Insulin therapy is an integral part of the pharmacological management of Type 2 diabetes mellitus. Guidelines recommended insulin therapy for those patients with suboptimal glycaemic control despite optimal medical treatments. Studies show that insulin therapy with the human and regular insulins improve glycaemic control, reduce the chronic complications, and inevitably improve patient’s quality of life. The new analogue insulin has a better safety profile and efficacies, and has been shown to achieve better outcomes and patient’s acceptability compared with the human and regular insulins. The diabetic guidelines also recommend the intensity of insulin therapy in a personalised glycaemic control strategy based on the patient’s profiles and their preferences. However, the guidelines do not recommend any standardised approach to the principles of insulin initiation, titration, and monitoring. This review summarises the essential principles of insulin initiation, titration, and monitoring in Type 2 diabetes mellitus.
References
[1]
Rosenfeld, L. (2002) Insulin: Discovery and Controversy. Clinical Chemistry, 48, 2270-2288
[2]
Barszczewski, K., Karaś, R., Biadasiewicz, M., Kulik, H. and Lepich, T. (2023) Sir Frederick Grant Banting—The discoverer of insulin. On the 100th anniversary on the Nobel Prize. Przeglad Epidemiologiczny, 77, 108-118. https://doi.org/10.32394/pe.77.11
[3]
Gerstein, H.C. and Rutty, C.J. (2021) Insulin Therapy: The Discovery That Shaped a Century. Canadian Journal of Diabetes, 45, 798-803. https://doi.org/10.1016/j.jcjd.2021.03.002
[4]
Rubino, A., McQuay, L.J., Gough, S.C., Kvasz, M. and Tennis, P. (2007) Delayed Initiation of Subcutaneous Insulin Therapy after Failure of Oral Glucose-Lowering Agents in Patients with Type 2 Diabetes: A Population-Based Analysis in the UK. Diabetic Medicine: A Journal of the British Diabetic Association, 24, 1412-1418. https://doi.org/10.1111/j.1464-5491.2007.02279.x
[5]
UK Prospective Diabetes Study (UKPDS) Group (1998) Intensive Blood-Glucose Control with Sulphonylureas or Insulin Compared with Conventional Treatment and Risk of Complications in Patients with Type 2 Diabetes (UKPDS 33). Lancet, 352, 837-853
[6]
Shichiri, M., Kishikawa, H., Ohkubo, Y. and Wake, N. (2000) Long-Term Results of the Kumamoto Study on Optimal Diabetes Control in Type 2 Diabetic Patients. Diabetes Care, 23, B21-B29
[7]
Chlup, R., Zapletalová, J., Seckar, P., Malá, E., Doubravová, B., Táncosová, S., Chlupová, L., Pukowietz, L. and Zatloukal, P. (2007) Benefits of Complementary Therapy with Insulin Aspart versus Human Regular Insulin in Persons with Type 2 Diabetes Mellitus. Diabetes Technology & Therapeutics, 9, 223-231. https://doi.org/10.1089/dia.2006.0018
[8]
Rosenstock, J., Schwartz, S.L., Clark Jr., C.M., Park, G.D., Donley, D.W. and Edwards, M.B. (2001) Basal Insulin Therapy in Type 2 Diabetes: 28-Week Comparison of Insulin Glargine (HOE 901) and NPH Insulin. Diabetes Care, 24, 631-636. https://doi.org/10.2337/diacare.24.4.631
[9]
Garber, A.J., King, A.B., Del Prato, S., Sreenan, S., Balci, M.K., Muñoz-Torres, M., Rosenstock, J., Endahl, L.A., Francisco, A.M., Hollander, P. and NN1250-3582 (BEGIN BB T2D) Trial Investigators (2012) Insulin Degludec, an Ultra-Long Acting Basal Insulin, versus Insulin Glargine in Basal-Bolus Treatment with Mealtime Insulin Aspart in Type 2 Diabetes (BEGIN Basal-Bolus Type 2): A Phase 3, Randomised, Open-Label, Treat-to-Target Non-Inferiority Trial. Lancet, 379, 1498-1507. https://doi.org/10.1016/S0140-6736(12)60205-0
[10]
Inzucchi, S.E., Bergenstal, R.M., Buse, J.B., et al. (2015) Management of Hyperglycaemia in Type 2 Diabetes, 2015: A Patient Centered Approach: Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 38, 140-149.
