Comparison between insulin delivery methods: subcutaneous, inhaled, oral, and buccal
DOI:
https://doi.org/10.36105/psrua.2021v1n1.08Keywords:
diabetes, insulina, subcutánea, inhalada, oral, bucalAbstract
Diabetes mellitus is a complex and chronic metabolic disorder characterized by hyperglycemia. Part of the treatment for this condition is the administration of insulin, a protein that directly influences blood glucose levels. It is traditionally administered parenterally; however, new alternative ways for its application seek greater efficiency and less invasiveness. The objective of this article is to compare the different methods of insulin administration, taking into account new technologies. This review article provides an overview of diabetes and insulin, highlights the advantages and disadvantages of insulin delivery methods (subcutaneous, inhaled, oral, and buccal), and shows the new technologies that include biotechnological applications.
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1. Blair M. Diabetes Mellitus Review. Urol Nurs. 2016Jan-Feb;36(1):27-36.
2. Zaccardi F, Webb DR, Yates T, Davies MJ. Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective. Postgrad Med J. 2015;0:1-7. https://doi.org/10.1136/postgradmedj-2015-133281
3. World Health Organization. Classification of diabetes mellitus. 2019. License: CC BY-NC-SA 3.0 IGO.
4. American Diabetes Association. 2.Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes. 2020. Diabetes Care 2020;43(Suppl.1):S14–S31. https://doi.org/10.2337/dc20-s002
5. American Diabetes Association. 5.Facilitating behavior change and well-being to improve health outcomes: Standards of Medical Care in Diabetes. 2020. Diabetes Care 2020;43(Suppl.1):S48-S65. https://doi.org/10.2337/dc20-s005
6. American Diabetes Association. 9.Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes. 2020. Diabetes Care 2020;43(Suppl.1):S98–S110. https://doi.org/10.2337/dc20-s009
7. Drake MT, Smith SA. Optimizing Insulin Delivery in Patients with Diabetes Mellitus: Still Room for Improvement. Mayo Clin Proc. 2016Sep;91(9):1155-7. https://doi.org/10.1016/j.mayocp.2016.07.010
8. Frid AH, Hirsch LJ, Menchior AR, Morel DR, Strauss KW. Worldwide Injection Technique Questionnaire Study: Population Parameters and Injection Practices. Mayo Clin Proc. 2016Sep;91(9):1212-23. https://doi.org/10.1016/j.mayocp.2016.06.011
9. Frid AH, Hirsch LJ, Menchior AR, Morel DR, Strauss KW. Worldwide Injection Technique Questionnaire Study: Injecting Complications and the Role of the Professional. Mayo Clin Proc. 2016Sep;91(9):1224-30. https://doi.org/10.1016/j.mayocp.2016.06.012
10. Baumgard L. Insulin: pancreatic secretion and adipocyte regulation. Domest Anim Endocrinol. 2016;54:76-84. https://doi.org/10.1016/j.domaniend.2015.07.001
11. Freeland B, Farber MS. A Review of Insulin for the Treatment of Diabetes Mellitus. Home Healthc Now. 2016;34(8):416-23. https://doi.org/10.1097/NHH.0000000000000446
12. Cichocka E, Wietchy A, Nabrdalik K, Gumprecht J. Insulin therapy-new directions of research. Endokrynol Pol. 2016;67(3):314-24. https://doi.org/10.5603/EP.2016.0044
13. Ahmad K. Insulin sources and types: a review of insulin in terms of its mode on diabetes mellitus. J Tradit Chin Med. 2015;34(2):234-37. https://doi.org/10.1016/s0254-6272(14)60084-4
