Cited by 700

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Potent Derivatives of Glucagon-like Peptide-1 with Pharmacokinetic Properties Suitable for Once Daily Administration

Open access

Knudsen, Lotte B., Nielsen, Per F., Huusfeldt, Per O., Johansen, Nils L., Madsen, Kjeld, Pedersen, Freddy Z., Thøgersen, Henning, Wilken, Michael, Agersø, Henrik·2000·Journal of Medicinal Chemistry

DOI 10.1021/jm9909645

Open this paper in CoChat — free account

Abstract

A series of very potent derivatives of the 30-amino acid peptide hormone glucagon-like peptide-1 (GLP-1) is described. The compounds were all derivatized with fatty acids in order to protract their action by facilitating binding to serum albumin. GLP-1 had a potency (EC(50)) of 55 pM for the cloned human GLP-1 receptor. Many of the compounds had similar or even higher potencies, despite quite large substituents. All compounds derivatized with fatty acids equal to or longer than 12 carbon atoms were very protracted compared to GLP-1 and thus seem suitable for once daily administration to type 2 diabetic patients. A structure-activity relationship was obtained. GLP-1 could be derivatized with linear fatty acids up to the length of 16 carbon atoms, sometimes longer, almost anywhere in the C-terminal part without considerable loss of potency. Derivatization with two fatty acid substituents led to a considerable loss of potency. A structure-activity relationship on derivatization of specific amino acids generally was obtained. It was found that the longer the fatty acid, the more potency was lost. Simultaneous modification of the N-terminus (in order to obtain better metabolic stability) interfered with fatty acid derivatization and led to loss of potency.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1021/jm9909645

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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
Nauck, M. A., Heimesaat, M. M., Orskov, C., Holst, J. J., Ebert, R., & Creutzfeldt, W. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116186 · Cited by 1,651
Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans.
Flint, A., Raben, A., Astrup, A., & Holst, J. J. (1998) · Journal of Clinical Investigation · doi:10.1172/jci990 · Cited by 1,402
Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV.
Kieffer, T. J., McIntosh, C. H., & Pederson, R. A. (1995) · Endocrinology · doi:10.1210/endo.136.8.7628397 · Cited by 1,124
Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in Type 2 (non-insulin-dependent) diabetic patients
Nauck, M. A., Kleine, N., �rskov, C., Holst, J. J., Willms, B., & Creutzfeldt, W. (1993) · Diabetologia · doi:10.1007/bf00401145 · Cited by 1,092
Truncated GLP-1 (proglucagon 78?107-amide) inhibits gastric and pancreatic functions in man
Wettergren, A., Schjoldager, B., Mortensen, P. E., Myhre, J., Christiansen, J., & Holst, J. J. (1993) · Digestive Diseases and Sciences · doi:10.1007/bf01316798 · Cited by 670
Exaggerated secretion of glucagon-like peptide-1 (GLP-1) could cause reactive hypoglycaemia
Toft-Nielsen, M., Madsbad, S., & Holst, J. J. (1998) · Diabetologia · doi:10.1007/s001250051049 · Cited by 132

