Addition of a dipeptidyl peptidase-4 inhibitor, sitagliptin, to ongoing therapy with the glucagon-like peptide-1 receptor agonist liraglutide: A randomized controlled trial in patients with type 2 diabetes

Diabetes, Obesity and Metabolism

Volumn 19, Issue 2, 2017, Pages 200-207

  Nauck, Michael A ^a   Kahle, Melanie ^a   Baranov, Oleg ^a   Deacon, Carolyn F ^b   Holst, Jens J ^b  

^a DIABETESZENTRUM BAD LAUTERBERG   (Germany)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

dipeptidyl peptidase 4 inhibitors; GLP 1 receptor agonists; glucagon secretion; incretin based diabetes medications; insulin secretion

Indexed keywords

C PEPTIDE; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON; GLUCAGON LIKE PEPTIDE 1; INCRETIN; INSULIN; LIRAGLUTIDE; METFORMIN; PLACEBO; SITAGLIPTIN; ANTIDIABETIC AGENT; DIPEPTIDYL PEPTIDASE IV INHIBITOR; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; GLUCOSE BLOOD LEVEL; GLYCOSYLATED HEMOGLOBIN; HEMOGLOBIN A1C PROTEIN, HUMAN;

ADULT; ARTICLE; CLINICAL ARTICLE; CLINICAL EFFECTIVENESS; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; FEMALE; GLUCAGON BLOOD LEVEL; GLYCEMIC CONTROL; HUMAN; INSULIN BLOOD LEVEL; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION; AGED; AGONISTS; COMBINATION DRUG THERAPY; DIABETES MELLITUS, TYPE 2; GLUCOSE BLOOD LEVEL; METABOLISM; MIDDLE AGED; TREATMENT OUTCOME;

ADULT; AGED; BLOOD GLUCOSE; C-PEPTIDE; CROSS-OVER STUDIES; DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; DRUG THERAPY, COMBINATION; FEMALE; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON; GLUCAGON-LIKE PEPTIDE 1; GLUCAGON-LIKE PEPTIDE-1 RECEPTOR; HEMOGLOBIN A, GLYCOSYLATED; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN; LIRAGLUTIDE; MALE; METFORMIN; MIDDLE AGED; SITAGLIPTIN PHOSPHATE; TREATMENT OUTCOME;

EID: 85001850036     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.12802     Document Type: Article

References (42)

1. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368:1696-1705.
2. Nauck MA, Meier JJ. Glucagon-like peptide 1 (GLP-1) and its derivatives in the treatment of diabetes. Regul Pept. 2005;124(suppl 1):135-148.
3. Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2012;8:728-742.
4. Åhren 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;27:2874-2880.
5. Vardarli I, Nauck MA, Köthe LD, et al. Inhibition of DPP-4 with vildagliptin improved insulin secretion in response to oral as well as “isoglycemic” intravenous glucose without numerically changing the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011;96:945-954.
6. Vardarli I, Arndt E, Deacon CF, Holst JJ, Nauck MA. Effects of sitagliptin and metformin treatment on incretin hormone and insulin secretory responses to oral and “isoglycemic” intravenous glucose. Diabetes. 2014;63:663-674.
7. Nauck MA, Kind J, Köthe LD, et al. Quantification of the contribution of GLP-1 to mediating insulinotropic effects of DPP-4 inhibition with vildagliptin in healthy subjects and patients with type 2 diabetes using exendin [9-39] as a GLP-1 receptor antagonist. Diabetes 2016;65:2440-2447.
8. Aulinger BA, Bedorf A, Kutscherauer G, et al. Defining the role of GLP-1 in the enteroinsulinar axis in type 2 diabetes using DPP-4 inhibition and GLP-1 receptor blockade. Diabetes. 2014;63:1079-1092.
9. Nauck MA, Heimesaat MM, Ørskov 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.
10. 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.
11. Mentlein R. Dipeptidyl-peptidase IV (CD26) – role in the inactivation of regulatory peptides. Regul Pept. 1999;85:9-24.
12. Filipsson K, Sundler F, Ahren B. PACAP is an islet neuropeptide which contributes to glucose-stimulated insulin secretion. Biochem Biophys Res Commun. 1999;256:664-667.
13. Pettersson M, Ahren B. Gastrin releasing peptide (GRP): effects on basal and stimulated insulin and glucagon secretion in the mouse. Peptides. 1987;8:55-60.
14. Violante R, Oliveira JH, Yoon KH, et al. A randomized non-inferiority study comparing the addition of exenatide twice daily to sitagliptin or switching from sitagliptin to exenatide twice daily in patients with type 2 diabetes experiencing inadequate glycaemic control on metformin and sitagliptin. Diabet Med. 2012;29:e417-e424.
15. Malm-Erjefält M, Bjornsdottir I, Vanggaard J, et al. Metabolism and excretion of the once-daily human glucagon-like peptide-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.
16. Nauck MA, Kahle M, Baranov O, Deacon CF, Holst JJ. Adding a DPP-4 inhibitor to ongoing therapy with a GLP-1 receptor agonist and metformin increases intact GLP-1, but does not change insulin or glucagon secretion nor plasma glucose excursions following a mixed test meal in patients with type 2 diabetes (abstract). Diabetes. 2015;64(suppl 1):A3.
17. Meier JJ, Gallwitz B, Salmen S, et al. Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous glucagon-like peptide 1 in patients with type 2 diabetes. J Clin Endocrinol Metab. 2003;88:2719-2725.
18. Hovorka R, Koukkou E, Southerden D, Powrie JK, Young MA. Measuring pre-hepatic insulin secretion using a population model of C-peptide kinetics: accuracy and required sampling schedule. Diabetologia. 1998;41:548-554.
19. 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;89:2078-2084.
20. Herman GA, Bergman A, Stevens C, et al. 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. 2006;91:4612-4619.
21. Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab. 2007;9:194-205.
22. Nauck MA, Ellis GC, Fleck PR, Wilson CA, Mekki Q. Efficacy and safety of adding the dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicentre, randomised, double-blind, placebo-controlled study. Int J Clin Pract. 2009;63:46-55.
23. Raz I, Chen Y, Wu M, et al. Efficacy and safety of sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes. Curr Med Res Opin. 2008;24:537-550.
24. Baranov O, Kahle M, Deacon CF, Holst JJ, Nauck MA. Feed-back suppression of meal-induced GLP-1 secretion mediated through elevations in intact GLP-1 caused by DPP-4 inhibition: a randomized, prospective comparison of sitagliptin and vildagliptin treatment. Diabetes Obes Metab. 2016;18:1100-1109.
25. Göke R, Fehmann HC, Linn T, et al. Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells. J Biol Chem. 1993;268:19650-19655.
26. Thorens B, Porret A, Buhler L, Deng SP, Morel P, Widmann C. 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.
27. Bjerre Knudsen L, Agerso H, Bjenning C, et al. GLP-1 derivatives as novel compounds for the treatment of type 2 diabetes: selection of NN2211 for clinical development. Drugs Future. 2001;26:677-685.
28. Aaboe K, Akram S, Deacon CF, Holst JJ, Madsbad S, Krarup T. Restoration of the insulinotropic effect of glucose-dependent insulinotropic polypeptide contributes to the antidiabetic effect of dipeptidyl peptidase-4 inhibitors. Diabetes Obes Metab. 2015;17:74-81.
29. Al-Sabah S, Al-Fulaij M, Ahmed HA. Selectivity of peptide ligands for the human incretin receptors expressed in HEK-293 cells. Eur J Pharmacol. 2014;741:311-315.
30. Deane AM, Nguyen NQ, Stevens JE, et al. Endogenous glucagon-like peptide-1 slows gastric emptying in healthy subjects, attenuating postprandial glycemia. J Clin Endocrinol Metabol. 2010;95:215-221.
31. Edwards CMB, Todd JF, Mahmoudi M, et al. GLP-1 has a physiological role in the control of postprandial glucose in man. Studies with the antagonist exendin 9-39. Diabetes. 1999;48:86-93.
32. Unniappan S, McIntosh CH, Demuth HU, Heiser U, Wolf R, Kieffer TJ. Effects of dipeptidyl peptidase IV on the satiety actions of peptide YY. Diabetologia. 2006;49:1915-1923.
33. Calara F, Taylor K, Han J, et al. A randomized, open-label, crossover study examining the effect of injection site on bioavailability of exenatide (synthetic exendin-4). Clin Ther. 2005;27:210-215.
34. 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.
35. Fonseca VA, Alvarado-Ruiz R, Raccah D, Boka G, Miossec P, Gerich JE. Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-Mono). Diabetes Care. 2012;35:1225-1231.
36. Rosenstock J, Raccah D, Koranyi L, et al. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin: a 24-week, randomized, open-label, active-controlled study (GetGoal-X). Diabetes Care. 2013;36:2945-2951.
37. Pyke C, Heller RS, Kirk RK, et al. GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology. 2014;155:1280-1290.
38. Deacon CF, Wamberg S, Bie P, Hughes TE, Holst JJ. Preservation of active incretin hormones by inhibition of dipeptidyl peptidase IV suppresses meal-induced incretin secretion in dogs. J Endocrinol. 2002;172:355-362.
39. Elbrønd B, Jakobsen G, Larsen S, et al. Pharmacokinetics, pharmacodynamics, safety, and tolerability of a single-dose of NN2211, a long-acting glucagon-like peptide 1 derivative, in healthy male subjects. Diabetes Care. 2002;25:1398-1404.
40. Agersø H, Jensen LB, Elbrond B, Rolan P, Zdravkovic M. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia. 2002;45:195-202.
41. Meier JJ, Rosenstock J, Hincelin-Mery A, et al. Contrasting effects of lixisenatide and liraglutide on postprandial glycemic control, gastric emptying, and safety parameters in patients with type 2 diabetes on optimized insulin glargine with or without metformin: a randomized, open-label trial. Diabetes Care. 2015;38:1263-1273.
42. Kapitza C, Forst T, Coester HV, Poitiers F, Ruus P, Hincelin-Mery A. Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insufficiently controlled on metformin. Diabetes Obes Metab. 2013;15:642-649.