14. Schloot NC, Hood RC, Corrigan SM, Panek RL, Heise T. Concentrated insulins in current clinical practice. Diabetes Res Clin Pract. 2019Feb;148:93-101. https://doi.org/10.1016/j.diabres.2018.12.007
15. Cahn A, Miccoli R, Dardano A, Del Prato S. New forms of insulin and insulin therapies for the treatment of type 2 diabetes. Lancet: Diabetes Endocrinol. 2015;3(8):3-10. https://doi.org/10.1016/S2213-8587(15)00097-2
16. Wong C, Al-Salami H, Dass C. Microparticles, microcapsules and microspheres: A review of recent developments and prospects for oral delivery of insulin. Int J Pharm. 2018;537(1-2):223-44. https://doi.org/10.1016/j.ijpharm.2017.12.036
17. Kim E, Plosker G. AFREZZA® (insulin human) Inhalation Powder: A Review in Diabetes Mellitus. Drugs. 2015;75(14):1679-86. https://doi.org/10.1007/s40265-015-0472-0
18. Battelino T, Omladič J, Phillip M. Closed loop insulin delivery in diabetes. Best Pract Res Clin Endocrinol Metab. 2015;29(3):315-25. https://doi.org/10.1016/j.beem.2015.03.001
19. American Diabetes Association. Insulin administration. Diabetes Care. 2004Jan;27(suppl 1):s106-s109. https://doi.org/10.2337/diacare.27.2007.s106
20. Spollett G, Edelman SV, Mehner P, Walter C, Penfornis A. Improvement of Insulin Injection Technique: Examination of Current Issues and Recommendations. Diabetes Educ. 2016Aug;42(4):379-94. https://doi.org/10.1177/0145721716648017
21. Bailey TS, Stone JY. A novel pen-based Bluetooth-enabled insulin delivery system with insulin dose tracking and advice. Expert Opin Drug Deliv. 2017May;14(5):697-703. https://doi.org/10.1080/17425247.2017.1313831
22. Mitragotri S. Current status and future prospects of needle-free liquid jet injectors. Nat Rev Drug Discov. 2006;5:543–48. https://doi.org/https://doi.org/10.1038/nrd2076
23. Nimri R, Nir J, Phillip M. Insulin Pump Therapy. Am J Ther. 2020Jan/Feb;27(1):e30-e41. https://doi.org/10.1097/MJT.0000000000001097
24. Karges B. Association of Insulin Pump Therapy vs Insulin Injection Therapy with Severe Hypoglycemia, Ketoacidosis, and Glycemic Control Among Children, Adolescents, and Young Adults with Type 1 Diabetes. JAMA. 2017Oct10;318(14):1358-1366. https://doi.org/10.1001/jama.2017.13994
25. Newman SP. Drug delivery to the lungs: challenges and opportunities. Ther Deliv. 2017Jul;8(8):647-661. https://doi.org/10.4155/tde-2017-0037
26. Heinemann L, Parkin CG. Rethinking the Viability and Utility of Inhaled Insulin in Clinical Practice. J Diabetes Res. 2018Mar7;2018:4568903. https://doi.org/10.1155/2018/4568903
27. Easa N, Alany RG, Carew M, Vangala A. A review of non-invasive insulin delivery systems for diabetes therapy in clinical trials over the past decade. Drug Discov Today. 2019Feb;24(2):440-451. https://doi.org/10.1016/j.drudis.2018.11.010
28. Kim ES, Plosker GL. AFREZZA® (insulin human) Inhalation Powder: A Review in Diabetes Mellitus. Drugs. 2015Sep;75(14):1679-86. https://doi.org/10.1007/s40265-015-0472-0
29. Franzè S, Cilurzo F, Minghetti P. Insulin Biosimilars: The Impact on Rapid-Acting Analogue-Based Therapy. BioDrugs. 2015;29:113-21. https://doi.org/10.1007/s40259-015-0121-x
30. Shah RB, Patel M, Maahs DM, Shah VN. Insulin delivery methods: Past, present and future. Int J Pharm Investig. 2016Jan-Mar;6(1):1-9. https://doi.org/10.4103/2230-973X.176456
