Lu X, et al. Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy. Dec 01. 2024. https://doi.org/10.1038/s41392-024-01951-9
Plows SJBPRCVMH. JF, The pathophysiology of gestational diabetes mellitus. Int J Mol Sci, 2018.
Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Publishing Group. 2018. https://doi.org/10.1038/nrendo.2017.151
Cho NH, et al. IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. Apr. 2018;138:271–81. https://doi.org/10.1016/j.diabres.2018.02.023
Classification and diagnosis of diabetes. Standards of medical care in Diabetes-2020. Diabetes Care. Jan. 2020;43:S14–31. https://doi.org/10.2337/dc20-S002
Powers MA et al. Jul., Diabetes Self-management Education and Support in Adults with Type 2 Diabetes: A Consensus Report of the American Diabetes Association, the Association of Diabetes Care & Education Specialists, the Academy of Nutrition and Dietetics, the American Academy of Family Physicians, the American Academy of PAs, the American Association of Nurse Practitioners, and the American Pharmacists Association, Diabetes Care, vol. 43, no. 7, pp. 1636–1649, 2020, https://doi.org/10.2337/dci20-0023
Goyal SMJI. R, Type 2 diabetes. StatPearls Publishing; 2025.
L.-S. A. S. B-VAJS H. U. K. O. H. M. C., Galicia-Garcia U. Pathophysiology of Type 2 Diabetes Mellitus., Int J Mol Sci, 2020.
Federation ID. IDF Diabetes Atlas, 10th edn., Brussels, Belgium: 2021. Available at: https://www.diabetesatlas.org
Minal DATASMH, Patel R. Economic burden, financial stress, and cost-related coping among people with uncontrolled diabetes in the U.S. Prev Med Rep, 34, 2023.
Ganesan RMSS. K, Oral Hypoglycemic Medications. 2025.
Feingold KR, et al. editors. Oral and injectable (Non-Insulin) Pharmacological agents for the treatment of type 2 diabetes., South Dartmouth (MA): MDText.com, Inc.
Davies MJ et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American diabetes association (ADA) and the European association for the study of diabetes (EASD), dec. 01, 2018. Am Diabetes Association Inc https://doi.org/10.2337/dci18-0033
DeFronzo RA, et al. Type 2 diabetes mellitus. Nat Rev Dis Primers. Jul. 2015;1. https://doi.org/10.1038/nrdp.2015.19
Chaudhury A, et al. Clinical review of antidiabetic drugs: implications for type 2 diabetes mellitus management. Front Endocrinol (Lausanne). Jan. 2017;8. https://doi.org/10.3389/fendo.2017.00006
Cerillo PM. JL, Liraglutide. StatPearls Publishing; 2024.
Knudsen LB, Lau J. The discovery and development of liraglutide and semaglutide. Front Media S A. 2019. https://doi.org/10.3389/fendo.2019.00155
Zheng Z, et al. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Signal Transduct Target Ther. Sep. 2024;9(1):234. https://doi.org/10.1038/s41392-024-01931-z
Tamayo-Trujillo R, et al. Molecular mechanisms of semaglutide and liraglutide as a therapeutic option for obesity. Front Media SA. 2024. https://doi.org/10.3389/fnut.2024.1398059
Knudsen NPHP. LB, Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration., J Med Chem., 2000.
Mahapatra KMSBM. MK, Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes. Rev Endocr Metab Disord, 2022.
The Business Research Company. Liraglutide Market Report 2024.
Roots analysis. -Business research and consulting, GLP-1 Market.
Food US, Administration D. FDA approves first generic of Once-Daily GLP-1 injection to lower blood sugar in patients with type 2 diabetes.
Anil ARBSSDRDB, Jindal B. Long-acting parenteral drug delivery systems for the treatment of chronic diseases. Adv Drug Deliv Rev, 198, 2023.
Gupta V. Glucagon-like peptide-1 analogues: an overview. Indian J Endocrinol Metab, 2013.
Collins CR. L, Glucagon-Like Peptide-1 receptor agonists, StatPearls Publishing LLC.