Show all 6 references

The incretin system: Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes
Drucker, D. J., & Nauck, M. A. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69705-5 · Cited by 3,896
The Physiology of Glucagon-like Peptide 1
Holst, J. J. (2007) · Physiological Reviews · doi:10.1152/physrev.00034.2006 · Cited by 3,371
Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study
Armstrong, M. J., Gaunt, P., Aithal, G. P., Barton, D., Hull, D., Parker, R., Hazlehurst, J. M., Guo, K., Abouda, G., Aldersley, M. A., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(15)00803-x · Cited by 2,203
GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus
Meier, J. J. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.140 · Cited by 1,311
Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes
Nauck, M., Frid, A., Hermansen, K., Shah, N. S., Tankova, T., Mitha, I. H., Zdravkovic, M., Düring, M., Matthews, D. R., & for the LEAD-2 Study Group (2009) · Diabetes Care · doi:10.2337/dc08-1355 · Cited by 1,129
Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue semaglutide
Lau, J., Bloch, P., Schäffer, L., Pettersson, I., Spetzler, J., Kofoed, J., Madsen, K., Knudsen, L. B., McGuire, J., Steensgaard, D. B., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00726 · Cited by 1,105
Self-citation
Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial
Garber, A., Henry, R., Ratner, R., Garcia-Hernandez, P. A., Rodriguez-Pattzi, H., Olvera-Alvarez, I., Hale, P. M., Zdravkovic, M., & Bode, B. (2009) · The Lancet · doi:10.1016/s0140-6736(08)61246-5 · Cited by 1,057
The Discovery and Development of Liraglutide and Semaglutide
Knudsen, L. B., & Lau, J. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00155 · Cited by 970
Self-citation
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)
Zinman, B., Gerich, J., Buse, J. B., Lewin, A., Schwartz, S., Raskin, P., Hale, P. M., Zdravkovic, M., Blonde, L., & the LEAD-4 Study Investigators (2009) · Diabetes Care · doi:10.2337/dc08-2124 · Cited by 848
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
on behalf of the Liraglutide Effect and Action in Diabetes 5 (LEAD-5) met+SU Study Group, Russell-Jones, D., Vaag, A., Schmitz, O., Sethi, B. K., Lalic, N., Antic, S., Zdravkovic, M., Ravn, G. M., & Simó, R. (2009) · Diabetologia · doi:10.1007/s00125-009-1472-y · Cited by 835
The role of incretins in glucose homeostasis and diabetes treatment
Kim, W., & Egan, J. M. (2008) · Pharmacological Reviews · doi:10.1124/pr.108.000604 · Cited by 824
The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE−/− and LDLr−/− Mice by a Mechanism That Includes Inflammatory Pathways
Rakipovski, G., Rolin, B., Nøhr, J., Klewe, I., Frederiksen, K. S., Augustin, R., Hecksher-Sørensen, J., Ingvorsen, C., Polex-Wolf, J., & Knudsen, L. B. (2018) · JACC: Basic to Translational Science · doi:10.1016/j.jacbts.2018.09.004 · Cited by 509
Self-citation
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
Vilsbøll, T., Zdravkovic, M., Le-Thi, T., Krarup, T., Schmitz, O., Courrèges, J.-P., Verhoeven, R., Bugánová, I., & Madsbad, S. (2007) · Diabetes Care · doi:10.2337/dc06-2593 · Cited by 468
Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers
Edwards, C. M. B., Stanley, S. A., Davis, R., Brynes, A. E., Frost, G. S., Seal, L. J., Ghatei, M. A., & Bloom, S. R. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.281.1.e155 · Cited by 464
Glucagon-Like Peptide-1 and Its Class B G Protein–Coupled Receptors: A Long March to Therapeutic Successes
Graaf, C. D., Donnelly, D., Wootten, D., Lau, J., Sexton, P. M., Miller, L. J., Ahn, J.-M., Liao, J., Fletcher, M. M., Yang, D., et al. (2016) · Pharmacological Reviews · doi:10.1124/pr.115.011395 · Cited by 403
Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1)