31. Hecq J, Siepmann F, Siepmann J, Amighi K, Goole J. Development and evaluation of chitosan and chitosan derivative nanoparticles containing insulin for oral administration. Drug Dev Ind Pharm. 2015;41(12):2037-44. https://doi.org/10.3109/03639045.2015.1044904
32. Ahsan SM, Thomas M, Reddy KK, Sooraparaju SG, Asthana A, Bhatnagar I. Chitosan as biomaterial in drug delivery and tissue engineering. Int J Biol Macromol. 2018Apr. https://doi.org/10.3390/molecules24101960
33. Sabu C, Raghav D, Jijith US, Mufeedha P, Naseef PP, Rathinasamy K, et al. Bioinspired oral insulin delivery system using yeast microcapsules. Mater Sci Eng C Mater Biol Appl. 2019Oct;103:109753. https://doi.org/10.1016/j.msec.2019.109753
34. Zhou X, Zhang X, Han S, Dou Y, Liu M, Zhang L, et al. Yeast Microcapsule-Mediated Targeted Delivery of Diverse Nanoparticles for Imaging and Therapy via the Oral Route. Nano Lett. 2017Feb8;17(2):1056-1064. https://doi.org/10.1016/j.omtn.2020.11.006
35. Lopes MA, Abrahim-Vieira B, Oliveira C, Fonte P, Souza AM, Lira T, et al. Probing insulin bioactivity in oral nanoparticles produced by ultrasonication-assisted emulsification/internal gelation. Int J Nanomedicine. 2015Sep18;10:5865-80. https://doi.org/10.2147/IJN.S86313
36. Zhang Y, Wei W, Lv P, Wang L, Ma G. Preparation and evaluation of alginate-chitosan microspheres for oral delivery of insulin. Eur J Pharm Biopharm. 2011Jan;77(1):11-9. https://doi.org/10.1016/j.ejpb.2010.09.016
37. Tong W, Song X, Gao C. Layer-by-layer assembly of microcapsules and their biomedical applications. Chem Soc Rev. 2012Sep21;41(18):6103-24. https://doi.org/10.1039/c2cs35088b
38. Silva BM, Borges AF, Silva C, Coelho JF, Simões S. Mucoadhesive oral films: The potential for unmet needs. Int J Pharm. 2015Oct15;494(1):537-51. https://doi.org/10.1016/j.ijpharm.2015.08.038
39. Lancina MG 3rd, Shankar RK, Yang H. Chitosan nanofibers for transbuccal insulin delivery. J Biomed Mater Res A. 2017 May;105(5):1252-1259. Erratum in: J Biomed Mater Res A. 2017Dec;105(12):3520. https://doi.org/10.1002/jbm.a.35984
40. Borges AF, Silva C, Coelho JF, Simões S. Oral films: Current status and future perspectives II - Intellectual property, technologies and market needs. J Control Release. 2015May28;206:108-21. https://doi.org/10.1016/j.jconrel.2015.03.012
41. Seyoum B, Abdulkadir J. Systematic inspection of insulin injection sites for local complications related to incorrect injection technique. Trop Doct. 1996Oct;26(4):159-61. https://doi.org/10.1177/004947559602600406
42. Barola A, Tiwari P, Bhansali A, Grover S, Dayal D. Insulin-Related Lipohypertrophy: Lipogenic Action or Tissue Trauma? Front Endocrinol (Lausanne). 2018;9:638. https://doi.org/10.3389/fendo.2018.00638
43. Kondo A, Nakamura A, Takeuchi J, Miyoshi H, Atsumi T. Insulin-Induced Distant Site Lipoatrophy. Diabetes Care. 2017Jun;40(6):e67-e68. https://doi.org/10.2337/dc16-2385
44. Lasalvia P, Barahona-Correa JE, Romero-Alvernia DM, Gil-Tamayo S, Castañeda-Cardona C, Bayona JG, et al. Pen Devices for Insulin Self-Administration Compared with Needle and Vial: Systematic Review of the Literature and Meta-Analysis. J Diabetes Sci Technol. 2016Jun28;10(4):959-66. https://doi.org/10.1177/1932296816633721
