Newer and Future Insulins
Abstract
The management of Diabetes was revolutionised by discovery of insulin. However the insulin delivery as well action profile of initial insulins were far from physiological. The initial insulins were replaced by recombinant insulins and later by insulin analogues. Further refinements in insulin therapy are aimed at making these analogues more physiological, minimise risk of
hypoglycaemia, making delivery timing more flexible, reduce/avoid need for injections etc. The review summarises the recently available insulin analogues as well as few advances in the pipeline.
References
1. International Diabetes Federation. About diabetes. Available at: http://www.idf.org/about-diabetes Accessed Jan 9, 2013.
2. Evans M, Schumm-Draeger PM, Vora J et al. A review of modern insulin analogue pharmacokinetic and pharmacodynamic profiles in type 2 diabetes: improvements and limitations. Diabetes Obes Metab. 2011;13:677-684.
3. Goykhman S, Drincic A, Desmangles JC, Rendell M. Insulin Glargine: a review 8 years after its introduction. Expert OpinPharmacother.2009; 10:705–718.
4. Heinemann L, Linkeschova R, Rave K et al. Time-action profile of the long-acting insulin analog insulinglargine (HOE901) in comparison with those of NPH insulin and placebo. Diab Care. 2000; 23:644–649.
5. Bolli GB, Riddle MC, Bergenstal RM et al. New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin-naïve people with type 2 diabetes on oral glucoselowering drugs: a randomized controlled trial (EDITION 3). Diabetes ObesMetab. 2015; 17:386.
6. Yki-Järvinen H, Bergenstal R, Ziemen M, et al. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using oral agents and basal insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 2). Diabetes Care. 2014; 37:3235
7. Pandyarahan V, Weiss MA. Design of Non-Standard Insulin Analogs for the Treatment of Diabetes Mellitus.CurrDiab Rep 2012; 12: 697-704
8. Wang F, Surh J, Kaur M. Insulin degludec as an ultralongacting basal insulin once a day: a systematic review. Diabetes Metab Syndr Obes. 2012;5:191-204.
9. Heise T, Nosek L, Coester HV, et al. Steady state is reached within two to three days of once-daily administration of ultra-long-acting insulin degludec. Program and abstract of the American Diabetes Association 72nd Scientific Sessions; June 8-12, 2012; Philadelphia, PA. Abstract 1013-P
10. Heise T, Nosek L, Bøttcher SG et al. Ultra-long-acting insulin degludec has a at and stable glucose-lowering e ect in type 2 diabetes. Diabetes Obes Metab.2012;14(10):944-950.
11. Heller SR, Mathieu C, Kapur R, Wolden ML, Zinman B. Rate ratios for nocturnal confirmed hypoglycemia with insulin
degludec vs. insulin glargine using different definitions. Diabetes. 2014; 63(Suppl. 1): A106, abstract 402-P
12. Davies M, Sasaki T, Gross JL, Bantwal G, Ono Y, Nishida T et al. Comparison of insulin degludec with insulin detemir in type 1 diabetes: a 1-year treat-to-target trial. Diabetes Obes Metab. 2015 Sep 7.doi: 10.1111/dom.12573. [Epub ahead of print])
13. Korsatko S, Deller S et al. Ultra-Long-Acting Insulin Degludec: Two Different Formulations (U100 and U200) Are Bioequivalent and Show Similar Pharmacodynamics. Poster presentation 2349-PO, 2011.ADA Scientific Meeting.
14. Gough SCL, BhargavaA et al. Low-Volume insulin degludec 200 units/mL once daily improves glycemic control similar to insulin glargine with a low risk of hypoglycemia in insulin naïve patients with type 2 diabetes. Diab Care. 2013;36:2536- 42
15. Jacober S J, Rosenstock J, Bergenstal RM, PrinceM J, Qu Y, Beals JM. Contrasting weight changes with LY2605541, a novel long-acting insulin, and insulin glargine despite
similar improvedglycaemic control in T1DM and T2DM. DiabObesity Metab. 2014;16:351–356
16. Caparrotta TM, Evans M. PEGylated insulin Lispro, (LY2605541)-a new basal insulin analogue. Diabetes Obes Metab. 2014 May;16(5):388-95
17. Bergenstal RM, Rosenstock J, Arakaki RF, Prince MJ, Qu Y, Sinha VP, Howey DC, Jacober SJ. A randomized, controlled study of once-daily LY2605541, a novel long-acting basal insulin, versus insulin glargine in basal insulin-treated patients with type 2 diabetes. Diabetes Care.2012 Nov;35(11):2140-7
18. A Study of Insulin Peglispro (LY2605541) in Participants With Type 2 Diabetes Mellitus. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited2015 Oct 27]. Available from: https://clinicaltrials.gov/ ct2/show/NCT02106364
19. Translational Research Institute for Metabolism and Diabetes, Florida. Effects and Response of LY2605541 in Patients With Type 1 Diabetes Mellitus (BIDO). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Oct 28]. Available from: https://www. clinicaltrials.gov/ct2/show/NCT02211586
