The design of the liraglutide clinical trial programme

Diabetes, Obesity and Metabolism

Volumn 14, Issue SUPPL. 2, 2012, Pages 4-12

  Nauck, M A ^a  

^a DIABETESZENTRUM BAD LAUTERBERG   (Germany)

Author keywords

Efficacy; GLP 1; Liraglutide; Safety; Treatment guidelines

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; C PEPTIDE; CALCITONIN; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EXENDIN 4; GLIMEPIRIDE; GLIPIZIDE; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 DERIVATIVE; GLUCOSE; HEMOGLOBIN A1C; INSULIN; INSULIN DETEMIR; INSULIN GLARGINE; LIRAGLUTIDE; METFORMIN; PLACEBO; PROINSULIN; ROSIGLITAZONE; SAXAGLIPTIN; SITAGLIPTIN; SULFONYLUREA DERIVATIVE; VILDAGLIPTIN;

ANTIDIABETIC ACTIVITY; CARDIOVASCULAR RISK; CLINICAL EXAMINATION; COMPARATIVE STUDY; DIET RESTRICTION; DISEASE DURATION; DRUG APPROVAL; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; ELECTROCARDIOGRAM; GLUCOSE BLOOD LEVEL; GLYCEMIC CONTROL; HUMAN; HYPOGLYCEMIA; INSULIN RELEASE; METHODOLOGY; MONOTHERAPY; NON INSULIN DEPENDENT DIABETES MELLITUS; OUTCOME ASSESSMENT; PANCREAS ISLET BETA CELL; PANCREATITIS; PHASE 3 CLINICAL TRIAL (TOPIC); PRACTICE GUIDELINE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK ASSESSMENT; RISK REDUCTION; SUSTAINED RELEASE FORMULATION; TREATMENT DURATION; TREATMENT INDICATION; WEIGHT GAIN;

EID: 84858143648     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/j.1463-1326.2012.01573.x     Document Type: Review

References (68)