[11]
ElSayed, N.A., Aleppo, G., Aroda, V.R., Bannuru, R.R., Brown, F.M., Bruemmer, D., Collins, B.S., Hilliard, M.E., Isaacs, D., Johnson, E.L., Kahan, S., Khunti, K., Leon, J., Lyons, S.K., Perry, M.L., Prahalad, P., Pratley, R.E., Seley, J.J., Stanton, R.C. and Gabbay, R.A. (2023) 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2023. Diabetes Care, 46, S140-S157. https://doi.org/10.2337/dc23-S009
[12]
Davies, M. J., D’Alessio, D.A., Fradkin, J., Kernan, W.N., Mathieu, C., Mingrone, G., Rossing, P., Tsapas, A., Wexler, D.J. and Buse, J.B. (2018) 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). Diabetes Care, 41, 2669-2701. https://doi.org/10.2337/dci18-0033
[13]
Leslie, B.K. (2023) Essentials of Diabetes Medicine. AuthorHouse, London.
[14]
Ritsinger, V., Malmberg, K., Mårtensson, A., Rydén, L., Wedel, H. and Norhammar, A. (2014) Intensified Insulin-Based Glycaemic Control after Myocardial Infarction: Mortality during 20-Year Follow-Up of the Randomised Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI 1) Trial. The Lancet, Diabetes & Endocrinology, 2, 627-633. https://doi.org/10.1016/S2213-8587(14)70088-9
[15]
Jianping, W., Yanbing, L.I., Wen, X.U., et al. (2008) Effect of Intensive Insulin Therapy on Beta-Cell Function and Glycaemic Control in Patients with Newly Diagnosed Type 2 Diabetes: A Multicentre Randomised Parallel-Group Trial. Lancet, 371, 1753-1760. https://doi.org/10.1016/S0140-6736(08)60762-X
[16]
Kong, M.F. (2011) Insulin Should Be Prescribed at the Outset of Diagnosis of Type 2 Diabetes. Practical Diabetes International, 28, 85-87b. https://doi.org/10.1002/pdi.1564
[17]
Holman, R.R., Thorne, K.I., Farmer, A.J., Davies, M.J., Keenan, J.F., Paul, S., Levy, J.C. and 4-T Study Group (2007) Addition of Biphasic, Prandial, or Basal Insulin to Oral Therapy in Type 2 Diabetes. The New England Journal of Medicine, 357, 1716-1730. https://doi.org/10.1056/NEJMoa075392
[18]
National Institute for Health and Care Excellence (2022) Type 2 Diabetes in Adults: Management. https://www.nice.org.uk/guidance/ng28/resources/type-2-diabetes-in-adults-management-pdf-1837338615493
[19]
Scottish Intercollegiate Network Guideline (2017) Management of Diabetes: 116 A National Clinical Guideline. https://www.sign.ac.uk/assets/sign116.pdf
[20]
Khunti, K., Mohan, V., Jain, S.M., Boesgaard, T.W., Begtrup, K. and Sethi, B. (2017) Efficacy and Safety of IDegLira in Participants with Type 2 Diabetes in India Uncontrolled on Oral Antidiabetic Drugs and Basal Insulin: Data from the DUAL Clinical Trial Program. Diabetes Therapy: Research, Treatment and Education of Diabetes and Related Disorders, 8, 673-682. https://doi.org/10.1007/s13300-017-0252-9
[21]
Lovre, D. and Fonseca, V. (2015) Benefits of Timely Basal Insulin Control in Patients with Type 2 Diabetes. Journal of Diabetes and Its Complications, 29, 295-301. https://doi.org/10.1016/j.jdiacomp.2014.11.018
[22]
Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein, H.C., Miller, M.E., Byington, R.P., Goff, D.C., Bigger Jr., J.T., Buse, J.B., Cushman, W.C., Genuth, S., Ismail-Beigi, F., Grimm, R.H., Probstfield Jr., J.L., Simons-Morton, D. G. and Friedewald, W.T. (2008) Effects of Intensive Glucose Lowering in Type 2 Diabetes. The New England Journal of Medicine, 358, 2545-2559. https://doi.org/10.1056/NEJMoa0802743
[23]
Rubino, A., McQuay, L.J., Gough, S.C., Kvasz, M. and Tennis, P. (2007) Delayed Initiation of Subcutaneous Insulin Therapy after Failure of Oral Glucose-Lowering Agents in Patients with Type 2 Diabetes: A Population-Based Analysis in the UK. Diabetic Medicine: A Journal of the British Diabetic Association, 24, 1412-1418. https://doi.org/10.1111/j.1464-5491.2007.02279.x
[24]
Bretzel, R.G., Nuber, U., Landgraf, W., Owens, D.R., Bradley, C. and Linn, T. (2008) Once-Daily Basal Insulin Glargine versus Thrice-Daily Prandial Insulin Lispro in People with Type 2 Diabetes on Oral Hypoglycaemic Agents (APOLLO): An Open Randomised Controlled Trial. Lancet, 371, 1073-1084. https://doi.org/10.1016/S0140-6736(08)60485-7
[25]
Nathan, D.M., Buse, J.B., Davidson, M.B., Heine, R.J., Holman, R.R., Sherwin, R. and Zinman, B. (2006) Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A Consensus Statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 29, 1963-1972. https://doi.org/10.2337/dc06-9912
[26]
Riddle, M.C., Bolli, G.B., Ziemen, M., Muehlen-Bartmer, I., Bizet, F. and Home, P.D. (2014) New Insulin Glargine 300 Units/mL versus Glargine 100 Units/mL in People with Type 2 Diabetes Using Basal and Mealtime Insulin: Glucose Control and Hypoglycemia in a 6-Month Randomized Controlled Trial (EDITION 1) Diabetes Care, 37, 2755-2762. https://doi.org/10.2337/dc14-0991
[27]
Lamos, E.M., Younk, L.M. and Davis, S.N. (2016) Concentrated Insulins: The New Basal Insulins. Therapeutics and Clinical Risk Management, 12, 389-400. https://doi.org/10.2147/TCRM.S99855
[28]
Keating G.M. (2013) Insulin Degludec and Insulin Degludec/Insulin Aspart: A Review of Their Use in the Management of Diabetes Mellitus. Drugs, 73, 575-593. https://doi.org/10.1007/s40265-013-0051-1
[29]
Miser, W.F., Arakaki, R., Jiang, H., Scism-Bacon, J., Anderson, P.W. and Fahrbach, J.L. (2010) Randomized, Open-Label, Parallel-Group Evaluations of Basal-Bolus Therapy versus Insulin Lispro Premixed Therapy in Patients with Type 2 Diabetes Mellitus Failing to Achieve Control with Starter Insulin Treatment and Continuing Oral Antihyperglycemic Drugs: A Noninferiority Intensification Sub Study of the DURABLE Trial. Clinical Therapeutics, 32, 896-908. https://doi.org/10.1016/j.clinthera.2010.05.001
[30]
Jia, W., Xiao, X., Ji, Q., Ahn, K.J., Chuang, L.M., Bao, Y., Pang, C., Chen, L., Gao, F., Tu, Y., Li, P. and Yang, J. (2015) Comparison of Thrice-Daily Premixed Insulin (Insulin Lispro Premix) with Basal-Bolus (Insulin Glargine Once-Daily Plus Thrice-Daily Prandial Insulin Lispro) Therapy in East Asian Patients with Type 2 Diabetes Insufficiently Controlled with Twice-Daily Premixed Insulin: An Open-Label, Randomised, Controlled Trial. The Lancet, Diabetes & Endocrinology, 3, 254-262. https://doi.org/10.1016/S2213-8587(15)00041-8