20. Brange J. The new era of biotech insulin analogues. Diabetologia. 1997; 40:S48–S53.
21. Brems DN, Alter LA, Beckage MJ et al. Altering the association properties of insulin by amino acid replacement. Protein Eng. 1992; 5:527–533.
22. Peyrot M, Rubin RR, Lauritzen T, SkovlundSE, Snoek FJ, Matthews DR et al. International DAWN Advisory Panel. Resistance to insulin therapy among patients and providers: results of the cross-national Diabetes Attitudes, Wishes, and Needs (DAWN) study.
23. Neumiller JJ, Campbell RK. Technosphere® Insulin: an inhaled prandial insulin product. BioDrugs.2010;24(3):165-72.
24. MannKind Corporation. Clinical Trial Evaluating Technosphere® Insulin Versus Insulin Aspart in Subjects With Type 1 Diabetes Mellitus Over a 24-week Treatment Period. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Oct 25]. Available from:https://clinicaltrials.gov/ct2/show/ NCT01445951
25. Director, Clinical Trial Disclosure Group, Pfizer, Inc. Long- Term Safety Study Of Inhaled Insulin (CP-464,005, Inhaler) In Japanese Patients With Type1 or Type2 Diabetes. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Oct 26]. Available from:https://clinicaltrials.gov/ct2/show/NCT00527397
26. Oramed, Ltd. Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Multiple Oral Bedtime Doses of 2 in Adult Patients With Type 2 Diabetes Mellitus (T2DM). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Oct 26]. Available from: https://clinicaltrials.gov/ct2/show/NCT01889667
27. Oral Insulin: A Comparison with Subcutaneous Regular Human Insulin in Patients With Type 2 Diabetes. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Oct 26]. Available from: https://clinicaltrials.gov/ct2/show/NCT00982254
28. Effectiveness of Oral Insulin in Unstable Type 1 Diabetes Patients. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Oct 26]. Available from: https://clinicaltrials.gov/ct2/show/ NCT00867594.
29. The University of Texas Health Science Center at San Antonio. A Euglycemic Insulin Clamp Study in Type 1 Diabetic Patients With Oral Insulin (ORAMED). In: ClinicalTrials. gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 26 Oct]. Available from: https://clinicaltrials. gov/ct2/show/NCT02535715.
30. Oshadi Drug Administration. Safety and Efficacy of Single Administration of Oshadi Oral Insulin in Type I Diabetes Patients. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Oct 26]. Available from: https://clinicaltrials.gov/ct2/show/study/ NCT01120912.
31. Aimee J, Joseph A. Insulin and its analogues and their affinities for the IGF1 receptor. Endocrine-Related Cancer (2012) 19 F63–F75.
32. David R, Wolfgang L, Andrea S, Reinhard G, Martin K. The Emergence of Biosimilar Insulin Preparations—A Cause for Concern?.Diab Tech Therap. 2012;1411.
33. European Medicines Agency: Pre-authorisation evaluation of medicines for human use: withdrawal assessment reportfor insulin human 30/70 Mix Marvel. EMEA/ CHMP/ 70179/2008. www.ema.europa.eu/docs/en_ GB/document_library/Application_withdrawal_assessment_ report/2010/ 01/WC500067169.pdf (accessed August 2012).
34. European Medicines Agency: Pre-authorisation evaluation of medicines for human use: withdrawal assessment report for insulin human Long Marvel. EMEA/ CHMP/70349/2008.www.ema.europa.eu/docs/en_GB/ document_library/Application_withdrawal_assessment_ report/2010/01/WC500067170pdf(accessed August 2012).
35. European Medicines Agency: Pre-authorisation evaluation of medicines for human use: withdrawal assessment report for insulin human Rapid Marvel. EMEA/ CHMP/317778/ 2007. www.ema.europa.eu/docs/en_ GB/document_library/Application_withdrawal_assessment_ report/2010/01/ WC500067086.pdf (accessed August 2012).
36. European Medicines Agency Press Release: Marvel Life- Sciences Ltd withdraws its marketing authorisationappli- cations for Insulin Human Rapid Marvel, Insulin Human Long Marvel and Insulin Human 30/70 Mix Marvel.EMEA/ 2435/2008.www.ema.europa.eu/ docs/en_GB/document_library/Press_release/2009/11/ WC500015335.pdf (accessed August 2012).
