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Erschienen in: Pediatric Nephrology 7/2010

01.07.2010 | Review

The evolving place of incretin-based therapies in type 2 diabetes

verfasst von: Baptist Gallwitz

Erschienen in: Pediatric Nephrology | Ausgabe 7/2010

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Abstract

Treatment options for type 2 diabetes based on the action of the incretin hormone glucagon-like peptide-1 (GLP-1) were first introduced in 2005. These comprise the injectable GLP-1 receptor agonists solely acting on the GLP-1 receptor on the one hand and orally active dipeptidyl-peptidase inhibitors (DPP-4 inhibitors) raising endogenous GLP-1 and other hormone levels by inhibiting the degrading enzyme DPP-4. In adult medicine, both treatment options are attractive and more commonly used because of their action and safety profile. The incretin-based therapies stimulate insulin secretion and inhibit glucagon secretion in a glucose-dependent manner and carry no intrinsic risk of hypoglycaemia. GLP-1 receptor agonists allow weight loss, whereas DPP-4 inhibitors are weight neutral. This review gives an overview of the mechanism of action and the substances and clinical data available.
Literatur
2.
Zurück zum Zitat Zeitler P (2009) Update on nonautoimmune diabetes in children. J Clin Endocrinol Metab 94:2215–2220PubMedCrossRef Zeitler P (2009) Update on nonautoimmune diabetes in children. J Clin Endocrinol Metab 94:2215–2220PubMedCrossRef
3.
Zurück zum Zitat Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O (2003) Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348:383–393PubMedCrossRef Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O (2003) Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348:383–393PubMedCrossRef
4.
Zurück zum Zitat Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA (2008) 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 359:1577–1589PubMedCrossRef Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA (2008) 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 359:1577–1589PubMedCrossRef
5.
Zurück zum Zitat Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, Zinman B (2006) 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 49:1711–1721PubMedCrossRef Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, Zinman B (2006) 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 49:1711–1721PubMedCrossRef
6.
Zurück zum Zitat Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368:1696–1705PubMedCrossRef Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368:1696–1705PubMedCrossRef
7.
Zurück zum Zitat Wellendorph P, Johansen LD, Brauner-Osborne H (2009) Molecular pharmacology of promiscuous seven transmembrane receptors sensing organic nutrients. Mol Pharmacol 76:453–465PubMedCrossRef Wellendorph P, Johansen LD, Brauner-Osborne H (2009) Molecular pharmacology of promiscuous seven transmembrane receptors sensing organic nutrients. Mol Pharmacol 76:453–465PubMedCrossRef
9.
Zurück zum Zitat Nauck M, Stockmann F, Ebert R, Creutzfeldt W (1986) Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29:46–52PubMedCrossRef Nauck M, Stockmann F, Ebert R, Creutzfeldt W (1986) Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29:46–52PubMedCrossRef
10.
Zurück zum Zitat Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W (1993) 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 91:301–307PubMedCrossRef Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W (1993) 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 91:301–307PubMedCrossRef
11.
Zurück zum Zitat Vollmer K, Gardiwal H, Menge BA, Goetze O, Deacon CF, Schmidt WE, Holst JJ, Meier JJ (2009) Hyperglycemia acutely lowers the postprandial excursions of glucagon-like Peptide-1 and gastric inhibitory polypeptide in humans. J Clin Endocrinol Metab 94:1379–1385PubMedCrossRef Vollmer K, Gardiwal H, Menge BA, Goetze O, Deacon CF, Schmidt WE, Holst JJ, Meier JJ (2009) Hyperglycemia acutely lowers the postprandial excursions of glucagon-like Peptide-1 and gastric inhibitory polypeptide in humans. J Clin Endocrinol Metab 94:1379–1385PubMedCrossRef
12.
Zurück zum Zitat Nauck MA, Kleine N, Orskov C, Holst JJ, Willms B, Creutzfeldt W (1993) Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7–36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36:741–744PubMedCrossRef Nauck MA, Kleine N, Orskov C, Holst JJ, Willms B, Creutzfeldt W (1993) Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7–36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36:741–744PubMedCrossRef
13.
Zurück zum Zitat Brubaker PL, Drucker DJ (2004) Minireview: glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system. Endocrinology 145:2653–2659PubMedCrossRef Brubaker PL, Drucker DJ (2004) Minireview: glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system. Endocrinology 145:2653–2659PubMedCrossRef
14.
Zurück zum Zitat Fehmann HC, Habener JF (1992) Insulinotropic hormone glucagon-like peptide-I(7–37) stimulation of proinsulin gene expression and proinsulin biosynthesis in insulinoma beta TC-1 cells. Endocrinology 130:159–166PubMedCrossRef Fehmann HC, Habener JF (1992) Insulinotropic hormone glucagon-like peptide-I(7–37) stimulation of proinsulin gene expression and proinsulin biosynthesis in insulinoma beta TC-1 cells. Endocrinology 130:159–166PubMedCrossRef
15.
Zurück zum Zitat Courreges JP, Vilsboll T, Zdravkovic M, Le-Thi T, Krarup T, Schmitz O, Verhoeven R, Buganova I, Madsbad S (2008) Beneficial effects of once-daily liraglutide, a human glucagon-like peptide-1 analogue, on cardiovascular risk biomarkers in patients with Type 2 diabetes. Diabet Med 25:1129–1131PubMedCrossRef Courreges JP, Vilsboll T, Zdravkovic M, Le-Thi T, Krarup T, Schmitz O, Verhoeven R, Buganova I, Madsbad S (2008) Beneficial effects of once-daily liraglutide, a human glucagon-like peptide-1 analogue, on cardiovascular risk biomarkers in patients with Type 2 diabetes. Diabet Med 25:1129–1131PubMedCrossRef
16.