Wysham, C., Blevins, T., Arakaki, R., Colon, G., Garcia, P., Atisso, C., Kuhstoss, D., & Lakshmanan, M. (2014) · Diabetes Care · doi:10.2337/dc13-2760 · Cited by 396
Prebiotic Peptides: Molecular Hubs in the Origin of Life
Frenkel-Pinter, M., Samanta, M., Ashkenasy, G., & Leman, L. J. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.9b00664 · Cited by 354
Chemistry and Biochemistry of Type 2 Diabetes
Ross, S. A., Gulve, E. A., & Wang, M. (2004) · Chemical Reviews · doi:10.1021/cr0204653 · Cited by 323
Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS
van Bloemendaal, L., ten Kulve, J. S., la Fleur, S. E., Ijzerman, R. G., & Diamant, M. (2014) · Journal of Endocrinology · doi:10.1530/joe-13-0414 · Cited by 312
Gastric emptying in diabetes: clinical significance and treatment
Horowitz, M., O’Donovan, D., Jones, K. L., Feinle, C., Rayner, C. K., & Samsom, M. (2002) · Diabetic Medicine · doi:10.1046/j.1464-5491.2002.00658.x · Cited by 308
Incretin-Based Therapies for Type 2 Diabetes Mellitus: Properties, Functions, and Clinical Implications
Nauck, M. A. (2011) · The American Journal of Medicine · doi:10.1016/j.amjmed.2010.11.002 · Cited by 295
Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of a Single-Dose of NN2211, a Long-Acting Glucagon-Like Peptide 1 Derivative, in Healthy Male Subjects
Elbrønd, B., Jakobsen, G., Larsen, S., Agersø, H., Jensen, L. B., Rolan, P., Sturis, J., Hatorp, V., & Zdravkovic, M. (2002) · Diabetes Care · doi:10.2337/diacare.25.8.1398 · Cited by 279
Self-citation
Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists
Liu, Q. K. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1431292 · Cited by 265
Bedtime Administration of NN2211, a Long-Acting GLP-1 Derivative, Substantially Reduces Fasting and Postprandial Glycemia in Type 2 Diabetes
Juhl, C. B., Hollingdal, M., Sturis, J., Jakobsen, G., Agersø, H., Veldhuis, J., Pørksen, N., & Schmitz, O. (2002) · Diabetes · doi:10.2337/diabetes.51.2.424 · Cited by 264
Self-citation
Systemic Administration of the Long-Acting GLP-1 Derivative NN2211 Induces Lasting and Reversible Weight Loss in Both Normal and Obese Rats
Larsen, P. J., Fledelius, C., Knudsen, L. B., & Tang-Christensen, M. (2001) · Diabetes · doi:10.2337/diabetes.50.11.2530 · Cited by 257
Self-citation
Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: Individual patient data meta-analysis of the LEAD program
Armstrong, M. J., Houlihan, D. D., Rowe, I. A., Clausen, W. H. O., Elbrønd, B., Gough, S. C. L., Tomlinson, J. W., & Newsome, P. N. (2013) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.12149 · Cited by 250
GLP−1 receptor agonists for the treatment of obesity: Role as a promising approach
Wang, J.-Y., Wang, Q.-W., Yang, X.-Y., Yang, W., Li, D.-R., Jin, J.-Y., Zhang, H.-C., & Zhang, X.-F. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1085799 · Cited by 248
Glucagon-like peptide analogues for type 2 diabetes mellitus
Shyangdan, D. S., Royle, P., Clar, C., Sharma, P., Waugh, N., & Snaith, A. (2011) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006423.pub2 · Cited by 246
Structure-activity and protraction relationship of long-acting glucagon-like peptide-1 derivatives: importance of fatty acid length, polarity, and bulkiness
Madsen, K., Knudsen, L. B., Agersoe, H., Nielsen, P. F., Thøgersen, H., Wilken, M., & Johansen, N. L. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm070861j · Cited by 244
Self-citation
Robust anti‐obesity and metabolic effects of a dual GLP ‐1/glucagon receptor peptide agonist in rodents and non‐human primates
Henderson, S. J., Konkar, A., Hornigold, D. C., Trevaskis, J. L., Jackson, R., Fritsch Fredin, M., Jansson‐Löfmark, R., Naylor, J., Rossi, A., Bednarek, M. A., et al. (2016) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12735 · Cited by 240
