• 1
    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;15:54059. Erratum in: Endocr Pract. 2009;15:768-70.
  • 2
    National Institute for Health and Clinical Excellence. Type 2 diabetes. The management of type 2 diabetes (update). London: Royal College of Physicians, 2008. Available from: (accessed 19 August 2010).
  • 3
    Pollack MF, Purayidathil FW, Bolge SC, Williams SA. Patient-reported tolerability issues with oral antidiabetic agents: associations with adherence; treatment satisfaction and health-related quality of life. Diabetes Res Clin Pract 2010; 87: 20410.
  • 4
    Carver C. Insulin treatment and the problem of weight gain in type 2 diabetes. Diabetes Educ 2006; 32: 9107.
  • 5
    Korytkowski M. When oral agents fail: practical barriers to starting insulin. Int J Obes Relat Metab Disord 2002; 26(Suppl. 3): S1824.
  • 6
    Gilbert M, Pratley R. Efficacy and safety of incretin therapies in patients with type 2 diabetes mellitus. Eur J Intern Med 2009; 20(Suppl. 2): S30918.
  • 7
    Mortensen K, Christensen LL, Holst JJ, Ørskov C. GLP-1 and GIP are colocalized in a subset of endocrine cells in the small intestine. Regul Pept 2003; 114: 18996.
  • 8
    Nauck M, Kleine N, Ørskov C et al. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993; 36: 7414.
  • 9
    Nauck M, El-Ouaghlidi A, Hompesch M, Jacobsen J, Elbrønd B. No impairment of hypoglycemia counterregulation via glucagon with NN2211, a GLP-1 derivative, in subjects with type 2-diabetes. Diabetes 2003; 52(Suppl. 1): A128.
  • 10
    Ørskov C, Holst J, Nielsen O. Effect of truncated glucagon-like peptide-1 [proglucagon-(78-107) amide] on endocrine secretion from pig pancreas, antrum and non-antral stomach. Endocrinology 1988; 123: 200913.
  • 11
    Degn K, Juhl C, Sturis J et al. One week’s treatment with the long-acting glucagon-like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and α- and β-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes 2004; 53: 118794.
  • 12
    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: 51520.
  • 13
    Willms B, Werner J, Holst JJ, Ørskov C, Creutzfeldt W, Nauck MA. Gastric emptying, glucose response, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(7-36) amide in type 2 (noninsulin-dependent) diabetic patients. J Clin Endocrinol Metab 1996; 81: 32732.
  • 14
    Nauck M, Niedereichholz U, Ettler R et al. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol 1997; 273: E9818.
  • 15
    Toft-Nielsen M, Damholt M, Madsbad S et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001; 86: 371723.
  • 16
    Nauck M, Stöckmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 1986; 29: 4652.
  • 17
    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: 11119.
  • 18
    Højberg PV, Zander M, Vilsbøll T et al. Near normalisation of blood glucose improves the potentiating effect of GLP-1 on glucose-induced insulin secretion in patients with type 2 diabetes. 2008; 51: 63240.
  • 19
    Mentlein R, Gallwitz B, Schmidt WE. Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem 1993; 214: 82935.
  • 20
    Vilsbøll T, Agersø H, Krarup T, Holst J. Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. J Clin Endocrinol Metab 2003; 88: 2204.
  • 21
    Vilsbøll T. Liraglutide: a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus. Expert Opin Investig Drugs 2007; 16: 2317.
  • 22
    Bjørnsdottir I, Olsen A, Larsen U et al. Metabolism and excretion of the once-daily human GLP-1 analogue liraglutide in healthy subject and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. Diabetologia 2008; 51(Suppl. 1): S356.
  • 23
    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: 1398404.
  • 24
    Agersø H, Jensen LB, Elbrønd 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: 195202.
  • 25
    Vilsbøll T, Zdravkovic M, Le-Thi T et al. Liraglutide, a long-acting human GLP-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes mellitus. Diabetes Care 2007; 30: 160810.
  • 26
    Flint A, Nazzal K, Jagielski P et al. Influence of hepatic impairment on pharmacokinetics of the long-acting human GLP-1 analogue liraglutide. Diabetes 2007; 56(Suppl. 1): A145.
  • 27
    Damholt B, Golor G, Wierich W et al. An open-label parallel-group study investigating the effects of age and gender on the pharmacokinetics of the once-daily glucagon-like peptide-1 analogue liraglutide. J Clin Pharmacol 2006; 46: 63541.
  • 28
    Malm-Erjefält M, Ekblom M, Brønsted L, Vouis J, Lennernäs H, Zdravkovic M. A randomised, double-blind, cross-over trial investigating the effect of liraglutide on the absorption pharmacokinetics of concomitantly administered oral drugs in healthy subjects. Diabetes 2008; 57(Suppl.1): A130.
  • 29
    Zdravkovic M, Ekblom M, Brønsted L, Vouis J, Lennernäs H, Malm-Erjefält M. The effect of liraglutide on the absorption pharmacokinetics of concomitant oral drugs with different solubility and permeability properties in healthy subjects. Diabetologia 2008; 51(Suppl. 1): S355.