Zurück zum Zitat Klonoff DC, Buse JB, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, Wintle ME, Maggs DG (2008) 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 24:275–286PubMed Klonoff DC, Buse JB, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, Wintle ME, Maggs DG (2008) 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 24:275–286PubMed
17.
Zurück zum Zitat Sokos GG, Nikolaidis LA, Mankad S, Elahi D, Shannon RP (2006) Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail 12:694–699PubMedCrossRef Sokos GG, Nikolaidis LA, Mankad S, Elahi D, Shannon RP (2006) Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail 12:694–699PubMedCrossRef
18.
Zurück zum Zitat Yang J, Campitelli J, Hu G, Lin Y, Luo J, Xue C (2007) Increase in DPP-IV in the intestine, liver and kidney of the rat treated with high fat diet and streptozotocin. Life Sci 81:272–279PubMedCrossRef Yang J, Campitelli J, Hu G, Lin Y, Luo J, Xue C (2007) Increase in DPP-IV in the intestine, liver and kidney of the rat treated with high fat diet and streptozotocin. Life Sci 81:272–279PubMedCrossRef
19.
Zurück zum Zitat Lee Y, Kwon MK, Kang ES, Park YM, Choi SH, Ahn CW, Kim KS, Park CW, Cha BS, Kim SW, Sung JK, Lee EJ, Lee HC (2008) Adenoviral vector-mediated glucagon-like peptide 1 gene therapy improves glucose homeostasis in Zucker diabetic fatty rats. J Gene Med 10:260–268PubMedCrossRef Lee Y, Kwon MK, Kang ES, Park YM, Choi SH, Ahn CW, Kim KS, Park CW, Cha BS, Kim SW, Sung JK, Lee EJ, Lee HC (2008) Adenoviral vector-mediated glucagon-like peptide 1 gene therapy improves glucose homeostasis in Zucker diabetic fatty rats. J Gene Med 10:260–268PubMedCrossRef
20.
Zurück zum Zitat Gallwitz B (2006) Exenatide in type 2 diabetes: treatment effects in clinical studies and animal study data. Int J Clin Pract 60:1654–1661PubMedCrossRef Gallwitz B (2006) Exenatide in type 2 diabetes: treatment effects in clinical studies and animal study data. Int J Clin Pract 60:1654–1661PubMedCrossRef
21.
Zurück zum Zitat Eng J, Kleinman WA, Singh L, Singh G, Raufman JP (1992) 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 267:7402–7405PubMed Eng J, Kleinman WA, Singh L, Singh G, Raufman JP (1992) 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 267:7402–7405PubMed
22.
Zurück zum Zitat Gedulin BR, Smith P, Prickett KS, Tryon M, Barnhill S, Reynolds J, Nielsen LL, Parkes DG, Young AA (2005) Dose-response for glycaemic and metabolic changes 28 days after single injection of long-acting release exenatide in diabetic fatty Zucker rats. Diabetologia 48:1380–1385PubMedCrossRef Gedulin BR, Smith P, Prickett KS, Tryon M, Barnhill S, Reynolds J, Nielsen LL, Parkes DG, Young AA (2005) Dose-response for glycaemic and metabolic changes 28 days after single injection of long-acting release exenatide in diabetic fatty Zucker rats. Diabetologia 48:1380–1385PubMedCrossRef
23.
Zurück zum Zitat Kim D, MacConell L, Zhuang D, Kothare PA, Trautmann M, Fineman M, Taylor K (2007) 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 30:1487–1493PubMedCrossRef Kim D, MacConell L, Zhuang D, Kothare PA, Trautmann M, Fineman M, Taylor K (2007) 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 30:1487–1493PubMedCrossRef
24.
Zurück zum Zitat Drucker DJ, Buse JB, Taylor K, Kendall DM, Trautmann M, Zhuang D, Porter L (2008) Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet 372:1240–1250PubMedCrossRef Drucker DJ, Buse JB, Taylor K, Kendall DM, Trautmann M, Zhuang D, Porter L (2008) Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet 372:1240–1250PubMedCrossRef
25.
Zurück zum Zitat McGill JB (2009) Insights from the liraglutide clinical development program—the Liraglutide Effect and Action in Diabetes (LEAD) studies. Postgrad Med 121:16–25PubMedCrossRef McGill JB (2009) Insights from the liraglutide clinical development program—the Liraglutide Effect and Action in Diabetes (LEAD) studies. Postgrad Med 121:16–25PubMedCrossRef
26.
Zurück zum Zitat Agerso H, Jensen LB, Elbrond B, Rolan P, Zdravkovic M (2002) The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia 45:195–202PubMedCrossRef Agerso H, Jensen LB, Elbrond B, Rolan P, Zdravkovic M (2002) The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia 45:195–202PubMedCrossRef
27.
Zurück zum Zitat Chang AM, Jakobsen G, Sturis J, Smith MJ, Bloem CJ, An B, Galecki A, Halter JB (2003) The GLP-1 derivative NN2211 restores beta-cell sensitivity to glucose in type 2 diabetic patients after a single dose. Diabetes 52:1786–1791PubMedCrossRef Chang AM, Jakobsen G, Sturis J, Smith MJ, Bloem CJ, An B, Galecki A, Halter JB (2003) The GLP-1 derivative NN2211 restores beta-cell sensitivity to glucose in type 2 diabetic patients after a single dose. Diabetes 52:1786–1791PubMedCrossRef
28.
