brunelle RL, Roach P. Exenatide added to insulin therapy: a retrospective review of clinical practice over two years in an academic endocrinology outpatient setting. Clin Ther. 2009; 31: 1511-1523.
51. Buse JB, Bergenstal RM, Glass LC, et al. Use of twice-daily exenatide in basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med. 2011; 154: 103-112.
52. Fonseca V, Schweizer A, Albrecht D, Baron MA, Chang I, Dejager S. Addition of vildagliptin to insulin improves glycemic control in type 2 diabetes. Diabetologia. 2007; 50: 1148-1155.
53. Rosenstock J, Rendell MS, Gross JL, Fleck PR, Wilson CA, Mekki Q. Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA1C without causing weight gain or increased hypoglycemia. Diabetes Obes Metab. 2009; 11: 1145-1152.
54. Vilsboll T, Rosenstock J, Yki-Jarvinen H, et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab. 2010; 12: 167-177.
55. Arnolds S, Dellweg S, Clair J, et al. Further improvement in postprandial glucose control with addition of exenatide or sitagliptin to combination therapy with insulin glargine and metformin: a proof-of-concept study. Diabetes Care. 2010; 33: 1509-1515.
56. Riddle M, Ahmann A, Basu A, Aroda V, Ratner R. Metformin+exenatide+basal insulin vs. metformin+placebo+basal insulin: reaching a1c & 6. 5% without weight-gain or serious hypoglycaemia (abstract). Diabetes. 2010; 59(Suppl. 1A): LB18.
57. Blevins TC, Arakaki RF, Liljenquist DR et al. Oncedaily basal insulin added to oral antihyperglycemic medications (OAMs) and exenatide (Ex) improves glycaemic control in patients (Pts) with type 2 diabetes (T2D)(abstract). Diabetes. 2010; 59(Suppl. 1A): LB19.
58. Asmar M, Højberg PV, Deacon CF, Hare K, Holst JJ, Madsbad S. Pancreatic beta-cell responses to GLP-1 after near-normalization of blood glucose in patients with type 2 diabetes. Regul Pept. 2010; 160: 175-180.
59. Pratley RE, Nauck M, Bailey T, et al. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet. 2010; 375: 1447-1456.
60. Bergenstal RM, Wysham C, Macconell L, et al. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet. 2010; 376: 431-439.
61. Malm-Erjefält M, Bjornsdottir I, Vanggaard J, et al. Metabolism and excretion of the once daily human GLP-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. Drug Metab Dispos. 2010; 38: 1944-1953.
62. Baggio LL, Kim JG, Drucker DJ. Chronic exposure to GLP-1R agonists promotes homologous GLP-1 receptor desensitization in vitro but does not attenuate GLP-1R-dependent glucose homeostasis in vivo. Diabetes. 2004; 53(Suppl. 3): S205-214.
63. Nauck MA, Kemmeries G, Holst JJ, Meier JJ. Rapid tachyphylaxis of the glucagon-like peptide-1-induced deceleration of gastric emptying in humans. Diabetes. 2011; 60: 1561-1565.
64. Buse JB, Garber A, Rosenstock J, et al. Liraglutide treatment is associated with a low frequency and magnitude of antibody formation with no apparent impact on glycemic response or increased frequency of adverse events: results from the Liraglutide Effect and Action in Diabetes (LEAD) trials. J Clin Endocrinol Metab. 2011; 96: 1695-1702.
65. 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.
66. Foley JE, Ligueros-Saylan M, He YL, et al. Effect of vildagliptin on glucagon concentration during meals in patients with type 1 diabetes. Horm Metab Res. 2008; 40: 727-730.
67. Fonseca V, Baron M, Shao Q, Dejager S. Sustained efficacy and reduced hypoglycemia during one year of treatment with vildagliptin added to insulin in patients with type 2 diabetes mellitus. Horm Metab Res. 2008; 40: 427-430.
68. Levin P, Mersey JH, Zhou S, Bromberger L. Clinical outcomes using single vs. combination therapy with glargine (GLA) or exenatide (EX)(abstract). Diabetes. 2010; 59(Suppl. 1): P652.
69. Hollander P, Raslova K, Skjoth TV, Råstam J, Liutkus JF. Efficacy and safety of insulin detemir once daily in combination with sitagliptin and metformin: the TRANSITION randomised controlled trial. Diabetes Obes Metab. 2011; 13: 268-275.