45. Ramadan WH, Khreis NA, Kabbara WK. Simplicity, safety, and acceptability of insulin pen use versus the conventional vial/syringe device in patients with type 1 and type 2 diabetes mellitus in Lebanon. Patient Prefer Adherence. 2015;9:517-28. https://doi.org/10.2147/PPA.S78225
46. Magwire ML. Addressing barriers to insulin therapy: the role of insulin pens. Am J Ther. 2011Sep;18(5):392-402. https://doi.org/10.1097/MJT.0b013e3181ef4dde
47. Engwerda EE, Tack CJ, de Galan BE. Needle-free jet injection of rapid-acting insulin improves early postprandial glucose control in patients with diabetes. Diabetes Care. 2013Nov;36(11):3436-41. https://doi.org/10.2337/dc13-0492
48. Kale TR, Momin M. Needle free injection technology-An overview. Innov Pharm. 2014;5:1–8. https://doi.org/10.4103/2230-973X.167662
49. Ravi AD, Sadhna D, Nagpaal D, Chawla L. Needle free injection technology: A complete insight. Int J Pharm Investig. 2015;5(4):192-199. https://doi.org/10.4103/2230-973X.167662
50. Conget-Donlo I, et al. [Cost-utility analysis of insulin pumps compared to multiple daily doses of insulin in patients with type 1 diabetes mellitus in Spain]. Rev. Esp. Salud Pública. 80:679–95. https://doi.org/10.1590/s1135-57272006000600008
51. Mbundu-Ilunga R, Camponovo C, Le Dizès O, Wojtusciszyn A. [Insulin pump treatment: For whom and how to set it up on an outpatient?]. Rev Med Suisse. 2020Jun;16(697):1191-1196.
52. Paldus B, Lee MH, O'Neal DN. Insulin pumps in general practice. Australian prescriber. 2018;41(6):186–190. https://doi.org/10.18773/austprescr.2018.056
53. Arbit E, Kidron M. Oral Insulin Delivery in a Physiologic Context: Review. J Diabetes Sci Technol. 2017Jul;11(4):825-832. https://doi.org/10.1177/1932296817691303
54. Rathbone M, Pather I, Şenel S. Overview of Oral Mucosal Delivery. Oral Mucosal Drug Delivery and Therapy. Advances in Delivery Science and Technology. Springer, Boston, MA. 2015.
2. Zaccardi F, Webb DR, Yates T, Davies MJ. Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective. Postgrad Med J. 2015;0:1-7. https://doi.org/10.1136/postgradmedj-2015-133281
3. World Health Organization. Classification of diabetes mellitus. 2019. License: CC BY-NC-SA 3.0 IGO.
4. American Diabetes Association. 2.Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes. 2020. Diabetes Care 2020;43(Suppl.1):S14–S31. https://doi.org/10.2337/dc20-s002
5. American Diabetes Association. 5.Facilitating behavior change and well-being to improve health outcomes: Standards of Medical Care in Diabetes. 2020. Diabetes Care 2020;43(Suppl.1):S48-S65. https://doi.org/10.2337/dc20-s005
6. American Diabetes Association. 9.Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes. 2020. Diabetes Care 2020;43(Suppl.1):S98–S110. https://doi.org/10.2337/dc20-s009
7. Drake MT, Smith SA. Optimizing Insulin Delivery in Patients with Diabetes Mellitus: Still Room for Improvement. Mayo Clin Proc. 2016Sep;91(9):1155-7. https://doi.org/10.1016/j.mayocp.2016.07.010
8. Frid AH, Hirsch LJ, Menchior AR, Morel DR, Strauss KW. Worldwide Injection Technique Questionnaire Study: Population Parameters and Injection Practices. Mayo Clin Proc. 2016Sep;91(9):1212-23. https://doi.org/10.1016/j.mayocp.2016.06.011