Zurück zum Zitat Retterstol K (2009) Taspoglutide: a long acting human glucagon-like polypeptide-1 analogue. Expert Opin Investig Drugs 18:1405–1411PubMedCrossRef Retterstol K (2009) Taspoglutide: a long acting human glucagon-like polypeptide-1 analogue. Expert Opin Investig Drugs 18:1405–1411PubMedCrossRef
29.
Zurück zum Zitat Werner U (2008) Preclinical pharmacology of the new GLP-1 receptor agonist AVE0010. Ann Endocrinol (Paris) 69:164–165 Werner U (2008) Preclinical pharmacology of the new GLP-1 receptor agonist AVE0010. Ann Endocrinol (Paris) 69:164–165
30.
Zurück zum Zitat Rosenstock J, Reusch J, Bush M, Yang F, Stewart M (2009) The 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 32:1880–1886PubMedCrossRef Rosenstock J, Reusch J, Bush M, Yang F, Stewart M (2009) The 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 32:1880–1886PubMedCrossRef
31.
32.
Zurück zum Zitat Kolterman OG, Kim DD, Shen L, Ruggles JA, Nielsen LL, Fineman MS, Baron AD (2005) Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am J Health Syst Pharm 62:173–181PubMed Kolterman OG, Kim DD, Shen L, Ruggles JA, Nielsen LL, Fineman MS, Baron AD (2005) Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am J Health Syst Pharm 62:173–181PubMed
33.
Zurück zum Zitat DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD (2005) Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 28:1092–1100PubMedCrossRef DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD (2005) Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 28:1092–1100PubMedCrossRef
34.
Zurück zum Zitat Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD (2004) Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 27:2628–2635PubMedCrossRef Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD (2004) Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 27:2628–2635PubMedCrossRef
35.
Zurück zum Zitat Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, Baron AD (2005) Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 28:1083–1091PubMedCrossRef Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, Baron AD (2005) Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 28:1083–1091PubMedCrossRef
36.
Zurück zum Zitat Heine RJ, van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RG (2005) Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 143:559–569PubMed Heine RJ, van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RG (2005) Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 143:559–569PubMed
37.
Zurück zum Zitat Nauck MA, Duran S, Kim D, Johns D, Northrup J, Festa A, Brodows R, Trautmann M (2007) 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 50:259–267PubMedCrossRef Nauck MA, Duran S, Kim D, Johns D, Northrup J, Festa A, Brodows R, Trautmann M (2007) 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 50:259–267PubMedCrossRef
38.
Zurück zum Zitat Zinman B, Hoogwerf BJ, Duran Garcia S, Milton DR, Giaconia JM, Kim DD, Trautmann ME, Brodows RG (2007) The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 146:477–485PubMed Zinman B, Hoogwerf BJ, Duran Garcia S, Milton DR, Giaconia JM, Kim DD, Trautmann ME, Brodows RG (2007) The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 146:477–485PubMed
39.
Zurück zum Zitat Barnett AH, Burger J, Johns D, Brodows R, Kendall DM, Roberts A, Trautmann ME (2007) 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, open-label, two-period, crossover noninferiority trial. Clin Ther 29:2333–2348PubMedCrossRef Barnett AH, Burger J, Johns D, Brodows R, Kendall DM, Roberts A, Trautmann ME (2007) 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, open-label, two-period, crossover noninferiority trial. Clin Ther 29:2333–2348PubMedCrossRef
41.
Zurück zum Zitat Bunck MC, Diamant M, Corner A, Eliasson B, Malloy JL, Shaginian RM, Deng W, Kendall DM, Taskinen MR, Smith U, Yki-Jarvinen H, Heine RJ (2009) One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care 32:762–768PubMedCrossRef Bunck MC, Diamant M, Corner A, Eliasson B, Malloy JL, Shaginian RM, Deng W, Kendall DM, Taskinen MR, Smith U, Yki-Jarvinen H, Heine RJ (2009) One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care 32:762–768PubMedCrossRef
42.
Zurück zum Zitat Ahmad SR, Swann J (2008) Exenatide and rare adverse events. N Engl J Med 358:1970–1971PubMed Ahmad SR, Swann J (2008) Exenatide and rare adverse events. N Engl J Med 358:1970–1971PubMed
43.
Zurück zum Zitat Cure P, Pileggi A, Alejandro R (2008) Exenatide and rare adverse events. N Engl J Med 358:1969–1970PubMedCrossRef Cure P, Pileggi A, Alejandro R (2008) Exenatide and rare adverse events. N Engl J Med 358:1969–1970PubMedCrossRef
44.
Zurück zum Zitat Dore DD, Seeger JD, Arnold Chan K (2009) 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 25:1019–1027PubMedCrossRef Dore DD, Seeger JD, Arnold Chan K (2009) 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 25:1019–1027PubMedCrossRef
45.
Zurück zum Zitat Yoo BK, Triller DM, Yoo DJ (2006) Exenatide: a new option for the treatment of type 2 diabetes. Ann Pharmacother 40:1777–1784PubMedCrossRef Yoo BK, Triller DM, Yoo DJ (2006) Exenatide: a new option for the treatment of type 2 diabetes. Ann Pharmacother 40:1777–1784PubMedCrossRef
47.