Drucker DJ. Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1, Apr. 03, 2018, Cell Press. https://doi.org/10.1016/j.cmet.2018.03.001
0rskov C, Holst JJ, Nielsen V. Effect of truncated Glucagon-Like Peptide-1 [Proglucagon-(78–107) amide] on endocrine secretion from pig pancreas, antrum, and nonantral stomach, 2009.
Vilsbøll T, Agersø H, Krarup T, Holst JJ. Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. J Clin Endocrinol Metab. Jan. 2003;88(1):220–4. https://doi.org/10.1210/jc.2002-021053
K. HBKL, Adelhorst O. K, Structure-activity studies of glucagon-like peptide-1. J Biol Chem, 1994.
Donnelly D. The structure and function of the glucagon-like peptide-1 receptor and its ligands. Br J Pharmacol, 2012.
Jacobsen LV, Flint A, Olsen AK, Ingwersen SH. Liraglutide in type 2 diabetes mellitus: clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. Jun. 2016;55(6):657–72. https://doi.org/10.1007/s40262-015-0343-6
Malm-Erjefält M et al. Nov., 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 Metabolism and Disposition, vol. 38, no. 11, pp. 1944–1953, 2010, https://doi.org/10.1124/dmd.110.034066
Roques BP, Noble F, Daugé V, Fournié-Zaluski MC, Beaumont A. Neutral endopeptidase 24.11: structure, inhibition, and experimental and clinical Pharmacology. Pharmacol Rev. 1993;1:87–146.
Plamboeck A, et al. The effect of exogenous GLP-1 on food intake is lost in male truncally vagotomized subjects with pyloroplasty. Am J Physiol Gastrointest Liver Physiol. 2013;304:1117–27. https://doi.org/10.1152/ajpgi.00035.2013.-Rapid
Hermansen K, et al. Liraglutide suppresses postprandial triglyceride and Apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled, cross-over trial. Diabetes Obes Metab. 2013;15(11):1040–8. https://doi.org/10.1111/dom.12133
Article CAS PubMed Google Scholar
Elbrønd B 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, 2002.
Agersù H, Jensen LB, Elbrùnd B, Rolan P, Zdravkovic M. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men, 2002.
Badgujar D, Bawake S, Sharma N. A comprehensive study on the identification and characterization of major degradation products of synthetic liraglutide using liquid chromatography-high resolution mass spectrometry, Journal of Peptide Science, Jan. 2024, https://doi.org/10.1002/psc.3652
Latif W, Lambrinos KJ, Patel P, StatPearls et al. StatPearls Publishing, 2025.
Htike ZZ, Zaccardi F, Papamargaritis D, Webb DR, Khunti K, Davies MJ. Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis. Diabetes Obes Metab. Apr. 2017;19(4):524–36. https://doi.org/10.1111/dom.12849
Dungan KM et al. Oct., Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): A randomised, open-label, phase 3, non-inferiority trial, The Lancet, vol. 384, no. 9951, pp. 1349–1357, 2014, https://doi.org/10.1016/S0140-6736(14)60976-4
Hu EH, Tsai ML, Lin Y, Chou TS, Chen TH. A review and Meta-Analysis of the safety and efficacy of using Glucagon-like Peptide-1 receptor agonists. Mar 01 2024 Multidisciplinary Digit Publishing Inst (MDPI). https://doi.org/10.3390/medicina60030357
I. K. KS, Liu YD. Y, Cardioprotective effects of GLP-1(28-36a): A degraded metabolite or GLP-1’s better half? J Diabetes Investig, 2020.