Efficacy and safety of liraglutide versus placebo as add-on to glucose-lowering therapy in patients with type 2 diabetes and moderate renal impairment (LIRA-RENAL): a randomized clinical trial
Davies, M. J., Bain, S. C., Atkin, S. L., Rossing, P., Scott, D., Shamkhalova, M. S., Bosch-Traberg, H., Syrén, A., & Umpierrez, G. E. (2016) · Diabetes Care · doi:10.2337/dc14-2883 · Cited by 235
“glucagon-like peptide 1 (GLP-1) analog (13), is completely metabolized through a proteolytic mechanism and is not predominantly eliminated by a single organ (14).”
Background
Small-molecule agonists for the glucagon-like peptide 1 receptor
Knudsen, L. B., Kiel, D., Teng, M., Behrens, C., Bhumralkar, D., Kodra, J. T., Holst, J. J., Jeppesen, C. B., Johnson, M. D., de Jong, J. C., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605701104 · Cited by 232
Self-citation
GLP-1 analog liraglutide protects against oxidative stress and albuminuria in streptozotocin-induced diabetic rats via protein kinase A-mediated inhibition of renal NAD(P)H oxidases
Hendarto, H., Inoguchi, T., Maeda, Y., Ikeda, N., Zheng, J., Takei, R., Yokomizo, H., Hirata, E., Sonoda, N., & Takayanagi, R. (2012) · Metabolism · doi:10.1016/j.metabol.2012.03.002 · Cited by 232
Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist
Kawai, T., Sun, B., Yoshino, H., Feng, D., Suzuki, Y., Fukazawa, M., Nagao, S., Wainscott, D. B., Showalter, A. D., Droz, B. A., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2014879117 · Cited by 231
Liraglutide in Type 2 Diabetes Mellitus: Clinical Pharmacokinetics and Pharmacodynamics
Jacobsen, L. V., Flint, A., Olsen, A. K., & Ingwersen, S. H. (2016) · Clinical Pharmacokinetics · doi:10.1007/s40262-015-0343-6 · Cited by 217
Impact of non-proteinogenic amino acids in the discovery and development of peptide therapeutics
Ding, Y., Ting, J. P., Liu, J., Al-Azzam, S., Pandya, P., & Afshar, S. (2020) · Amino Acids · doi:10.1007/s00726-020-02890-9 · Cited by 200
GLP-1 stimulates insulin secretion by PKC-dependent TRPM4 and TRPM5 activation
Shigeto, M., Ramracheya, R., Tarasov, A. I., Cha, C. Y., Chibalina, M. V., Hastoy, B., Philippaert, K., Reinbothe, T., Rorsman, N., Salehi, A., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci81975 · Cited by 189
Liraglutide
Drucker, D. J., Dritselis, A., & Kirkpatrick, P. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3148 · Cited by 181
Peptides As Therapeutics with Enhanced Bioactivity
Goodwin, D., Simerska, P., & Toth, I. (2012) · Current Medicinal Chemistry · doi:10.2174/092986712803251548 · Cited by 176
GLP-1/glucagon receptor co-agonism for treatment of obesity
Sánchez-Garrido, M. A., Brandt, S. J., Clemmensen, C., Müller, T. D., DiMarchi, R. D., & Tschöp, M. H. (2017) · Diabetologia · doi:10.1007/s00125-017-4354-8 · Cited by 175
Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes
Mahapatra, M. K., Karuppasamy, M., & Sahoo, B. M. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09699-1 · Cited by 166
Semaglutide as a promising antiobesity drug
Christou, G. A., Katsiki, N., Blundell, J., Fruhbeck, G., & Kiortsis, D. N. (2019) · Obesity Reviews · doi:10.1111/obr.12839 · Cited by 159
Regulation of Adipocyte Formation by GLP-1/GLP-1R Signaling
Challa, T. D., Beaton, N., Arnold, M., Rudofsky, G., Langhans, W., & Wolfrum, C. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.310342 · Cited by 149
Once-daily liraglutide versus lixisenatide as add-on to metformin in type 2 diabetes: a 26-week randomized controlled clinical trial
Nauck, M., Rizzo, M., Johnson, A., Bosch-Traberg, H., Madsen, J., & Cariou, B. (2016) · Diabetes Care · doi:10.2337/dc15-2479 · Cited by 143