2. Evans M, Schumm-Draeger PM, Vora J et al. A review of modern insulin analogue pharmacokinetic and pharmacodynamic profiles in type 2 diabetes: improvements and limitations. Diabetes Obes Metab. 2011;13:677-684.
3. Goykhman S, Drincic A, Desmangles JC, Rendell M. Insulin Glargine: a review 8 years after its introduction. Expert OpinPharmacother.2009; 10:705–718.
4. Heinemann L, Linkeschova R, Rave K et al. Time-action profile of the long-acting insulin analog insulinglargine (HOE901) in comparison with those of NPH insulin and placebo. Diab Care. 2000; 23:644–649.
5. Bolli GB, Riddle MC, Bergenstal RM et al. New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin-naïve people with type 2 diabetes on oral glucoselowering drugs: a randomized controlled trial (EDITION 3). Diabetes ObesMetab. 2015; 17:386.
6. Yki-Järvinen H, Bergenstal R, Ziemen M, et al. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using oral agents and basal insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 2). Diabetes Care. 2014; 37:3235
7. Pandyarahan V, Weiss MA. Design of Non-Standard Insulin Analogs for the Treatment of Diabetes Mellitus.CurrDiab Rep 2012; 12: 697-704
8. Wang F, Surh J, Kaur M. Insulin degludec as an ultralongacting basal insulin once a day: a systematic review. Diabetes Metab Syndr Obes. 2012;5:191-204.
9. Heise T, Nosek L, Coester HV, et al. Steady state is reached within two to three days of once-daily administration of ultra-long-acting insulin degludec. Program and abstract of the American Diabetes Association 72nd Scientific Sessions; June 8-12, 2012; Philadelphia, PA. Abstract 1013-P
10. Heise T, Nosek L, Bøttcher SG et al. Ultra-long-acting insulin degludec has a at and stable glucose-lowering e ect in type 2 diabetes. Diabetes Obes Metab.2012;14(10):944-950.
11. Heller SR, Mathieu C, Kapur R, Wolden ML, Zinman B. Rate ratios for nocturnal confirmed hypoglycemia with insulin
degludec vs. insulin glargine using different definitions. Diabetes. 2014; 63(Suppl. 1): A106, abstract 402-P
12. Davies M, Sasaki T, Gross JL, Bantwal G, Ono Y, Nishida T et al. Comparison of insulin degludec with insulin detemir in type 1 diabetes: a 1-year treat-to-target trial. Diabetes Obes Metab. 2015 Sep 7.doi: 10.1111/dom.12573. [Epub ahead of print])
13. Korsatko S, Deller S et al. Ultra-Long-Acting Insulin Degludec: Two Different Formulations (U100 and U200) Are Bioequivalent and Show Similar Pharmacodynamics. Poster presentation 2349-PO, 2011.ADA Scientific Meeting.
14. Gough SCL, BhargavaA et al. Low-Volume insulin degludec 200 units/mL once daily improves glycemic control similar to insulin glargine with a low risk of hypoglycemia in insulin naïve patients with type 2 diabetes. Diab Care. 2013;36:2536- 42
15. Jacober S J, Rosenstock J, Bergenstal RM, PrinceM J, Qu Y, Beals JM. Contrasting weight changes with LY2605541, a novel long-acting insulin, and insulin glargine despite
similar improvedglycaemic control in T1DM and T2DM. DiabObesity Metab. 2014;16:351–356
16. Caparrotta TM, Evans M. PEGylated insulin Lispro, (LY2605541)-a new basal insulin analogue. Diabetes Obes Metab. 2014 May;16(5):388-95
17. Bergenstal RM, Rosenstock J, Arakaki RF, Prince MJ, Qu Y, Sinha VP, Howey DC, Jacober SJ. A randomized, controlled study of once-daily LY2605541, a novel long-acting basal insulin, versus insulin glargine in basal insulin-treated patients with type 2 diabetes. Diabetes Care.2012 Nov;35(11):2140-7
18. A Study of Insulin Peglispro (LY2605541) in Participants With Type 2 Diabetes Mellitus. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited2015 Oct 27]. Available from: https://clinicaltrials.gov/ ct2/show/NCT02106364
19. Translational Research Institute for Metabolism and Diabetes, Florida. Effects and Response of LY2605541 in Patients With Type 1 Diabetes Mellitus (BIDO). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Oct 28]. Available from: https://www. clinicaltrials.gov/ct2/show/NCT02211586
20. Brange J. The new era of biotech insulin analogues. Diabetologia. 1997; 40:S48–S53.
21. Brems DN, Alter LA, Beckage MJ et al. Altering the association properties of insulin by amino acid replacement. Protein Eng. 1992; 5:527–533.