Krammer T et al. Mar., Cardioprotective effects of semaglutide on isolated human ventricular myocardium., Eur J Heart Fail, 2025, https://doi.org/10.1002/ejhf.3644
Xie S, et al. Long-Term activation of Glucagon-like peptide-1 receptor by dulaglutide prevents diabetic heart failure and metabolic remodeling in type 2 diabetes. J Am Heart Assoc. Oct. 2022;11(19). https://doi.org/10.1161/JAHA.122.026728
A BSTRACT. [Online]. Available: http://www.aapsj.org
Zapadka KL, et al. A pH-Induced switch in human Glucagon-like Peptide-1 aggregation kinetics. J Am Chem Soc. Dec. 2016;138(50):16259–65. https://doi.org/10.1021/jacs.6b05025
Jha NN, Anoop A, Ranganathan S, Mohite GM, Padinhateeri R, Maji SK. Characterization of amyloid formation by glucagon-like peptides: Role of basic residues in heparin-mediated aggregation, Biochemistry, vol. 52, no. 49, pp. 8800–8810, Dec. 2013, https://doi.org/10.1021/bi401398k
Poon S, Birkett NR, Fowler SB, Luisi BF, Dobson CM, Zurdo J. Amyloidogenicity and aggregate cytotoxicity of human Glucagon-Like Peptide-1 (hGLP-1), 2009.
Bothe JR, Andrews A, Smith KJ, Joyce LA, Krishnamachari Y, Kashi S. Peptide oligomerization memory effects and their impact on the physical stability of the GLP-1 agonist liraglutide. Mol Pharm. May 2019;16(5):2153–61. https://doi.org/10.1021/acs.molpharmaceut.9b00106
Nielsen L, et al. Effect of environmental factors on the kinetics of insulin fibril formation: Elucidation of the molecular mechanism. Biochemistry. May 2001;40:6036–46. https://doi.org/10.1021/bi002555c
Wang Y, Lomakin A, Kanai S, Alex R, Benedek GB. Transformation of oligomers of lipidated peptide induced by change in pH, Mol Pharm, vol. 12, no. 2, pp. 411–419, Feb. 2015, https://doi.org/10.1021/mp500519s
Frederiksen TM, et al. Oligomerization of a Glucagon-like peptide 1 analog: bridging experiment and simulations. Biophys J. Sep. 2015;109(6):1202–13. https://doi.org/10.1016/j.bpj.2015.07.051
ferrone1999.
Buckley ST et al. Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist,., 2018. [Online]. Available: http://stm.sciencemag.org/
Drucker DJ. Advances in oral peptide therapeutics. Apr 01 2020 Nature Research. https://doi.org/10.1038/s41573-019-0053-0
Shi Y et al. Feb., Oral delivery of liraglutide-loaded Poly-N-(2-hydroxypropyl) methacrylamide/chitosan nanoparticles: Preparation, characterization, and pharmacokinetics, J Biomater Appl, vol. 35, no. 7, pp. 754–761, 2021, https://doi.org/10.1177/0885328220947889
Tsai LC, Chen CH, Lin CW, Ho YC, Mi FL. Development of mutlifunctional nanoparticles self-assembled from trimethyl chitosan and fucoidan for enhanced oral delivery of insulin, Int J Biol Macromol, vol. 126, pp. 141–150, Apr. 2019, https://doi.org/10.1016/j.ijbiomac.2018.12.182
Chen Y, et al. Controlled release of liraglutide using thermogelling polymers in treatment of diabetes. Sci Rep. Aug. 2016;6. https://doi.org/10.1038/srep31593
Chavoshi F, Mirjalili SZ, Mohammadi A, Amini M, Somsen GW, Shirangi M. Forced degradation products of liraglutide: A comparative study of similarity between originator and analogue version by liquid Chromatography–Mass spectrometry. Int J Pept Res Ther. May 2024;30(3). https://doi.org/10.1007/s10989-024-10608-8
Fincke A, Winter J, Bunte T, Olbrich C. Thermally induced degradation pathways of three different antibody-based drug development candidates. Eur J Pharm Sci. Oct. 2014;62:148–60. https://doi.org/10.1016/j.ejps.2014.05.014
Nordisk N, Leginus IJ. CHEMISTRY REVIEW NDA 206321 SaxendaTM (Liraglutide [rDNA origin] Injection) For the Division of Metabolism and Endocrinology Products CHEMISTRY REVIEW #1.
D. VJBVJSK G. T. S. N. B. D. S. RP., Sheikh AR. Reactivity of N terminal histidine of peptides towards excipients/impurity of excipients: A case study of liraglutide excipient compatibility study., J Pharm Sci., 2024.
Nugrahadi HWFHSCAC. PP, Designing formulation strategies for enhanced stability of therapeutic peptides in aqueous solutions: A review. Pharmaceutics, 2023.