Acylated heptapeptide binds albumin with high affinity and application as tag furnishes long-acting peptides
Zorzi, A., Middendorp, S. J., Wilbs, J., Deyle, K., & Heinis, C. (2017) · Nature Communications · doi:10.1038/ncomms16092 · Cited by 141
Incretin-based therapy: a powerful and promising weapon in the treatment of type 2 diabetes mellitus
Koliaki, C., & Doupis, J. (2011) · Diabetes Therapy · doi:10.1007/s13300-011-0002-3 · Cited by 140
Molecular, pharmacological and clinical aspects of liraglutide, a once-daily human GLP-1 analogue
Russell-Jones, D. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.11.018 · Cited by 137
GLP‐1 receptor agonists vs. DPP‐4 inhibitors for type 2 diabetes: is one approach more successful or preferable than the other?
Brunton, S. (2014) · International Journal of Clinical Practice · doi:10.1111/ijcp.12361 · Cited by 130
Administration of an acylated GLP-1 and GIP preparation provides added beneficial glucose-lowering and insulinotropic actions over single incretins in mice with Type 2 diabetes and obesity
Gault, V. A., Kerr, B. D., Harriott, P., & Flatt, P. R. (2011) · Clinical Science · doi:10.1042/cs20110006 · Cited by 125
The Human GLP-1 Analog Liraglutide and the Pancreas
Nyborg, N. C. B., Mølck, A.-M., Madsen, L. W., & Bjerre Knudsen, L. (2012) · Diabetes · doi:10.2337/db11-0936 · Cited by 125
Glucagon‐like peptide 1 receptor stimulation as a means of neuroprotection
Harkavyi, A., & Whitton, P. S. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00486.x · Cited by 125
The mechanism and efficacy of GLP-1 receptor agonists in the treatment of Alzheimer’s disease
Du, H., Meng, X., Yao, Y., & Xu, J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1033479 · Cited by 125
Incretins: their physiology and application in the treatment of diabetes mellitus
Tasyurek, H. M., Altunbas, H. A., Balci, M. K., & Sanlioglu, S. (2014) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2501 · Cited by 121
Comparative effects of the long-acting GLP-1 receptor ligands, liraglutide and exendin-4, on food intake and body weight suppression in rats
Hayes, M. R., Kanoski, S. E., Alhadeff, A. L., & Grill, H. J. (2011) · Obesity · doi:10.1038/oby.2011.50 · Cited by 110
Structurally Modified Analogues of Glucagon-Like Peptide-1 (GLP-1) and Glucose-Dependent Insulinotropic Polypeptide (GIP) As Future Antidiabetic Agents
Green, B., Gault, V., O'Harte, F., & Flatt, P. (2004) · Current Pharmaceutical Design · doi:10.2174/1381612043382774 · Cited by 111
GLP-1 receptor agonists: A clinical perspective on cardiovascular effects
Mundil, D., Cameron-Vendrig, A., & Husain, M. (2012) · Diabetes and Vascular Disease Research · doi:10.1177/1479164112441526 · Cited by 104
Exposure-response analyses of liraglutide 3.0 mg for weight management
Wilding, J. P. H., Overgaard, R. V., Jacobsen, L. V., Jensen, C. B., & le Roux, C. W. (2016) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12639 · Cited by 102
Design of Novel Exendin-Based Dual Glucagon-like Peptide 1 (GLP-1)/Glucagon Receptor Agonists
Evers, A., Haack, T., Lorenz, M., Bossart, M., Elvert, R., Henkel, B., Stengelin, S., Kurz, M., Glien, M., Dudda, A., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00174 · Cited by 101
Peptide lipidation stabilizes structure to enhance biological function
Ward, B. P., Ottaway, N. L., Perez-Tilve, D., Ma, D., Gelfanov, V. M., Tschöp, M. H., & DiMarchi, R. D. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.08.008 · Cited by 101
GLP1 Receptor Agonists—Effects beyond Obesity and Diabetes
Wilbon, S. S., & Kolonin, M. G. (2023) · Cells · doi:10.3390/cells13010065 · Cited by 101
Incretins in obesity and diabetes
Chia, C. W., & Egan, J. M. (2020) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14211 · Cited by 93
Role of glucagon-like peptide-1 in the pathogenesis and treatment of diabetes mellitus