Zurück zum Zitat Malloy J, Capparelli E, Gottschalk M, Guan X, Kothare P, Fineman M (2009) Pharmacology and tolerability of a single dose of exenatide in adolescent patients with type 2 diabetes mellitus being treated with metformin: a randomized, placebo-controlled, single-blind, dose-escalation, crossover study. Clin Ther 31:806–815PubMedCrossRef Malloy J, Capparelli E, Gottschalk M, Guan X, Kothare P, Fineman M (2009) Pharmacology and tolerability of a single dose of exenatide in adolescent patients with type 2 diabetes mellitus being treated with metformin: a randomized, placebo-controlled, single-blind, dose-escalation, crossover study. Clin Ther 31:806–815PubMedCrossRef
48.
Zurück zum Zitat Sturis J, Gotfredsen CF, Romer J, Rolin B, Ribel U, Brand CL, Wilken M, Wassermann K, Deacon CF, Carr RD, Knudsen LB (2003) GLP-1 derivative liraglutide in rats with beta-cell deficiencies: influence of metabolic state on beta-cell mass dynamics. Br J Pharmacol 140:123–132PubMedCrossRef Sturis J, Gotfredsen CF, Romer J, Rolin B, Ribel U, Brand CL, Wilken M, Wassermann K, Deacon CF, Carr RD, Knudsen LB (2003) GLP-1 derivative liraglutide in rats with beta-cell deficiencies: influence of metabolic state on beta-cell mass dynamics. Br J Pharmacol 140:123–132PubMedCrossRef
49.
Zurück zum Zitat Garber A, Klein E, Bruce S, Sankoh S, Mohideen P (2006) Metformin-glibenclamide versus metformin plus rosiglitazone in patients with type 2 diabetes inadequately controlled on metformin monotherapy. Diabetes Obes Metab 8:156–163PubMedCrossRef Garber A, Klein E, Bruce S, Sankoh S, Mohideen P (2006) Metformin-glibenclamide versus metformin plus rosiglitazone in patients with type 2 diabetes inadequately controlled on metformin monotherapy. Diabetes Obes Metab 8:156–163PubMedCrossRef
50.
Zurück zum Zitat Garber AJ, Spann SJ (2008) An overview of incretin clinical trials. J Fam Pract 57(Suppl):S10–S18PubMed Garber AJ, Spann SJ (2008) An overview of incretin clinical trials. J Fam Pract 57(Suppl):S10–S18PubMed
51.
Zurück zum Zitat Nauck MA, Ratner RE, Kapitza C, Berria R, Boldrin M, Balena R (2009) 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 32:1237–1243PubMedCrossRef Nauck MA, Ratner RE, Kapitza C, Berria R, Boldrin M, Balena R (2009) 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 32:1237–1243PubMedCrossRef
52.
Zurück zum Zitat Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, During M, Matthews DR (2009) 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 32:84–90PubMedCrossRef Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, During M, Matthews DR (2009) 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 32:84–90PubMedCrossRef
53.
Zurück zum Zitat Marre M, Shaw J, Brandle M, Bebakar WM, Kamaruddin NA, Strand J, Zdravkovic M, Le Thi TD, Colagiuri S (2009) 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 26:268–278PubMedCrossRef Marre M, Shaw J, Brandle M, Bebakar WM, Kamaruddin NA, Strand J, Zdravkovic M, Le Thi TD, Colagiuri S (2009) 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 26:268–278PubMedCrossRef
54.
Zurück zum Zitat Zinman B, Gerich J, Buse JB, Lewin A, Schwartz S, Raskin P, Hale PM, Zdravkovic M, Blonde L (2009) 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 32:1224–1230PubMedCrossRef Zinman B, Gerich J, Buse JB, Lewin A, Schwartz S, Raskin P, Hale PM, Zdravkovic M, Blonde L (2009) 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 32:1224–1230PubMedCrossRef
55.
Zurück zum Zitat Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, Hale PM, Zdravkovic M, Bode B (2008) Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet 373:473–481PubMedCrossRef Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, Hale PM, Zdravkovic M, Bode B (2008) Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet 373:473–481PubMedCrossRef
56.
Zurück zum Zitat Garber A, Henry RR, Ratner RE, Hale P, Chang CT, Bode B (2009) Monotherapy with liraglutide, a once-daily human GLP-1 analog, provides sustained reductions in A1C, FPG, and weight compared with glimepiride in type 2 diabetes: LEAD-3 mono 2-year results. Diabetes 58(Suppl 1):162, OR Garber A, Henry RR, Ratner RE, Hale P, Chang CT, Bode B (2009) Monotherapy with liraglutide, a once-daily human GLP-1 analog, provides sustained reductions in A1C, FPG, and weight compared with glimepiride in type 2 diabetes: LEAD-3 mono 2-year results. Diabetes 58(Suppl 1):162, OR
57.
Zurück zum Zitat Deacon CF (2009) Potential of liraglutide in the treatment of patients with type 2 diabetes. Vasc Health Risk Manag 5:199–211PubMed Deacon CF (2009) Potential of liraglutide in the treatment of patients with type 2 diabetes. Vasc Health Risk Manag 5:199–211PubMed
58.
Zurück zum Zitat Vilsboll T (2009) Liraglutide: a new treatment for type 2 diabetes. Drugs Today (Barc) 45:101–113 Vilsboll T (2009) Liraglutide: a new treatment for type 2 diabetes. Drugs Today (Barc) 45:101–113
59.
Zurück zum Zitat Nauck M, Marre M (2009) Adding liraglutide to oral antidiabetic drug monotherapy: efficacy and weight benefits. Postgrad Med 121:5–15PubMedCrossRef Nauck M, Marre M (2009) Adding liraglutide to oral antidiabetic drug monotherapy: efficacy and weight benefits. Postgrad Med 121:5–15PubMedCrossRef
60.