Ajit JMD et al. Reaction of a peptide with Polyvinylpyrrolidone in the solid state, 2003.
Li R, D’Souza AJ, Schowen RL, Borchardt RT, Topp EM, Laird BB. Effects of solution Polarity and viscosity on peptide deamidation. J Pept Res. 2000;56(5):326–34. https://doi.org/10.1034/j.1399-3011.2000.00783.x
Article CAS PubMed Google Scholar
parkins2000.
van de Hovgaard WM. Pharmaceutical Formulation Development of Peptides and Proteins, 1st Edition. 2000.
Drucker DJ, Dritselis A, Kirkpatrick P. Liraglutide, Apr. 2010. https://doi.org/10.1038/nrd3148
Elsayed KTID. YY, Regulatory guidelines for the analysis of therapeutic peptides and proteins. J Pept Sci, 2025.
Chou DK, Krishnamurthy R, Randolph TW, Carpenter JF, Manning MC. Effects of tween 20® and tween 80® on the stability of Albutropin during agitation. J Pharm Sci. 2005;94(6):1368–81. https://doi.org/10.1002/jps.20365
Article CAS PubMed Google Scholar
Lahlou A, Blanchet B, Carvalho M, Paul M, Astier A. Mechanically-induced aggregation of the monoclonal antibody cetuximab. Ann Pharm Fr. Sep. 2009;67(5):340–52. https://doi.org/10.1016/j.pharma.2009.05.008
Lentzen G, Schwarz T. Extremolytes: natural compounds from extremophiles for versatile applications. Oct. 2006. https://doi.org/10.1007/s00253-006-0553-9
Panuszko A, Bruździak P, Kaczkowska E, Stangret J. General mechanism of osmolytes’ influence on Protein Stability Irrespective of the Type of Osmolyte Cosolvent.
Galinski EA, Stein M, Amendt B, Kinder M. The Kosmotropic (Structure-Forming) Effect of Compensatory Solutes, 1997.
Avanti C, Saluja V, Van Streun ELP, Frijlink HW, Hinrichs WLJ. Stability of lysozyme in aqueous extremolyte solutions during heat shock and accelerated thermal conditions. PLoS ONE. Jan. 2014;9(1). https://doi.org/10.1371/journal.pone.0086244
Bolen DW, Rose GD. Structure and energetics of the hydrogen-bonded backbone in protein folding, 2008. https://doi.org/10.1146/annurev.biochem.77.061306.131357
Pandey A, Rath G, Chawala R, Goyal AK. A comprehensive review on liraglutide and novel nanocarrier-based systems for the effective delivery of liraglutide. Springer Sci Bus Media Deutschland GmbH. 2025. https://doi.org/10.1007/s00210-025-03918-1
Ayhan TÖTSBT. I, Injection site reaction induced by liraglutide use in a female patient with obesity. JCEM Case Rep, 2023.
U. I. AW, Q. OMOSSZA, Din FU. Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. Int J Nanomed, 2017.
Din FU et al. Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. Oct 05 2017 Dove Med Press Ltd https://doi.org/10.2147/IJN.S146315
Mishra B, Patel BB, Tiwari S. Colloidal nanocarriers: a review on formulation technology, types and applications toward targeted drug delivery. Elsevier Inc. 2010. https://doi.org/10.1016/j.nano.2009.04.008
How CW, Rasedee A, Manickam S, Rosli R. Tamoxifen-loaded nanostructured lipid carrier as a drug delivery system: Characterization, stability assessment and cytotoxicity, Colloids Surf B Biointerfaces, vol. 112, pp. 393–399, Dec. 2013, https://doi.org/10.1016/j.colsurfb.2013.08.009
Jakhar DK, et al. Fat fighting liraglutide based nano-formulation to reverse obesity: design, development and animal trials. Int J Pharm. Mar. 2023;634. https://doi.org/10.1016/j.ijpharm.2023.122585
Luo YCFYM. XM, Nanomedicine for the treatment of diabetes-associated cardiovascular diseases and fibrosis. Adv Drug Deliv Rev, 2021.