9. Frid AH, Hirsch LJ, Menchior AR, Morel DR, Strauss KW. Worldwide Injection Technique Questionnaire Study: Injecting Complications and the Role of the Professional. Mayo Clin Proc. 2016Sep;91(9):1224-30. https://doi.org/10.1016/j.mayocp.2016.06.012
10. Baumgard L. Insulin: pancreatic secretion and adipocyte regulation. Domest Anim Endocrinol. 2016;54:76-84. https://doi.org/10.1016/j.domaniend.2015.07.001
11. Freeland B, Farber MS. A Review of Insulin for the Treatment of Diabetes Mellitus. Home Healthc Now. 2016;34(8):416-23. https://doi.org/10.1097/NHH.0000000000000446
12. Cichocka E, Wietchy A, Nabrdalik K, Gumprecht J. Insulin therapy-new directions of research. Endokrynol Pol. 2016;67(3):314-24. https://doi.org/10.5603/EP.2016.0044
13. Ahmad K. Insulin sources and types: a review of insulin in terms of its mode on diabetes mellitus. J Tradit Chin Med. 2015;34(2):234-37. https://doi.org/10.1016/s0254-6272(14)60084-4
14. Schloot NC, Hood RC, Corrigan SM, Panek RL, Heise T. Concentrated insulins in current clinical practice. Diabetes Res Clin Pract. 2019Feb;148:93-101. https://doi.org/10.1016/j.diabres.2018.12.007
15. Cahn A, Miccoli R, Dardano A, Del Prato S. New forms of insulin and insulin therapies for the treatment of type 2 diabetes. Lancet: Diabetes Endocrinol. 2015;3(8):3-10. https://doi.org/10.1016/S2213-8587(15)00097-2
16. Wong C, Al-Salami H, Dass C. Microparticles, microcapsules and microspheres: A review of recent developments and prospects for oral delivery of insulin. Int J Pharm. 2018;537(1-2):223-44. https://doi.org/10.1016/j.ijpharm.2017.12.036
17. Kim E, Plosker G. AFREZZA® (insulin human) Inhalation Powder: A Review in Diabetes Mellitus. Drugs. 2015;75(14):1679-86. https://doi.org/10.1007/s40265-015-0472-0
18. Battelino T, Omladič J, Phillip M. Closed loop insulin delivery in diabetes. Best Pract Res Clin Endocrinol Metab. 2015;29(3):315-25. https://doi.org/10.1016/j.beem.2015.03.001
19. American Diabetes Association. Insulin administration. Diabetes Care. 2004Jan;27(suppl 1):s106-s109. https://doi.org/10.2337/diacare.27.2007.s106
20. Spollett G, Edelman SV, Mehner P, Walter C, Penfornis A. Improvement of Insulin Injection Technique: Examination of Current Issues and Recommendations. Diabetes Educ. 2016Aug;42(4):379-94. https://doi.org/10.1177/0145721716648017
21. Bailey TS, Stone JY. A novel pen-based Bluetooth-enabled insulin delivery system with insulin dose tracking and advice. Expert Opin Drug Deliv. 2017May;14(5):697-703. https://doi.org/10.1080/17425247.2017.1313831
22. Mitragotri S. Current status and future prospects of needle-free liquid jet injectors. Nat Rev Drug Discov. 2006;5:543–48. https://doi.org/https://doi.org/10.1038/nrd2076
23. Nimri R, Nir J, Phillip M. Insulin Pump Therapy. Am J Ther. 2020Jan/Feb;27(1):e30-e41. https://doi.org/10.1097/MJT.0000000000001097
24. Karges B. Association of Insulin Pump Therapy vs Insulin Injection Therapy with Severe Hypoglycemia, Ketoacidosis, and Glycemic Control Among Children, Adolescents, and Young Adults with Type 1 Diabetes. JAMA. 2017Oct10;318(14):1358-1366. https://doi.org/10.1001/jama.2017.13994
25. Newman SP. Drug delivery to the lungs: challenges and opportunities. Ther Deliv. 2017Jul;8(8):647-661. https://doi.org/10.4155/tde-2017-0037