[31]
Ashwell, S.G., Amiel, S.A., Bilous, R.W., Dashora, U., Heller, S.R., Hepburn, D.A., Shutler, S.D., Stephens, J.W. and Home, P.D. (2006) Improved Glycaemic Control with Insulin Glargine Plus Insulin Lispro: A Multicentre, Randomized, Cross-Over Trial in People with Type 1 Diabetes. Diabetic Medicine: A Journal of the British Diabetic Association, 23, 285-292. https://doi.org/10.1111/j.1464-5491.2005.01781.x
[32]
Balena, R., Hensley, I.E., Miller, S. and Barnett, A.H. (2013) Combination Therapy with GLP-1 Receptor Agonists and Basal Insulin: A Systematic Review of the Literature. Diabetes, Obesity & Metabolism, 15, 485-502. https://doi.org/10.1111/dom.12025
[33]
Yoon, N.M., Cavaghan, M.K., Brunelle, R.L. and Roach, P. (2009) Exenatide Added to Insulin Therapy: A Retrospective Review of Clinical Practice over Two Years in an Academic Endocrinology Outpatient Setting. Clinical Therapeutics, 31, 1511-1523. https://doi.org/10.1016/j.clinthera.2009.07.021
[34]
Mudaliar, S. and Henry, R.R. (2010) Effects of Incretin Hormones on Beta-Cell Mass and Function, Body Weight, and Hepatic and Myocardial Function. The American Journal of Medicine, 123, S19-S27. https://doi.org/10.1016/j.amjmed.2009.12.006
[35]
Drucker D.J. (2006) The Biology of Incretin Hormones. Cell Metabolism, 3, 153-165. https://doi.org/10.1016/j.cmet.2006.01.004
[36]
Chinese Society of Endocrinology, Chinese Diabetes Society, Chinese Endocrinologist Association. (2021) China Insulin Pump Clinical Guideline (2021). Chinese Journal of Endocrinology and Metabolism, 37, 679-701. (In Chinese)
[37]
Diabetes Control and Complications Trial Research Group, Nathan, D.M., Genuth, S., Lachin, J., Cleary, P., Crofford, O., Davis, M., Rand, L. and Siebert, C. (1993) The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus. The New England Journal of Medicine, 329, 977-986. https://doi.org/10.1056/NEJM199309303291401
[38]
Reichard, P., Nilsson, B.Y. and Rosenqvist, U. (1993) The Effect of Long-Term Intensified Insulin Treatment on the Development of Microvascular Complications of Diabetes Mellitus. The New England Journal of Medicine, 329, 304-309. https://doi.org/10.1056/NEJM199307293290502
[39]
ADVANCE Collaborative Group, Patel, A., MacMahon, S., Chalmers, J., Neal, B., Billot, L., Woodward, M., Marre, M., Cooper, M., Glasziou, P., Grobbee, D., Hamet, P., Harrap, S., Heller, S., Liu, L., Mancia, G., Mogensen, C. E., Pan, C., Poulter, N., Rodgers, A., et al. (2008) Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes. The New England Journal of Medicine, 358, 2560-2572. https://doi.org/10.1056/NEJMoa0802987
[40]
U.K. Prospective Diabetes Study Group (1995) U.K. Prospective Diabetes Study 16: Overview of 6 Years’ Therapy of Type II Diabetes: A Progressive Disease. Diabetes, 44, 1249-1258. https://doi.org/10.2337/diab.44.11.1249