Published: 2017-01-28

Insulin delivery: what is new in the queue?

Syed Kasfur Rahman, Pallavi Kawatra


Diabetes Mellitus (DM) is a cluster of  metabolic disorders with the shared feature of hyperglycemia which may be due to discrete etiopathogenesis. India stands to be the diabetic capital of the world, second only to China. After its discovery by Banting and Best, it has been established that insulin plays a fundamental role in the management of DM. In spite of insulin being in the market for so long, what still remains a challenge is the invasive approach of its administration. Conventional pharmacotherapeutic approaches of insulin delivery that have been available over the years are insulin syringes, pumps and pens. Upcoming innovative modes of insulin delivery include oral insulin, inhaled insulin, colonic insulin delivery, transdermal insulin, intra-peritoneal insulin, intra-nasal insulin, nano-technology etc. Constant research has been going on since many years to discover a route of administration for insulin that is minimally or noninvasive, effective, safe, convenient and cost-effective for patients. If successful, alternative routes of administration could revolutionize the treatment of DM and help improve patients’ quality of life.


Diabetes Mellitus (DM), Insulin delivery

Full Text:



Mukherjee B, Paul P, Choudhury A, Bhattacharya S, Maji R, Dutta L. Variation of pharmacokinetic profiles of some antidiabetic drugs from nanostructured formulations administered through pulmonary route. Curr Drug Metab. 2015.

Global report on diabetes WHO Library Cataloguing-in-Publication Data. ISBN;978:92-4.

Kaveeshwar SA, Cornwall J. The current state of diabetes mellitus in India. Australas Med J. Australasian Medical Journal. 2014;7(1):45-8.

Rosenfeld L. Insulin: discovery and controversy. Clin Chem. 2002;48(12):2270-88.

Al-Tabakha MM, Arida AI. Recent challenges in insulin delivery systems: a review. Indian J Pharm Sci. Medknow Publications; 2008;70(3):278-86.

Insulin Administration. Diabetes Care. 2003;26(11):3080-6.

Wheeler BJ, Heels K, Donaghue KC, Reith DM, Ambler GR. Insulin pump-associated adverse events in children and adolescents- a prospective study. Diabetes Technol Ther. 2014;16(9):558-62.

Heinemann L, Fleming GA, Petrie JR, Holl RW, Bergenstal RM, Peters AL. Insulin pump risks and benefits: a clinical appraisal of pump safety standards, adverse event reporting and research needs. A joint statement of the European Association for the Study of Diabetes and the American Diabetes Association Diabetes Technology W. Diabetologia. 2015;58(5):862-70.

Selam JL. Evolution of diabetes insulin delivery devices. J Diabetes Sci Technol. Diabetes Technology Society. 2010;4(3):505-13.

Penfornis A, Personeni E, Borot S. Evolution of Devices in Diabetes Management. Diabetes Technol Ther. 2011;13(S1):S93-102.

Xue L, Mikkelsen KH. Dose accuracy of a durable insulin pen with memory function, before and after simulated lifetime use and under stress conditions. Expert Opin Drug Deliv. 2013;10(3):301-6.

Garg S, Bailey T, DeLuzio T, Pollom D. Preference for a new prefilled insulin pen compared with the original pen. Curr Med Res Opin. 2011;27(12):2323-33.

Pfützner A, Bailey T, Campos C, Kahn D, Ambers E, Niemeyer M, et al. Accuracy and preference assessment of prefilled insulin pen versus vial and syringe with diabetes patients, caregivers, and healthcare professionals. Curr Med Res Opin. 2013;29(5):475-81.

Heinemann L. New ways of insulin delivery. Int J Clin Pract Suppl. 2010;(166):29-40.

Carino GP, Mathiowitz E. Oral insulin delivery1Abbreviations: GI, gastrointestinal; IDDM, insulin-dependent diabetes mellitus; IU, international units; NIDDM, non-insulin-dependent diabetes mellitus; PIN, phase inversion nanoencapsulation; ZOT, zona occludens toxin.1. Adv Drug Deliv Rev. 1999;35(2-3):249-57.

Pauletti GM, Gangwar S, Knipp GT, Nerurkar MM, Okumu FW, Tamura K, et al. Structural requirements for intestinal absorption of peptide drugs. J Control Release. 1996;41(1-2):3-17.

Mesiha M, Plakogiannis F, Vejosoth S. Enhanced oral absorption of insulin from desolvated fatty acid-sodium glycocholate emulsions. Int J Pharm. 1994;111(3):213-6.

Touitou E, Rubinstein A. Targeted enteral delivery of insulin to rats. Int J Pharm. 1986;30(2-3):95-9.

Kohane DS. Microparticles and nanoparticles for drug delivery. Biotechnol Bioeng. 2007;96(2):203-9.