1. Madsbad S, Schmitz O, Ranstam J, Jakobsen G, Matthews DR. Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analogue liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial. Diabetes Care 2004; 27: 1335-1342.
2. Nauck MA, Hompesch M, Filipczak R, Le TD, Zdravkovic M, Gumprecht J. Five weeks of treatment with the GLP-1 analogue liraglutide improves glycaemic control and lowers body weight in subjects with type 2 diabetes. Exp Clin Endocrinol Diabetes 2006; 114: 417-423.
3. Vilsbøll T, Zdravkovic M, Le-Thi T et al. Liraglutide, a long-acting human glucagon-like peptide-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes. Diabetes Care 2007; 30: 1608-1610.
4. Nathan DM, Buse JB, Davidson MB, American Diabetes Association et al. European Association for Study of Diabetes. Medical management of hyperglycemia 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. Diabetes Care 2009; 32: 193-203.
5. Gough SCL. Liraglutide: from clinical trials to clinical practice. Diabetes Obes Metab 2012; 14(Suppl. 2): 33-40.
6. Rodbard HW, Jellinger PS, Davidson JA et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract 2009; 15: 540-549.
7. Holman R. Long-term efficacy of sulfonylureas: a United Kingdom Prospective Diabetes Study perspective. Metabolism 2006; 55(Suppl. 1): S2-S5.
8. UK Prospective Study Group. Overview of six years' therapy of type 2 diabetes-a progressive disease (UKPDS 16). Diabetes.1995; 44: 1249-1258.
9. Garber A, Henry R, Ratner R et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet 2009; 373: 473-481.
10. Marre M, Shaw J, Brändle M, LEAD-1 SU Study Group et al. Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 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.
11. Nauck M, Frid A, Hermansen K, LEAD-2 Study Group et al., Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin in type 2 diabetes Diabetes Care 2009; 32: 84-90.
12. Zinman B, Gerich J, Buse JB et al. Efficacy and safety of the human GLP-1 analog liraglutide in combination with metformin and TZD in patients with type 2 diabetes mellitus (LEAD-4 Met+TZD). Diabetes Care. 2009; 32: 1224-1230.
13. 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.
14. Buse J, Rosenstock J, Sesti G, for the LEAD 6 Study Group et al. 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 2009; 374: 39-47.
15. Pratley RE, Nauck M, Bailey T, 1860-LIRA-DPP-4 Study Group et al. 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.
16. Knudsen LB, Madsen L, Jacobsen S et al. Glucagon-like peptide-1 receptor agonists activate rodent, but not human, thyroid C-cells causing calcitonin release and proliferation. Presented at the 80th Annual Meeting of the American Thyroid Association. 23-27 September 2009, Palm Beach, FL, USA.
17. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man Diabetologia 1985; 28: 412-419.
18. Novo Nordisk A/S. Victoza® (liraglutide) European SPC. Available from URL Accessed 30September 2011.
19. Novo Nordisk, Inc. Victoza® (liraglutide) US label. Available from URL Accessed 28 September 2011.
20. Novo Nordisk, Inc. Levemir® (insulin detemir) European SPC. Available from URL Accessed 14 November 2011.
21. Eli Lilly Nederland B.V. Byetta® (exenatide) European SPC. Available from URL Accessed 19 August 2011.
22. Amylin Pharmaceuticals, Inc. Byetta® (exenatide) US PI. Available from URL Accessed 30 October 2011.
23. Merck & Co., Inc. Januvia® (sitagliptin) European PI. Available from URL Accessed 28 September 2011.
24. Novartis AG. Galvus® (vildagliptin) European PI. Available from URL Accessed 28 September 2011.
25. Bristol-Myers Squibb Company. Onglyza® (saxagliptin) European PI. Available from URL Accessed 28 September 2011.
26. UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-853.
27. Brown JB, Nichols GA, Perry A. The burden of treatment failure in type 2 diabetes. Diabetes Care 2004; 27: 1535-1540.
28. Garber AJ. Liraglutide in oral antidiabetic drug combination therapy. Diabetes Obes Metab 2012; 14(Suppl. 2): 13-19.
29. Riddle MC, Rosenstock J, Gerich J, Insulin Glargine 4002 Study Investigators. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003; 26: 3080-3086.
30. Hermansen K, Davies M, Derezinski T, Martinez Ravn G, Clauson P, Home P. A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetes Care 2006; 29: 1269-1274.
31. Kendall DM, Riddle MC, Rosenstock J et al. 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 2005; 28: 1083-1091.
32. Heine RJ, Van Gaal LF, Johns D, GWAA Study Group et al. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 2005; 143: 559-569.
33. Blonde L, Montanya E. Comparison of liraglutide vs. other incretin-related anti-hyperglycaemic agents. Diabetes Obes Metab 2012; 14(Suppl. 2): 20-32.
34. Buse JB, Sesti G, Schmidt WE, Liraglutide Effect Action in Diabetes-6 Study Group 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.
35. Pratley R, Nauck M, Bailey T, 1860-LIRA-DPP-4 Study Group et al. One year of liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin, both in combination with metformin, in patients with type 2 diabetes: a randomised, parallel-group, open-label trial. Int J Clin Pract 2011; 65: 397-407.
36. Pratley R, Nauck M, Bailey T, for the 1860-Lira-DPP-4 Study Group et al. Switching from the DPP-4 inhibitor sitagliptin to the human GLP-1 analog liraglutide further improves glycemic control and weight loss in patients with type 2 diabetes. Diabetes 2011; 60(Suppl. 1): A307.