León, D. D. D., Crutchlow, M. F., Ham, J.-Y. N., & Stoffers, D. A. (2006) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.07.011 · Cited by 94
Incretin Effects on β-Cell Function, Replication, and Mass
Garber, A. J. (2011) · Diabetes Care · doi:10.2337/dc11-s230 · Cited by 92
Liraglutide Improves Pancreatic Beta Cell Mass and Function in Alloxan-Induced Diabetic Mice
Tamura, K., Minami, K., Kudo, M., Iemoto, K., Takahashi, H., & Seino, S. (2015) · PLOS ONE · doi:10.1371/journal.pone.0126003 · Cited by 70
Novel GLP-1 receptor agonists for diabetes
Garber, A. J. (2012) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2012.638282 · Cited by 69
A Review on the Association between Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer
Chiu, W.-Y., Shih, S.-R., & Tseng, C.-H. (2012) · Experimental Diabetes Research · doi:10.1155/2012/924168 · Cited by 63
“Hindawi Publishing Corporation Experimental Diabetes Research Volume 2012, Article ID 924168, 7 pages doi:10.1155/2012/924168 Review Article”
BackgroundInfluential
Effects of liraglutide, a human glucagon-like peptide-1 analogue, on body weight, body fat area and body fat-related markers in patients with type 2 diabetes mellitus
Suzuki, D., Toyoda, M., Kimura, M., Miyauchi, M., Yamamoto, N., Sato, H., Tanaka, E., Kuriyama, Y., Miyatake, H., Abe, M., et al. (2013) · Internal Medicine · doi:10.2169/internalmedicine.52.8961 · Cited by 61
Lipopeptides for Vaccine Development
Hamley, I. W. (2021) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.1c00258 · Cited by 62
Efficacy and safety of long-acting glucagon-like peptide-1 receptor agonists compared with exenatide twice daily and sitagliptin in type 2 diabetes mellitus: A systematic review and meta-analysis
Pinelli, N. R., & Hurren, K. M. (2011) · Annals of Pharmacotherapy · doi:10.1345/aph.1q024 · Cited by 59
Designing a dual GLP-1R/GIPR agonist from tirzepatide: Comparing residues between tirzepatide, GLP-1, and GIP
Wang, L. (2022) · Drug Design, Development and Therapy · doi:10.2147/dddt.s358989 · Cited by 56
Liraglutide enhances glucose transporter 4 translocation via regulation of AMP-activated protein kinase signaling pathways in mouse skeletal muscle cells
Li, Z., Ni, C.-L., Yao, Z., Chen, L.-M., & Niu, W.-Y. (2014) · Metabolism · doi:10.1016/j.metabol.2014.05.008 · Cited by 56
Liraglutide 3.0 mg for weight management: weight-loss dependent and independent effects
Bays, H., Pi-Sunyer, X., Hemmingsson, J. U., Claudius, B., Jensen, C. B., & Van Gaal, L. (2017) · Current Medical Research and Opinion · doi:10.1080/03007995.2016.1251892 · Cited by 48
Liraglutide: clinical pharmacology and considerations for therapy
Sisson, E. M. (2011) · Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.31.9.896 · Cited by 49
Clinical Pharmacology of Incretin Therapies for Type 2 Diabetes Mellitus: Implications for Treatment
Neumiller, J. J. (2011) · Clinical Therapeutics · doi:10.1016/j.clinthera.2011.04.024 · Cited by 47
Anti-diabetic effects of GLP1 analogs are mediated by thermogenic interleukin-6 signaling in adipocytes
Gutierrez, A. D., Gao, Z., Hamidi, V., Zhu, L., Saint Andre, K. B., Riggs, K., Ruscheinsky, M., Wang, H., Yu, Y., Miller, C., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100813 · Cited by 44
“metronomic administration and sustained release in patients.(9,10) Incretin mimetics also have anti-obesity effects that are not completely understood.”
Background
Running on mixed fuel-dual agonistic approach of GLP-1 and GCG receptors leads to beneficial impact on body weight and blood glucose control: A comparative study between mice and non-human primates
Elvert, R., Herling, A. W., Bossart, M., Weiss, T., Zhang, B., Wenski, P., Wandschneider, J., Kleutsch, S., Butty, U., Kannt, A., et al. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13212 · Cited by 42