22. Peyrot M, Rubin RR, Lauritzen T, SkovlundSE, Snoek FJ, Matthews DR et al. International DAWN Advisory Panel. Resistance to insulin therapy among patients and providers: results of the cross-national Diabetes Attitudes, Wishes, and Needs (DAWN) study.
23. Neumiller JJ, Campbell RK. Technosphere® Insulin: an inhaled prandial insulin product. BioDrugs.2010;24(3):165-72.
24. MannKind Corporation. Clinical Trial Evaluating Technosphere® Insulin Versus Insulin Aspart in Subjects With Type 1 Diabetes Mellitus Over a 24-week Treatment Period. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Oct 25]. Available from:https://clinicaltrials.gov/ct2/show/ NCT01445951
25. Director, Clinical Trial Disclosure Group, Pfizer, Inc. Long- Term Safety Study Of Inhaled Insulin (CP-464,005, Inhaler) In Japanese Patients With Type1 or Type2 Diabetes. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Oct 26]. Available from:https://clinicaltrials.gov/ct2/show/NCT00527397
26. Oramed, Ltd. Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Multiple Oral Bedtime Doses of 2 in Adult Patients With Type 2 Diabetes Mellitus (T2DM). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Oct 26]. Available from: https://clinicaltrials.gov/ct2/show/NCT01889667
27. Oral Insulin: A Comparison with Subcutaneous Regular Human Insulin in Patients With Type 2 Diabetes. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Oct 26]. Available from: https://clinicaltrials.gov/ct2/show/NCT00982254
28. Effectiveness of Oral Insulin in Unstable Type 1 Diabetes Patients. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Oct 26]. Available from: https://clinicaltrials.gov/ct2/show/ NCT00867594.
29. The University of Texas Health Science Center at San Antonio. A Euglycemic Insulin Clamp Study in Type 1 Diabetic Patients With Oral Insulin (ORAMED). In: ClinicalTrials. gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 26 Oct]. Available from: https://clinicaltrials. gov/ct2/show/NCT02535715.
30. Oshadi Drug Administration. Safety and Efficacy of Single Administration of Oshadi Oral Insulin in Type I Diabetes Patients. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Oct 26]. Available from: https://clinicaltrials.gov/ct2/show/study/ NCT01120912.
31. Aimee J, Joseph A. Insulin and its analogues and their affinities for the IGF1 receptor. Endocrine-Related Cancer (2012) 19 F63–F75.
32. David R, Wolfgang L, Andrea S, Reinhard G, Martin K. The Emergence of Biosimilar Insulin Preparations—A Cause for Concern?.Diab Tech Therap. 2012;1411.
33. European Medicines Agency: Pre-authorisation evaluation of medicines for human use: withdrawal assessment reportfor insulin human 30/70 Mix Marvel. EMEA/ CHMP/ 70179/2008. www.ema.europa.eu/docs/en_ GB/document_library/Application_withdrawal_assessment_ report/2010/ 01/WC500067169.pdf (accessed August 2012).
34. European Medicines Agency: Pre-authorisation evaluation of medicines for human use: withdrawal assessment report for insulin human Long Marvel. EMEA/ CHMP/70349/2008.www.ema.europa.eu/docs/en_GB/ document_library/Application_withdrawal_assessment_ report/2010/01/WC500067170pdf(accessed August 2012).
35. European Medicines Agency: Pre-authorisation evaluation of medicines for human use: withdrawal assessment report for insulin human Rapid Marvel. EMEA/ CHMP/317778/ 2007. www.ema.europa.eu/docs/en_ GB/document_library/Application_withdrawal_assessment_ report/2010/01/ WC500067086.pdf (accessed August 2012).
36. European Medicines Agency Press Release: Marvel Life- Sciences Ltd withdraws its marketing authorisationappli- cations for Insulin Human Rapid Marvel, Insulin Human Long Marvel and Insulin Human 30/70 Mix Marvel.EMEA/ 2435/2008.www.ema.europa.eu/ docs/en_GB/document_library/Press_release/2009/11/ WC500015335.pdf (accessed August 2012).
Published
2019-08-07
How to Cite
Diego Espinoza-Peralta, Jorge Rogel-Manzanares. (2019). Newer and Future Insulins. The Indian Practitioner, 68(11), 56-61. Retrieved from https://articles.theindianpractitioner.com/index.php/tip/article/view/536
Section
Review article