Zurück zum Zitat Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L (2009) Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 374:39–47PubMedCrossRef Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L (2009) Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 374:39–47PubMedCrossRef
61.
Zurück zum Zitat Vilsboll T, Brock B, Perrild H, Levin K, Lervang HH, Kolendorf K, Krarup T, Schmitz O, Zdravkovic M, Le-Thi T, Madsbad S (2008) Liraglutide, a once-daily human GLP-1 analogue, improves pancreatic B-cell function and arginine-stimulated insulin secretion during hyperglycaemia in patients with Type 2 diabetes mellitus. Diabet Med 25:152–156PubMedCrossRef Vilsboll T, Brock B, Perrild H, Levin K, Lervang HH, Kolendorf K, Krarup T, Schmitz O, Zdravkovic M, Le-Thi T, Madsbad S (2008) Liraglutide, a once-daily human GLP-1 analogue, improves pancreatic B-cell function and arginine-stimulated insulin secretion during hyperglycaemia in patients with Type 2 diabetes mellitus. Diabet Med 25:152–156PubMedCrossRef
62.
Zurück zum Zitat Ahren B (2008) Emerging dipeptidyl peptidase-4 inhibitors for the treatment of diabetes. Expert Opin Emerg Drugs 13:593–607PubMedCrossRef Ahren B (2008) Emerging dipeptidyl peptidase-4 inhibitors for the treatment of diabetes. Expert Opin Emerg Drugs 13:593–607PubMedCrossRef
63.
Zurück zum Zitat Mest HJ (2006) Dipeptidyl peptidase-IV inhibitors can restore glucose homeostasis in type 2 diabetics via incretin enhancement. Curr Opin Investig Drugs 7:338–343PubMed Mest HJ (2006) Dipeptidyl peptidase-IV inhibitors can restore glucose homeostasis in type 2 diabetics via incretin enhancement. Curr Opin Investig Drugs 7:338–343PubMed
64.
Zurück zum Zitat Gallwitz B (2008) Saxagliptin, a dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. IDrugs 12:906–917 Gallwitz B (2008) Saxagliptin, a dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. IDrugs 12:906–917
65.
Zurück zum Zitat Pratley RE, Reusch JE, Fleck PR, Wilson CA, Mekki Q (2009) Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Curr Med Res Opin 25:2361–2371PubMedCrossRef Pratley RE, Reusch JE, Fleck PR, Wilson CA, Mekki Q (2009) Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Curr Med Res Opin 25:2361–2371PubMedCrossRef
66.
Zurück zum Zitat Heise T, Graefe-Mody EU, Huttner S, Ring A, Trommeshauser D, Dugi KA (2009) Pharmacokinetics, pharmacodynamics and tolerability of multiple oral doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients. Diabetes Obes Metab 11:786–794PubMedCrossRef Heise T, Graefe-Mody EU, Huttner S, Ring A, Trommeshauser D, Dugi KA (2009) Pharmacokinetics, pharmacodynamics and tolerability of multiple oral doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients. Diabetes Obes Metab 11:786–794PubMedCrossRef
67.
Zurück zum Zitat Pratley RE (2008) Overview of glucagon-like peptide-1 analogs and dipeptidyl peptidase-4 inhibitors for type 2 diabetes. Medscape J Med 10:171PubMed Pratley RE (2008) Overview of glucagon-like peptide-1 analogs and dipeptidyl peptidase-4 inhibitors for type 2 diabetes. Medscape J Med 10:171PubMed
68.
Zurück zum Zitat Barnett AH (2009) New treatments in type 2 diabetes: a focus on the incretin-based therapies. Clin Endocrinol (Oxf) 70:343–353CrossRef Barnett AH (2009) New treatments in type 2 diabetes: a focus on the incretin-based therapies. Clin Endocrinol (Oxf) 70:343–353CrossRef
69.
Zurück zum Zitat Karasik A, Aschner P, Katzeff H, Davies MJ, Stein PP (2008) Sitagliptin, a DPP-4 inhibitor for the treatment of patients with type 2 diabetes: a review of recent clinical trials. Curr Med Res Opin 24:489–496PubMedCrossRef Karasik A, Aschner P, Katzeff H, Davies MJ, Stein PP (2008) Sitagliptin, a DPP-4 inhibitor for the treatment of patients with type 2 diabetes: a review of recent clinical trials. Curr Med Res Opin 24:489–496PubMedCrossRef
70.
Zurück zum Zitat Green J, Feinglos M (2008) New combination treatments in the management of diabetes: focus on sitagliptin-metformin. Vasc Health Risk Manag 4:743–751PubMed Green J, Feinglos M (2008) New combination treatments in the management of diabetes: focus on sitagliptin-metformin. Vasc Health Risk Manag 4:743–751PubMed
71.
Zurück zum Zitat Williams-Herman D, Round E, Swern AS, Musser B, Davies MJ, Stein PP, Kaufman KD, Amatruda JM (2008) Safety and tolerability of sitagliptin in patients with type 2 diabetes: a pooled analysis. BMC Endocr Disord 8:14PubMedCrossRef Williams-Herman D, Round E, Swern AS, Musser B, Davies MJ, Stein PP, Kaufman KD, Amatruda JM (2008) Safety and tolerability of sitagliptin in patients with type 2 diabetes: a pooled analysis. BMC Endocr Disord 8:14PubMedCrossRef
72.