Murat Yanat KS. Preparation methods and applications of Chitosan nanoparticles; with an outlook toward reinforcement of biodegradable packaging. React Funct Polym, 161, 2021.
van der Jerome E, Paques P. Preparation methods of alginate nanoparticles. Adv Colloid Interface Sci, 209, 2014.
Madkhali OA. Drug delivery of gelatin nanoparticles as a biodegradable polymer for the treatment of infectious diseases: perspectives and challenges. Polym (Basel), 2023.
R. J. U. W. E. P. N. V. O. B. K. W. P. JH. Rao NV, hyaluronic acid nanoparticles as nanomedicine for treatment of inflammatory diseases. Pharmaceutics, 2020.
K. A. A. N-K. Y. M. M. M. Z. N. Z. V. R. A. A. S. H. Y. J. SW. Sadat Tabatabaei Mirakabad F, PLGA-based nanoparticles as cancer drug delivery systems. Asian Pac J Cancer Prev., 2014.
D.-W. MABEFE, Łukasiewicz M. S, Polycaprolactone nanoparticles as promising candidates for nanocarriers in novel nanomedicines. Pharmaceutics, 2021.
F. S. N. A. C. S. N. M. F. de L. M. M. F. C. I. S. S.-M. N. André de Almeida Campos L, Zein nanoparticles for drug delivery: Preparation methods and biological applications. Int J Pharm, 2023.
A. SSAGR, Iqbal HMAMAZ. O, Moxifloxacin loaded nanoparticles of disulfide bridged thiolated chitosan-eudragit RS100 for controlled drug delivery. Int J Biol Macromol, 2021.
McConnell SMAWBEL. An investigation into the digestion of Chitosan (noncrosslinked and crosslinked) by human colonic bacteria. J Pharm Sci, 2008.
X. W. D. X. LHZJLCS, Yuan Y. Y, Fabrication and characterization of Zein nanoparticles by dextran sulfate coating as vehicles for delivery of Curcumin. Int J Biol Macromol, 2020.
Ziebarth J, et al. Oral delivery of Liraglutide-Loaded Zein/Eudragit-Chitosan nanoparticles provides Pharmacokinetic and glycemic outcomes comparable to its subcutaneous injection in rats. Pharmaceutics. May 2024;16(5). https://doi.org/10.3390/pharmaceutics16050634
Ismail R, Bocsik A, Katona G, Gróf I, Deli MA, Csóka I. Encapsulation in polymeric nanoparticles enhances the enzymatic stability and the permeability of the glp-1 analog, liraglutide, across a culture model of intestinal permeability. Pharmaceutics. Nov. 2019;11(11). https://doi.org/10.3390/pharmaceutics11110599
Yedi Herdiana NWSSMM. Scale-up polymeric-based nanoparticles drug delivery systems: development and challenges. OpenNano, 7, 2022.
Thapa KJO. RK, Nanomedicine-based commercial formulations: current developments and future prospects. J Pharm Investig, 2023.
Jha SK et al. Dec., Enhanced antitumor efficacy of bile acid-lipid complex-anchored docetaxel nanoemulsion via oral metronomic scheduling, Journal of Controlled Release, vol. 328, pp. 368–394, 2020, https://doi.org/10.1016/j.jconrel.2020.08.067
Kweon S, et al. Coordinated ASBT and EGFR mechanisms for optimized liraglutide nanoformulation absorption in the GI tract. Int J Nanomed. 2024;19:2973–92. https://doi.org/10.2147/IJN.S442617
Bose A, Burman DR, Sikdar B, Patra P. Nanomicelles: Types, properties and applications in drug delivery, Feb. 01, 2021, John Wiley and Sons Inc. https://doi.org/10.1049/nbt2.12018
Subedi BAPSSJCSS. L, An oral liraglutide nanomicelle formulation conferring reduced insulin-resistance and long-term hypoglycemic and lipid metabolic benefits., J Control Release., 2025.
Sharma V, Das Mukhopadhyay C. Exosome as drug delivery system: current advancements. Extracell Vesicle. Jun. 2024;3:100032. https://doi.org/10.1016/j.vesic.2023.100032
Comments (0)