Skyler JS, Cefalu WT, Kourides IA, Landschulz WH, Balagtas CC, Cheng SL, et al. Efficacy of inhaled human insulin in type 1 diabetes mellitus: a randomised proof-of-concept study. Lancet. Elsevier; 2001;357(9253):331-5.

Strack TR. Inhaled human insulin. Drugs of Today. 2006;42(4):207.

Dunn C, Curran MP. Inhaled human insulin (Exubera): a review of its use in adult patients with diabetes mellitus. Drugs. 2006;66(7):1013-32.

Hegewald M, Crapo RO, Jensen RL. Pulmonary function changes related to acute and chronic administration of inhaled insulin. Diabetes Technol Ther. Mary Ann Liebert, Inc. 2 Madison Avenue Larchmont, NY 10538 USA. 2007;9(1):S93-101.

Mudaliar S, Henry RR. Inhaled Insulin in Patients with Asthma and Chronic Obstructive Pulmonary Disease. Diabetes Technol Ther. Mary Ann Liebert, Inc. 2 Madison Avenue Larchmont, NY 10538 USA. 2007;9(1):S83-92.

Nuffer W, Trujillo JM, Ellis SL. Technosphere insulin (Afrezza): A new, inhaled prandial insulin. Ann Pharmacother. 2015;49(1):99-106.

Ledet G, Graves RA, Bostanian LA, Mandal TK. A second-generation inhaled insulin for diabetes mellitus. Am J Health Syst Pharm. 2015;72(14):1181-7.

Fonte P, Araújo F, Silva C, Pereira C, Reis S, Santos HA, et al. Polymer-based nanoparticles for oral insulin delivery: Revisited approaches. Biotechnol Adv. 2015;33:1342-54.

Abbad S, Zhang Z, Waddad AY, Munyendo WLL, Lv H, Zhou J. Chitosan-Modified Cationic Amino Acid Nanoparticles as a Novel Oral Delivery System for Insulin. J Biomed Nanotechnol. 2015;11(3):486-99.

Santos AC, Cunha J, Veiga F, Cordeiro-da-Silva A, Ribeiro AJ. Ultrasonication of insulin-loaded microgel particles produced by internal gelation: impact on particle’s size and insulin bioactivity. Carbohydr Polym. 2013;98(2):1397-408.

Nolan CM, Serpe MJ, Lyon LA. Thermally Modulated Insulin Release from Microgel Thin Films. Biomacromolecules. American Chemical Society; 2004;5(5):1940-6.

Maroni A, Zema L, Del Curto MD, Foppoli A, Gazzaniga A. Oral colon delivery of insulin with the aid of functional adjuvants. Adv Drug Deliv Rev. 2012;64(6):540-56.

Botz CK, Leibel BS, Zingg W, Gander RE, Albisser AM. Comparison of peripheral and portal routes of insulin infusion by a computer-controlled insulin infusion system (artificial endocrine pancreas). Diabetes. 1976;25(8):691-700.

van Dijk PR. CIPII Intraperitoneal insulin.; 2016.

Renard E. Insulin delivery route for the artificial pancreas: subcutaneous, intraperitoneal, or intravenous? Pros and cons. J Diabetes Sci Technol. 2008;2(4):735-8.

Gin H, Renard E, Melki V, Boivin S, Schaepelynck-Bélicar P, Guerci B, et al. Combined improvements in implantable pump technology and insulin stability allow safe and effective long term intraperitoneal insulin delivery in type 1 diabetic patients: the EVADIAC experience. Diabetes Metab. 2003;29(6):602-7.

Kumareswaran K, Evans ML, Hovorka R. Closed-loop insulin delivery: towards improved diabetes care. Discov Med. 2012;13(69):159-70.

Yaturu S. Insulin therapies: Current and future trends at dawn. World J Diabetes. Baishideng Publishing Group Inc. 2013;4(1):1-7.

Leary AC, Stote RM, Cussen K, O’brien J, Leary WP, Buckley B. Pharmacokinetics and Pharmacodynamics of Intranasal Insulin Administered to Patients with Type 1 Diabetes: A Preliminary Study. Diabetes Technol Ther. 2006;8(1):81-8.

Illum L. Nasal drug delivery - Recent developments and future prospects. J Control Release. 2012;161(2):254-63.

Stote R, Marbury T, Shi L, Miller M, Strange P. Comparison pharmacokinetics of two concentrations (0.7% and 1.0%) of Nasulin, an ultra-rapid-acting intranasal insulin formulation. J Diabetes Sci Technol. 2010;4(3):603-9.

Benedict C, Frey WH, Schiöth HB, Schultes B, Born J, Hallschmid M. Intranasal insulin as a therapeutic option in the treatment of cognitive impairments. Exp Gerontol. 2011;46(2-3):112-5.

Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012;69(1):29-38.