The recent introduction of the second-generation long-acting analogue insulins degludec and insulin glargine U300 have increased the choice of basal insulin therapy for patients with type 2 diabetes. The pharmacokinetic and pharmacodynamic properties of these insulins result in a flatter profile that lasts over 24 h and provides an increased window of administration of 6 h once daily. Large-scale multicentre randomised clinical trial programmes (BEGIN for degludec U100 and U200 and EDITION for glargine U300) evaluating these insulin therapies against glargine U100 have demonstrated that they are either non-inferior or superior for glycaemic efficacy and safety, but less likely to result in severe or nocturnal hypoglycaemia than glargine U100. The disposable pen devices for these insulins have been designed with patient satisfaction and convenience in mind. No concerns have arisen with adverse events with insulin analogues or cardiovascular safety from the ORIGIN and DEVOTE trials. As they demonstrate equivalent glycaemic efficacy to other basal insulins, they should be considered more in selected patient groups including those with recurrent or increased risk of hypoglycaemia, especially severe or nocturnal episodes, in the elderly or those living alone, and in patients with multiple co-morbidities such as cardiovascular or renal disease.
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Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA. Pancreatic extracts in the treatment of diabetes mellitus. Can Med Assoc J. 1922;12(3):141–6.
Herring R, Russell-Jones DDL. Lessons for modern insulin development. Diabet Med. 2018;35(10):1320–8.
Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet. 2017;389(10085):2239–51.
Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia 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. 2015;38(1):140–9.
Holman RR, Farmer AJ, Davies MJ, et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009;361(18):1736–47.
Lipska KJ, Parker MM, Moffet HH, Huang ES, Karter AJ. Association of initiation of basal insulin analogs vs neutral protamine hagedorn insulin with hypoglycemia-related emergency department visits or hospital admissions and with glycemic control in patients with type 2 diabetes. JAMA. 2018;320(1):53–62.
Grunberger G, Chen L, Rodriguez A, Tinahones FJ, Jacober SJ, Bue-Valleskey J. A randomized clinical trial of basal insulin peglispro vs NPH in insulin-naive patients with type 2 diabetes: the IMAGINE 6 trial. Diabetes Obes Metab. 2016;18(Suppl 2):34–42.
Munoz-Garach A, Molina-Vega M, Tinahones FJ. How can a good idea fail? Basal insulin peglispro [LY2605541] for the treatment of type 2 diabetes. Diabetes Ther. 2017;8(1):9–22.
International Diabetes F. IDF diabetes atlas. Brussels: Belgium; 2017.
Standl E, Owen DR. New long-acting basal insulins: does benefit outweigh cost? Diabetes Care. 2016;39(Suppl 2):S172–9.
Josse RG, Woo V. Flexibly timed once-daily dosing with degludec: a new ultra-long-acting basal insulin. Diabetes Obes Metab. 2013;15(12):1077–84.
Woo VC. New insulins and new aspects in insulin delivery. Can J Diabetes. 2015;39(4):335–43.
Goldman J, Kapitza C, Pettus J, Heise T. Understanding how pharmacokinetic and pharmacodynamic differences of basal analog insulins influence clinical practice. Curr Med Res Opin. 2017;33(10):1821–31.
Garber AJ, King AB, Del Prato S, et al. Insulin degludec, an ultra-longacting 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. 2012;379(9825):1498–507.
Zinman B, Philis T, Cariou B, et al. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-target trial (BEGIN Once Long). Diabetes Care. 2012;35(12):2464–71.
Gough SC, Bhargava A, Jain R, et al. Low-volume insulin degludec 200 units/ml once daily improves glycemic control similarly to insulin glargine with a low risk of hypoglycemia in insulinnaive patients with type 2 diabetes: a 26-week, randomized, controlled, multinational, treat-totarget trial: the BEGIN LOW VOLUME trial. Diabetes Care. 2013;36(9):2536–42.
Onishi Y, Iwamoto Y, Yoo SJ, et al. Insulin degludec compared with insulin glargine in insulinnaive patients with type 2 diabetes: a 26-week, randomized, controlled, Pan-Asian, treat-to-target trial. J Diabetes Investig. 2013;4(6):605–12.
Wysham C, Bhargava A, Chaykin L, et al. Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 2 diabetes: the SWITCH 2 randomized clinical trial. JAMA. 2017;318(1):45–56.
Frier BM. How hypoglycaemia can affect the life of a person with diabetes. Diabetes Metab Res Rev. 2008;24(2):87–92.
Hammer M, Lammert M, Mejias SM, Kern W, Frier BM. Costs of managing severe hypoglycaemia in three European countries. J Med Econ. 2009;12(4):281–90.
Sinclair A, Dunning T, Rodriguez-Manas L. Diabetes in older people: new insights and remaining challenges. Lancet Diabetes Endocrinol. 2015;3(4):275–85.
Dalal MR, Kazemi M, Ye F, Xie L. Hypoglycemia after initiation of basal insulin in patients with type 2 diabetes in the united states: implications for treatment discontinuation and healthcare costs and utilization. Adv Ther. 2017;34(9):2083–92.
Ratner RE, Gough SC, Mathieu C, et al. Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2 and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials. Diabetes Obes Metab. 2013;15(2):175–84.
Vora J, Christensen T, Rana A, Bain SC. Insulin degludec versus insulin glargine in type 1 and type 2 diabetes mellitus: a meta-analysis of endpoints in phase 3a trials. Diabetes Ther. 2014;5(2):435–46.