26. Heinemann L, Parkin CG. Rethinking the Viability and Utility of Inhaled Insulin in Clinical Practice. J Diabetes Res. 2018Mar7;2018:4568903. https://doi.org/10.1155/2018/4568903
27. Easa N, Alany RG, Carew M, Vangala A. A review of non-invasive insulin delivery systems for diabetes therapy in clinical trials over the past decade. Drug Discov Today. 2019Feb;24(2):440-451. https://doi.org/10.1016/j.drudis.2018.11.010
28. Kim ES, Plosker GL. AFREZZA® (insulin human) Inhalation Powder: A Review in Diabetes Mellitus. Drugs. 2015Sep;75(14):1679-86. https://doi.org/10.1007/s40265-015-0472-0
29. Franzè S, Cilurzo F, Minghetti P. Insulin Biosimilars: The Impact on Rapid-Acting Analogue-Based Therapy. BioDrugs. 2015;29:113-21. https://doi.org/10.1007/s40259-015-0121-x
30. Shah RB, Patel M, Maahs DM, Shah VN. Insulin delivery methods: Past, present and future. Int J Pharm Investig. 2016Jan-Mar;6(1):1-9. https://doi.org/10.4103/2230-973X.176456
31. Hecq J, Siepmann F, Siepmann J, Amighi K, Goole J. Development and evaluation of chitosan and chitosan derivative nanoparticles containing insulin for oral administration. Drug Dev Ind Pharm. 2015;41(12):2037-44. https://doi.org/10.3109/03639045.2015.1044904
32. Ahsan SM, Thomas M, Reddy KK, Sooraparaju SG, Asthana A, Bhatnagar I. Chitosan as biomaterial in drug delivery and tissue engineering. Int J Biol Macromol. 2018Apr. https://doi.org/10.3390/molecules24101960
33. Sabu C, Raghav D, Jijith US, Mufeedha P, Naseef PP, Rathinasamy K, et al. Bioinspired oral insulin delivery system using yeast microcapsules. Mater Sci Eng C Mater Biol Appl. 2019Oct;103:109753. https://doi.org/10.1016/j.msec.2019.109753
34. Zhou X, Zhang X, Han S, Dou Y, Liu M, Zhang L, et al. Yeast Microcapsule-Mediated Targeted Delivery of Diverse Nanoparticles for Imaging and Therapy via the Oral Route. Nano Lett. 2017Feb8;17(2):1056-1064. https://doi.org/10.1016/j.omtn.2020.11.006
35. Lopes MA, Abrahim-Vieira B, Oliveira C, Fonte P, Souza AM, Lira T, et al. Probing insulin bioactivity in oral nanoparticles produced by ultrasonication-assisted emulsification/internal gelation. Int J Nanomedicine. 2015Sep18;10:5865-80. https://doi.org/10.2147/IJN.S86313
36. Zhang Y, Wei W, Lv P, Wang L, Ma G. Preparation and evaluation of alginate-chitosan microspheres for oral delivery of insulin. Eur J Pharm Biopharm. 2011Jan;77(1):11-9. https://doi.org/10.1016/j.ejpb.2010.09.016
37. Tong W, Song X, Gao C. Layer-by-layer assembly of microcapsules and their biomedical applications. Chem Soc Rev. 2012Sep21;41(18):6103-24. https://doi.org/10.1039/c2cs35088b
38. Silva BM, Borges AF, Silva C, Coelho JF, Simões S. Mucoadhesive oral films: The potential for unmet needs. Int J Pharm. 2015Oct15;494(1):537-51. https://doi.org/10.1016/j.ijpharm.2015.08.038
39. Lancina MG 3rd, Shankar RK, Yang H. Chitosan nanofibers for transbuccal insulin delivery. J Biomed Mater Res A. 2017 May;105(5):1252-1259. Erratum in: J Biomed Mater Res A. 2017Dec;105(12):3520. https://doi.org/10.1002/jbm.a.35984
40. Borges AF, Silva C, Coelho JF, Simões S. Oral films: Current status and future perspectives II - Intellectual property, technologies and market needs. J Control Release. 2015May28;206:108-21. https://doi.org/10.1016/j.jconrel.2015.03.012