37. 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.
38. Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD, Exenatide-113 Clinical Study Group. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004; 27: 2628-2635.
39. Ratner RE, Maggs D, Nielsen LL et al. Long-term effects of exenatide therapy over 82 weeks on glycaemic control and weight in over-weight metformin-treated patients with type 2 diabetes mellitus. Diabetes Obes Metab 2006; 8: 419-428.
40. Blonde L, Klein EJ, Han J et al. Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab 2006; 8: 436-437.
41. 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.
42. 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, open-label, two-period, crossover noninferiority trial. Clin Ther 2007; 29: 2333-2348.
43. 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.
44. Davies MJ, Donnelly R, Barnett AH, Jones S, Nicolay C, Kilcoyne A. Exenatide compared with long-acting insulin to achieve glycaemic control with minimal weight gain in patients with type 2 diabetes: results of the Helping Evaluate Exenatide in patients with diabetes compared with Long-Acting insulin (HEELA) study. Diabetes Obes Metab. 2009; 11: 1153-1162.
45. Drucker DJ, Buse JB, Taylor K, DURATION-1 Study Group et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study Lancet 2008; 372: 1240-1250.
46. Bergenstal RM, Wysham C, Macconell L, DURATION-2 Study Group 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.
47. 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.
48. Blevins T, Pullman J, Malloy J et al. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endo Metab 2011; 96: 1301-1310.
49. Buse JB, Nauck MA, Forst T et al. Efficacy and safety of exenatide once weekly versus liraglutide in subjects with type 2 diabetes (DURATION-6): a randomised, open-label study. Diabetologia 2001; 54(Suppl. 1): S38.
50. Raz I, Hanefeld M, Xu L, et al., Sitagliptin Study 023 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia 2006; 49: 2564-2571.
51. Aschner P, Kipnes MS, Lunceford JK, Sitagliptin Study 021 Group et al. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 2006; 29: 2632-2637.
52. Charbonnel B, Karasik A, Liu J, Wu M, Meininger G, Sitagliptin Study 020 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care 2006; 29: 2638-2643.
53. Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P, Sitagliptin Study 019 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther 2006; 28: 1556-1568.
54. Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP, Sitagliptin Study 024 Group. 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.
55. Foley JE, Sreenan S. Efficacy and safety comparison between the DPP-4 inhibitor vildagliptin and the sulfonylurea gliclazide after two years of monotherapy in drug-naÏve patients with type 2 diabetes. Horm Metab Res 2009; 41: 905-909.
56. Bosi E, Dotta F, Jia Y, Goodman M. Vildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitus. Diabetes Obes Metab 2009; 11: 506-515.
57. Ferrannini E, Fonseca V, Zinman B et al. Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapy. Diabetes Obes Metab 2009; 11: 157-166.
58. Göke B, Hershon K, Kerr D et al. Efficacy and safety of vildagliptin monotherapy during 2-year treatment of drug-naÏve patients with type 2 diabetes: comparison with metformin. Horm Metab Res 2008; 40: 892-895.
59. Pan C, Yang W, Barona JP et al. Comparison of vildagliptin and acarbose monotherapy in patients with Type 2 diabetes: a 24-week, double-blind, randomized trial. Diabet Med 2008; 25: 435-441.
60. Bolli G, Dotta F, Rochotte E, Cohen SE. Efficacy and tolerability of vildagliptin vs. pioglitazone when added to metformin: a 24-week, randomized, double-blind study. Diabetes Obes Metab 2008; 10: 82-90.
61. Filozof C, Gautier JF. A comparison of efficacy and safety of vildagliptin and gliclazide in combination with metformin in patients with Type 2 diabetes inadequately controlled with metformin alone: a 52-week, randomized study. Diabet Med 2010; 27: 318-326.
62. Hollander P, Li J, Allen E, Chen R, CV181-013 Investigators. Saxagliptin added to a thiazolidinedione improves glycemic control in patients with type 2 diabetes and inadequate control on thiazolidinedione alone. J Clin Endocrinol Metab 2009; 94: 4810-4819.
63. Chacra AR, Tan GH, Apanovitch A, Ravichandran S, List J, Chen R, CV181-040 Investigators. 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 2009; 63: 1395-1406.
64. DeFronzo RA, Hissa MN, Garber AJ, Saxagliptin 014 Study Group et al. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diabetes Care 2009; 32: 1649-1655.
65. Rosenstock J, Sankoh S, List JF. Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab 2008; 10: 376-386.
66. 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 glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diabetes Obes Metab 2009; 11: 611-622.
67. Scheen AJ, Charpentier G, Ostgren CJ, Hellqvist A, Gause-Nilsson I. Efficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus. Diabetes Metab Res Rev 2010; 26: 540-549.
68. Owens DR, Swallow R, Dugi KA, Woerle HJ. Efficacy and safety of linagliptin in persons with Type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24-week randomized study Diabet Med 2011; 28: 1352-1361.