Zurück zum Zitat Herman GA, Bergman A, Yi B, Kipnes M (2006) Tolerability and pharmacokinetics of metformin and the dipeptidyl peptidase-4 inhibitor sitagliptin when co-administered in patients with type 2 diabetes. Curr Med Res Opin 22:1939–1947PubMedCrossRef Herman GA, Bergman A, Yi B, Kipnes M (2006) Tolerability and pharmacokinetics of metformin and the dipeptidyl peptidase-4 inhibitor sitagliptin when co-administered in patients with type 2 diabetes. Curr Med Res Opin 22:1939–1947PubMedCrossRef
73.
Zurück zum Zitat Herman GA, Bergman A, Liu F, Stevens C, Wang AQ, Zeng W, Chen L, Snyder K, Hilliard D, Tanen M, Tanaka W, Meehan AG, Lasseter K, Dilzer S, Blum R, Wagner JA (2006) Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. J Clin Pharmacol 45:876–886 Herman GA, Bergman A, Liu F, Stevens C, Wang AQ, Zeng W, Chen L, Snyder K, Hilliard D, Tanen M, Tanaka W, Meehan AG, Lasseter K, Dilzer S, Blum R, Wagner JA (2006) Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. J Clin Pharmacol 45:876–886
74.
Zurück zum Zitat Herman GA, Bergman A, Stevens C, Kotey P, Yi B, Zhao P, Dietrich B, Golor G, Schrodter A, Keymeulen B, Lasseter KC, Kipnes MS, Snyder K, Hilliard D, Tanen M, Cilissen C, De Smet M, de Lepeleire I, Van Dyck K, Wang AQ, Zeng W, Davies MJ, Tanaka W, Holst JJ, Deacon CF, Gottesdiener KM, Wagner JA (2006) Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes. J Clin Endocrinol Metab 91:4612–4619PubMedCrossRef Herman GA, Bergman A, Stevens C, Kotey P, Yi B, Zhao P, Dietrich B, Golor G, Schrodter A, Keymeulen B, Lasseter KC, Kipnes MS, Snyder K, Hilliard D, Tanen M, Cilissen C, De Smet M, de Lepeleire I, Van Dyck K, Wang AQ, Zeng W, Davies MJ, Tanaka W, Holst JJ, Deacon CF, Gottesdiener KM, Wagner JA (2006) Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes. J Clin Endocrinol Metab 91:4612–4619PubMedCrossRef
75.
Zurück zum Zitat Scott R, Wu M, Sanchez M, Stein P (2007) Efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy over 12 weeks in patients with type 2 diabetes. Int J Clin Pract 61:171–180PubMedCrossRef Scott R, Wu M, Sanchez M, Stein P (2007) Efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy over 12 weeks in patients with type 2 diabetes. Int J Clin Pract 61:171–180PubMedCrossRef
76.
Zurück zum Zitat Chan JC, Scott R, Arjona Ferreira JC, Sheng D, Gonzalez E, Davies MJ, Stein PP, Kaufman KD, Amatruda JM, Williams-Herman D (2008) Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency. Diabetes Obes Metab 10:545–555PubMedCrossRef Chan JC, Scott R, Arjona Ferreira JC, Sheng D, Gonzalez E, Davies MJ, Stein PP, Kaufman KD, Amatruda JM, Williams-Herman D (2008) Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency. Diabetes Obes Metab 10:545–555PubMedCrossRef
77.
Zurück zum Zitat Ahren B (2008) Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin. Vasc Health Risk Manag 4:383–394PubMed Ahren B (2008) Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin. Vasc Health Risk Manag 4:383–394PubMed
78.
Zurück zum Zitat Ahren B, Foley JE (2008) The islet enhancer vildagliptin: mechanisms of improved glucose metabolism. Int J Clin Pract Suppl 175:8–14CrossRef Ahren B, Foley JE (2008) The islet enhancer vildagliptin: mechanisms of improved glucose metabolism. Int J Clin Pract Suppl 175:8–14CrossRef
79.
Zurück zum Zitat Pratley RE, Rosenstock J, Pi-Sunyer FX, Banerji MA, Schweizer A, Couturier A, Dejager S (2007) Management of type 2 diabetes in treatment-naive elderly patients: benefits and risks of vildagliptin monotherapy. Diabetes Care 30:3017–3022PubMedCrossRef Pratley RE, Rosenstock J, Pi-Sunyer FX, Banerji MA, Schweizer A, Couturier A, Dejager S (2007) Management of type 2 diabetes in treatment-naive elderly patients: benefits and risks of vildagliptin monotherapy. Diabetes Care 30:3017–3022PubMedCrossRef
80.
Zurück zum Zitat Rosenstock J, Sankoh S, List JF (2008) Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab 10:376–386PubMedCrossRef Rosenstock J, Sankoh S, List JF (2008) Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab 10:376–386PubMedCrossRef
81.
Zurück zum Zitat Rosenstock J, Aguilar-Salinas C, Klein E, Nepal S, List J, Chen R (2009) Effect of saxagliptin monotherapy in treatment-naive patients with type 2 diabetes. Curr Med Res Opin 25:2401–2411PubMedCrossRef Rosenstock J, Aguilar-Salinas C, Klein E, Nepal S, List J, Chen R (2009) Effect of saxagliptin monotherapy in treatment-naive patients with type 2 diabetes. Curr Med Res Opin 25:2401–2411PubMedCrossRef
82.
Zurück zum Zitat Deacon CF, Holst JJ (2009) Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. Adv Ther 26:488–499PubMedCrossRef Deacon CF, Holst JJ (2009) Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. Adv Ther 26:488–499PubMedCrossRef
83.