41. Seyoum B, Abdulkadir J. Systematic inspection of insulin injection sites for local complications related to incorrect injection technique. Trop Doct. 1996Oct;26(4):159-61. https://doi.org/10.1177/004947559602600406
42. Barola A, Tiwari P, Bhansali A, Grover S, Dayal D. Insulin-Related Lipohypertrophy: Lipogenic Action or Tissue Trauma? Front Endocrinol (Lausanne). 2018;9:638. https://doi.org/10.3389/fendo.2018.00638
43. Kondo A, Nakamura A, Takeuchi J, Miyoshi H, Atsumi T. Insulin-Induced Distant Site Lipoatrophy. Diabetes Care. 2017Jun;40(6):e67-e68. https://doi.org/10.2337/dc16-2385
44. Lasalvia P, Barahona-Correa JE, Romero-Alvernia DM, Gil-Tamayo S, Castañeda-Cardona C, Bayona JG, et al. Pen Devices for Insulin Self-Administration Compared with Needle and Vial: Systematic Review of the Literature and Meta-Analysis. J Diabetes Sci Technol. 2016Jun28;10(4):959-66. https://doi.org/10.1177/1932296816633721
45. Ramadan WH, Khreis NA, Kabbara WK. Simplicity, safety, and acceptability of insulin pen use versus the conventional vial/syringe device in patients with type 1 and type 2 diabetes mellitus in Lebanon. Patient Prefer Adherence. 2015;9:517-28. https://doi.org/10.2147/PPA.S78225
46. Magwire ML. Addressing barriers to insulin therapy: the role of insulin pens. Am J Ther. 2011Sep;18(5):392-402. https://doi.org/10.1097/MJT.0b013e3181ef4dde
47. Engwerda EE, Tack CJ, de Galan BE. Needle-free jet injection of rapid-acting insulin improves early postprandial glucose control in patients with diabetes. Diabetes Care. 2013Nov;36(11):3436-41. https://doi.org/10.2337/dc13-0492
48. Kale TR, Momin M. Needle free injection technology-An overview. Innov Pharm. 2014;5:1–8. https://doi.org/10.4103/2230-973X.167662
49. Ravi AD, Sadhna D, Nagpaal D, Chawla L. Needle free injection technology: A complete insight. Int J Pharm Investig. 2015;5(4):192-199. https://doi.org/10.4103/2230-973X.167662
50. Conget-Donlo I, et al. [Cost-utility analysis of insulin pumps compared to multiple daily doses of insulin in patients with type 1 diabetes mellitus in Spain]. Rev. Esp. Salud Pública. 80:679–95. https://doi.org/10.1590/s1135-57272006000600008
51. Mbundu-Ilunga R, Camponovo C, Le Dizès O, Wojtusciszyn A. [Insulin pump treatment: For whom and how to set it up on an outpatient?]. Rev Med Suisse. 2020Jun;16(697):1191-1196.
52. Paldus B, Lee MH, O'Neal DN. Insulin pumps in general practice. Australian prescriber. 2018;41(6):186–190. https://doi.org/10.18773/austprescr.2018.056
53. Arbit E, Kidron M. Oral Insulin Delivery in a Physiologic Context: Review. J Diabetes Sci Technol. 2017Jul;11(4):825-832. https://doi.org/10.1177/1932296817691303
54. Rathbone M, Pather I, Şenel S. Overview of Oral Mucosal Delivery. Oral Mucosal Drug Delivery and Therapy. Advances in Delivery Science and Technology. Springer, Boston, MA. 2015.
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2021-07-22
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Alejandro Juárez, B., Fleischmann-de la Parra, P., Rayo-Mercado, K. T. E., & Ponce-Lopez, T. (2021). Comparison between insulin delivery methods: subcutaneous, inhaled, oral, and buccal. Proceedings of Scientific Research Universidad Anáhuac. Multidisciplinary Journal of Healthcare, 1(1), 62–71. https://doi.org/10.36105/psrua.2021v1n1.08
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