Treatment With Liraglutide-a Once-Daily GLP-1 Analog-Does Not Reduce the Bioavailability of Ethinyl Estradiol/Levonorgestrel Taken as an Oral Combination Contraceptive Drug
Jacobsen, L. V., Vouis, J., Hindsberger, C., & Zdravkovic, M. (2011) · The Journal of Clinical Pharmacology · doi:10.1177/0091270010389471 · Cited by 41
Is there a justification for classifying GLP-1 receptor agonists as basal and prandial?
Miñambres, I., & Pérez, A. (2017) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-017-0204-6 · Cited by 39
The Role of Basal Insulin and Glucagon-Like Peptide-1 Agonists in the Therapeutic Management of Type 2 Diabetes—A Comprehensive Review
Garg, S. K. (2010) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2009.0127 · Cited by 38
Glucagon-Like Peptide-1 Analog, Liraglutide, Delays Onset of Experimental Autoimmune Encephalitis in Lewis Rats
DellaValle, B., Brix, G. S., Brock, B., Gejl, M., Landau, A. M., Møller, A., Rungby, J., & Larsen, A. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00433 · Cited by 39
The effect of the once-daily human glucagon-like peptide 1 analog liraglutide on the pharmacokinetics of acetaminophen
Kapitza, C., Zdravkovic, M., Hindsberger, C., & Flint, A. (2011) · Advances in Therapy · doi:10.1007/s12325-011-0044-y · Cited by 36
GLP-1 receptor agonists, are we witnessing the emergence of a paradigm shift for neuro-cardio-metabolic disorders?
Arredouani, A. (2025) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2025.108824 · Cited by 36
Beyond Glucagon-like Peptide-1: Is G-Protein Coupled Receptor Polypharmacology the Path Forward to Treating Metabolic Diseases?
Sloop, K. W., Briere, D. A., Emmerson, P. J., & Willard, F. S. (2018) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.8b00009 · Cited by 31
Pharmacological profile, efficacy and safety of lixisenatide in type 2 diabetes mellitus
Forst, T., & Pfützner, A. (2013) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2013.838559 · Cited by 25
The risk of cardiovascular complications with current obesity drugs
Chao, A. M., Wadden, T. A., Berkowitz, R. I., Quigley, K., & Silvestry, F. (2020) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2020.1806234 · Cited by 23
Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Cardiac Disorders
Wroge, J., & Williams, N. T. (2016) · Annals of Pharmacotherapy · doi:10.1177/1060028016663218 · Cited by 17
Liraglutide in the treatment of type 2 diabetes mellitus: clinical utility and patient perspectives
Stephens, J., & Edavalath, M. (2010) · Patient Preference and Adherence · doi:10.2147/ppa.s6358 · Cited by 17
Impact of dose‐escalation schemes and drug discontinuation on weight loss outcomes with liraglutide 3.0 mg: A model‐based approach
Papathanasiou, T., Strathe, A., Agersø, H., Lund, T. M., & Overgaard, R. V. (2020) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13985 · Cited by 18
Self-citation

Authors: Knudsen, L. B., Nielsen, P. F., Huusfeldt, P. O., Johansen, N. L., Madsen, K., Pedersen, F. Z., Thøgersen, H., Wilken, M., & Agersø, H.
Venue: Journal of Medicinal Chemistry
Publisher: American Chemical Society (ACS)
Published: 2000-04-18
Volume: 43
Issue: 9
Pages: 1664-1669
ISSN: 0022-2623 (ISSN-L)
1520-4804
DOI: 10.1021/jm9909645
OpenAlex: W1986331352
Cited by: 700
References: 6
FWCI: 6.36
Type: journal article
Language: en
Open access: green

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.

Potent Derivatives of Glucagon-like Peptide-1 with Pharmacokinetic Properties Suitable for Once Daily Administration

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Self-check

Citations

Cites

Cited by

Metadata

Record

About these checks

Data sources