Zurück zum Zitat Tahrani AA, Piya MK, Barnett AH (2009) Saxagliptin: a new DPP-4 inhibitor for the treatment of type 2 diabetes mellitus. Adv Ther 26:249–262PubMedCrossRef Tahrani AA, Piya MK, Barnett AH (2009) Saxagliptin: a new DPP-4 inhibitor for the treatment of type 2 diabetes mellitus. Adv Ther 26:249–262PubMedCrossRef
84.
Zurück zum Zitat Chacra AR, Tan GH, Apanovitch A, Ravichandran S, List J, Chen R (2009) Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial. Int J Clin Pract 63:1395–1406PubMedCrossRef Chacra AR, Tan GH, Apanovitch A, Ravichandran S, List J, Chen R (2009) Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial. Int J Clin Pract 63:1395–1406PubMedCrossRef
85.
Zurück zum Zitat DeFronzo RA, Hissa MN, Garber AJ, Luiz Gross J, Yuyan Duan R, Ravichandran S, Chen RS (2009) The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diabetes Care 32:1649–1655PubMedCrossRef DeFronzo RA, Hissa MN, Garber AJ, Luiz Gross J, Yuyan Duan R, Ravichandran S, Chen RS (2009) The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diabetes Care 32:1649–1655PubMedCrossRef
86.
Zurück zum Zitat Wolf R, Frederich R, Fiedorek FT, Donovan M, Xu Z, Harris S, Chen R (2009) Evaluation of CV risk in the saxagliptin clinical trials. Diabetes 59(Suppl 1):8, LB Wolf R, Frederich R, Fiedorek FT, Donovan M, Xu Z, Harris S, Chen R (2009) Evaluation of CV risk in the saxagliptin clinical trials. Diabetes 59(Suppl 1):8, LB
87.
Zurück zum Zitat Matthaei S, Bierwirth R, Fritsche A, Gallwitz B, Häring HU, Joost HG, Kellerer M, Kloos C, Kunt T, Nauck MA, Schernthaner G, Siegel E, Thienel F (2009) Medicinal antihyperglycemic therapy of type 2 diabetes. Guidelines of the German Diabetes Association. Exp Clin Endocrinol Diabetes 117:522–557PubMedCrossRef Matthaei S, Bierwirth R, Fritsche A, Gallwitz B, Häring HU, Joost HG, Kellerer M, Kloos C, Kunt T, Nauck MA, Schernthaner G, Siegel E, Thienel F (2009) Medicinal antihyperglycemic therapy of type 2 diabetes. Guidelines of the German Diabetes Association. Exp Clin Endocrinol Diabetes 117:522–557PubMedCrossRef
89.
Zurück zum Zitat Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV (2009) Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 301:1565–1572PubMedCrossRef Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV (2009) Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 301:1565–1572PubMedCrossRef
90.
Zurück zum Zitat Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP (2007) 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 9:194–205PubMedCrossRef Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP (2007) 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 9:194–205PubMedCrossRef
91.
Zurück zum Zitat Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT (2008) Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358:2545–2559PubMedCrossRef Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT (2008) Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358:2545–2559PubMedCrossRef
92.
Zurück zum Zitat Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B (2009) Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 32:193–203PubMedCrossRef Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B (2009) Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care 32:193–203PubMedCrossRef
93.
Zurück zum Zitat Vilsboll T, Rosenstock J, Yki-Jarvinen H, Cefalu WT, Chen Y, Ling Y, Meehan AG, Katz L, Engel SS, Kaufman KD, Amatruda JM (2009) Sitagliptin, a selective DPP-4 inhibitor, improves glycemic control when added to insulin, with or without metformin, in patients with type 2. Diabetes 58(Suppl 1):588, P Vilsboll T, Rosenstock J, Yki-Jarvinen H, Cefalu WT, Chen Y, Ling Y, Meehan AG, Katz L, Engel SS, Kaufman KD, Amatruda JM (2009) Sitagliptin, a selective DPP-4 inhibitor, improves glycemic control when added to insulin, with or without metformin, in patients with type 2. Diabetes 58(Suppl 1):588, P
94.
Zurück zum Zitat Fonseca V, Baron M, Shao Q, Dejager S (2008) 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 40:427–430PubMedCrossRef Fonseca V, Baron M, Shao Q, Dejager S (2008) 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 40:427–430PubMedCrossRef
95.
Zurück zum Zitat Perry T, Holloway HW, Weerasuriya A, Mouton PR, Duffy K, Mattison JA, Greig NH (2007) Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy. Exp Neurol 203:293–301PubMedCrossRef Perry T, Holloway HW, Weerasuriya A, Mouton PR, Duffy K, Mattison JA, Greig NH (2007) Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy. Exp Neurol 203:293–301PubMedCrossRef
96.
Zurück zum Zitat Müssig K, Oncu A, Lindauer P, Heininger A, Aebert H, Unertl K, Ziemer G, Häring HU, Holst JJ, Gallwitz B (2008) 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 102:646–647PubMedCrossRef Müssig K, Oncu A, Lindauer P, Heininger A, Aebert H, Unertl K, Ziemer G, Häring HU, Holst JJ, Gallwitz B (2008) 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 102:646–647PubMedCrossRef
97.
Zurück zum Zitat Nikolaidis LA, Elahi D, Hentosz T, Doverspike A, Huerbin R, Zourelias L, Stolarski C, Shen YT, Shannon RP (2004) Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy. Circulation 110:955–961PubMedCrossRef Nikolaidis LA, Elahi D, Hentosz T, Doverspike A, Huerbin R, Zourelias L, Stolarski C, Shen YT, Shannon RP (2004) Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy. Circulation 110:955–961PubMedCrossRef
98.