  • 30
    Juhl C, Hollingdal M, Sturis J et al. Bedtime administration of NN2211, a long-acting GLP-1 derivative, substantially reduces fasting and postprandial glycemia in type 2 diabetes. Diabetes 2002; 51: 4249.
  • 31
    Harder H, Nielsen L, Thi T, Astrup A. The effect of liraglutide, a long-acting glucagon-like peptide 1 derivative, on glycemic control, body composition and 24-h energy expenditure in patients with type 2 diabetes. Diabetes Care 2004; 27: 191521.
  • 32
    Fava S. Role of postprandial hyperglycemia in cardiovascular disease. Expert Rev Cardiovasc Ther 2008; 6: 85972.
  • 33
    Flint A, Kapitza C, Hindsberger C, Zdravkovic M. The once-daily human GLP-1 analogue liraglutide improves both absolute and baseline corrected postprandial glucose levels. Diabetes 2008; 57(Suppl. 1): P556.
  • 34
    Mari A, Degn K, Brock B, Rungby J, Ferrannini E, Schmitz O. Effects of the long-acting human glucagon-like peptide-1 analog liraglutide on beta-cell function in normal living conditions. Diabetes Care 2007; 30: 20323.
  • 35
    Chang AM, Jakobsen G, Sturis J et al. The GLP-1 derivative NN2211 restores beta cell sensitivity to glucose in type 2 diabetic patients after a single dose. Diabetes 2003; 52: 178691.
  • 36
    Madsbad S, Schmitz O, Ranstam J, Jakobsen G, Matthews DR; NN2211-1310 International Study Group. 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 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial. Diabetes Care 2004; 27: 133542.
  • 37
    Ward WK, LaCava EC, Paquette TL, Beard JC, Wallum BJ, Porte D Jr. Disproportionate elevation of immunoreactive proinsulin in type 2 (non-insulin-dependent) diabetes mellitus and in experimental insulin resistance. Diabetologia 1987; 30: 698702.
  • 38
    Kahn SE, Halban PA. Release of incompletely processed proinsulin is the cause of the disproportionate proinsulinemia of NIDDM. Diabetes 1997; 46: 172532.
  • 39
    Ward W, Bolgiano D, McKnight B et al. Diminished B-cell secretory capacity in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1984; 74: 131828.
  • 40
    Vilsbøll T, Brock B, Perrild H et al. 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 2008; 25: 1526.
  • 41
    Shah P, Vella A, Basu A, Basu R, Schwenk WF, Rizza RA. Lack of suppression of glucagon contributes to postprandial hyperglycemia in subjects with type 2 diabetes mellitus. J Clin Endocrinol Metab 2000; 85: 40539.
  • 42
    Meier J, Kjems LL, Veldhuis JD, Lefe`bvre P, Butler PC. Postprandial suppression of glucagon secretion depends on intact pulsatile insulin secretion: further evidence for the intraislet insulin hypothesis. Diabetes 2006; 55: 10516.
  • 43
    Prazak R, Rütti S, Ellingsgaard H, Knudsen L, Donath MY. Liraglutide induces beta cell proliferation and protects from interleukin-1-beta induced beta cell apoptosis in human islets. Diabetologia 2008; 51(Suppl. 1): S2123.
  • 44
    Horowitz M, Flint A, Doran S et al. Effects of the once-daily human GLP-1 analogue liraglutide on appetite and energy intake in type 2 diabetes. Diabetologia 2008; 51(Suppl. 1): S355.
  • 45
    Nauck M, Hompesch M, Filipczak R et al. 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: 41723.
  • 46
    Marre M, Shaw J, Brandle M et al.; on behalf of the LEAD-1 SU study group. Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD-1 SU). Diabet Med 2009; 26: 26878.
  • 47
    Zinman B, Gerich J, Buse J et al.; LEAD-4 Study Investigators. 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: 122430.
  • 48
    Russell-Jones D, Vaag A, Schmitz O et al.; on behalf of the LEAD-5 (Liraglutide Effect and Action in Diabetes 5) met+SU Study Group. Liraglutide vs insulin glargine and placebo in combination with metformin and sulphonylurea therapy in type 2 diabetes mellitus: a randomised controlled trial (LEAD-5 met+SU). Diabetologia 2009; 52: 204655.
  • 49
    Ahren B. Emerging dipeptidyl peptidase-4 inhibitors for the treatment of diabetes. Expert Opin Emerg Drugs 2008; 13: 593607.
  • 50
    Feinglos MN, Saad MF, Pi-Sunyer FX, An B, Santiago O; Liraglutide Dose-Response Study Group. Effects of liraglutide (NN2211), a long-acting GLP-1 analogue, on glycaemic control and bodyweight in subjects with Type 2 diabetes. Diabet Med 2005; 22: 101623.
  • 51
    Courrèges JP, Vilsbøll T, Zdravkovic M et al. 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 2008; 25: 112931.