Zurück zum Zitat Nikolaidis LA, Doverspike A, Hentosz T, Zourelias L, Shen YT, Elahi D, Shannon RP (2005) Glucagon-like peptide-1 limits myocardial stunning following brief coronary occlusion and reperfusion in conscious canines. J Pharmacol Exp Ther 312:303–308PubMedCrossRef Nikolaidis LA, Doverspike A, Hentosz T, Zourelias L, Shen YT, Elahi D, Shannon RP (2005) Glucagon-like peptide-1 limits myocardial stunning following brief coronary occlusion and reperfusion in conscious canines. J Pharmacol Exp Ther 312:303–308PubMedCrossRef
99.
Zurück zum Zitat Nikolaidis LA, Elahi D, Shen YT, Shannon RP (2005) Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 289:H2401–H2408PubMedCrossRef Nikolaidis LA, Elahi D, Shen YT, Shannon RP (2005) Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 289:H2401–H2408PubMedCrossRef
100.
Zurück zum Zitat Carraro-Lacroix LR, Malnic G, Girardi AC (2009) Regulation of Na+/H+ exchanger NHE3 by the glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells. Am J Physiol Renal Physiol 297:F1647–F1655PubMedCrossRef Carraro-Lacroix LR, Malnic G, Girardi AC (2009) Regulation of Na+/H+ exchanger NHE3 by the glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells. Am J Physiol Renal Physiol 297:F1647–F1655PubMedCrossRef
101.
Zurück zum Zitat Schlatter P, Beglinger C, Drewe J, Gutmann H (2007) Glucagon-like peptide 1 receptor expression in primary porcine proximal tubular cells. Regul Pept 141:120–128PubMedCrossRef Schlatter P, Beglinger C, Drewe J, Gutmann H (2007) Glucagon-like peptide 1 receptor expression in primary porcine proximal tubular cells. Regul Pept 141:120–128PubMedCrossRef
102.
Zurück zum Zitat Hirata K, Kume S, Araki S, Sakaguchi M, Chin-Kanasaki M, Isshiki K, Sugimoto T, Nishiyama A, Koya D, Haneda M, Kashiwagi A, Uzu T (2009) Exendin-4 has an anti-hypertensive effect in salt-sensitive mice model. Biochem Biophys Res Commun 380:44–49PubMedCrossRef Hirata K, Kume S, Araki S, Sakaguchi M, Chin-Kanasaki M, Isshiki K, Sugimoto T, Nishiyama A, Koya D, Haneda M, Kashiwagi A, Uzu T (2009) Exendin-4 has an anti-hypertensive effect in salt-sensitive mice model. Biochem Biophys Res Commun 380:44–49PubMedCrossRef
103.
Zurück zum Zitat Meier JJ, Nauck MA, Kranz D, Holst JJ, Deacon CF, Gaeckler D, Schmidt WE, Gallwitz B (2004) Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects. Diabetes 53:654–662PubMedCrossRef Meier JJ, Nauck MA, Kranz D, Holst JJ, Deacon CF, Gaeckler D, Schmidt WE, Gallwitz B (2004) Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects. Diabetes 53:654–662PubMedCrossRef
104.
Zurück zum Zitat Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132:2131–2457PubMedCrossRef Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132:2131–2457PubMedCrossRef
105.
Zurück zum Zitat Farilla L, Bulotta A, Hirshberg B, Li Calzi S, Khoury N, Noushmehr H, Bertolotto C, Di Mario U, Harlan DM, Perfetti R (2003) Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology 144:5149–5158PubMedCrossRef Farilla L, Bulotta A, Hirshberg B, Li Calzi S, Khoury N, Noushmehr H, Bertolotto C, Di Mario U, Harlan DM, Perfetti R (2003) Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology 144:5149–5158PubMedCrossRef
106.
Zurück zum Zitat Waldron-Lynch F, von Herrath M, Herold KC (2008) Towards a curative therapy in type 1 diabetes: remission of autoimmunity, maintenance and augmentation of beta cell mass. Novartis Found Symp 292:146–155PubMedCrossRef Waldron-Lynch F, von Herrath M, Herold KC (2008) Towards a curative therapy in type 1 diabetes: remission of autoimmunity, maintenance and augmentation of beta cell mass. Novartis Found Symp 292:146–155PubMedCrossRef
107.
Zurück zum Zitat Raman VS, Heptulla RA (2009) New potential adjuncts to treatment of children with type 1 diabetes mellitus. Pediatr Res 65:370–374PubMedCrossRef Raman VS, Heptulla RA (2009) New potential adjuncts to treatment of children with type 1 diabetes mellitus. Pediatr Res 65:370–374PubMedCrossRef
108.
Zurück zum Zitat Creutzfeldt WO, Kleine N, Willms B, Orskov C, Holst JJ, Nauck MA (1996) Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide I(7–36) amide in type I diabetic patients. Diabetes Care 19:580–586PubMedCrossRef Creutzfeldt WO, Kleine N, Willms B, Orskov C, Holst JJ, Nauck MA (1996) Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide I(7–36) amide in type I diabetic patients. Diabetes Care 19:580–586PubMedCrossRef
Metadaten
Titel
The evolving place of incretin-based therapies in type 2 diabetes
verfasst von
Baptist Gallwitz
Publikationsdatum
01.07.2010
Verlag
Springer-Verlag
Erschienen in
Pediatric Nephrology / Ausgabe 7/2010
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-009-1435-z

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