Madenidou AV, Paschos P, Karagiannis T, et al. Comparative benefits and harms of basal insulin analogues for type 2 diabetes: a systematic review and network meta-analysis. Ann Intern Med. 2018;169(3):165–74.
Marso SP, McGuire DK, Zinman B, et al. Efficacy and safety of degludec versus glargine in type 2 diabetes. N Engl J Med. 2017;377(8):723–32.
Becker RH, Nowotny I, Teichert L, Bergmann K, Kapitza C. Low within- and between-day variability in exposure to new insulin glargine 300 U/ml. Diabetes Obes Metab. 2015;17(3):261–7.
Riddle MC, Bolli GB, Zieman M, et al. 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. 2014;37(10):2755–62.
Yki-Jarvinen 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(12):3235–43.
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 glucose-lowering drugs: a randomized controlled trial (EDITION 3). Diabetes Obes Metabol. 2015;17(4):386–94.
Terauchi Y, Koyama M, Cheng X, et al. New insulin glargine 300 U/ml versus glargine 100 U/ml in Japanese people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: glucose control and hypoglycaemia in a randomized controlled trial (EDITION JP 2). Diabetes Obes Metabol. 2016;18(4):366–74.
Ritzel R, Roussel R, Bolli GB, et al. Patient-level meta-analysis of the EDITION 1, 2 and 3 studies: glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus glargine 100 U/ml in people with type 2 diabetes. Diabetes Obes Metab. 2015;17(9):859–67.
Investigators OT, Gerstein HC, Bosch J, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367(4):319–28.
Lonn EM, Bosch J, Diaz R, et al. Effect of insulin glargine and n-3FA on carotid intima-media thickness in people with dysglycemia at high risk for cardiovascular events: the glucose reduction and atherosclerosis continuing evaluation study (ORIGIN-GRACE). Diabetes Care. 2013;36(9):2466–74.
Rosenstock J, Cheng A, Ritzel R, et al. More Similarities than differences testing insulin glargine 300 units/ml versus insulin degludec 100 units/ml in insulin-naive type 2 diabetes: the randomized head-to-head bright trial. Diabetes Care. 2018;41(10):2147–54.
Yamabe M, Kuroda M, Hirosawa Y, Kamino H, Ohno H, Yoneda M. Comparison of insulin glargine 300 U/mL and insulin degludec using flash glucose monitoring: a randomized cross-over study. J Diabetes Investig. 2018. https://doi.org/10.1111/jdi.12894.
Kawaguchi Y, Sawa J, Sakuma N, Kumeda Y. Efficacy and safety of insulin glargine 300 U/mL vs insulin degludec in patients with type 2 diabetes: a randomized, open-label, cross-over study using continuous glucose monitoring profiles. J Diabetes Investig. 2018. https://doi.org/10.1111/jdi.12884.
Sullivan SD, Bailey TS, Roussel R, et al. Clinical outcomes in real-world patients with type 2 diabetes switching from first- to second-generation basal insulin analogues: comparative effectiveness of insulin glargine 300 units/mL and insulin degludec in the DELIVER D+ cohort study. Diabetes Obes Metab. 2018;20(9):2148–58.
Meneghini L, Roussel R, Zhou FL, et al. Comparable Rates of Severe Hypoglycemia in People with Type 2 Diabetes (T2DM) at High Risk of Hypoglycemia Switching to either Insulin Glargine 300 U/mL (Gla-300) or Insulin Degludec (IDeg)—The Lightning Real-World Predictive Modeling Study. American Diabetes Association. Orlando: ADA; 2018.
Sanofi. https://www.toujeo.com/how-to-use-toujeo-insulin. Accessed 25 Sept 2018.
Pohlmeier H, Berard L, Brulle-Wohlhueter C, et al. Ease of use of the insulin glargine 300 U/mL pen injector in insulin-naive people with type 2 diabetes. J Diabetes Sci Technol. 2017;11(2):263–9.
NovoNordisk. https://www.tresibapro.com/dosing-and-device/tresiba-flextouch.html. Accessed 25 Sept 2018.
Bailey T, Campos C. FlexTouch(R) for the delivery of insulin: technical attributes and perception among patients and healthcare professionals. Expert Rev Med Devices. 2012;9(3):209–17.
Pfutzner A, Forst T, Niemeyer M, et al. Assessment for ease of use and preference of a new prefilled insulin pen (FlexTouch Degludec U100/U200) versus the SoloSTAR insulin pen by patients with diabetes and healthcare professionals. Expert Opin Drug Deliv. 2014;1199:1381–9.
Peyrot M, Barnett AH, Meneghini LF, Schumm-Draeger PM. Factors associated with injection omission/non-adherence in the Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabetes Obes Metab. 2012;14(12):1081–7.
Krall J, Gabbay R, Zickmund S, Hamm ME, Williams KR, Siminerio L. Current perspectives on psychological insulin resistance: primary care provider and patient views. Diabetes Technol Ther. 2015;17(4):268–74.
Chatterjee S, Davies MJ, Heller S, Speight J, Snoek FJ, Khunti K. Diabetes structured self-management education programmes: a narrative review and current innovations. Lancet Diabetes Endocrinol. 2018;6(2):130–42.
Peyrot M, Barnett AH, Meneghini LF, Schumm-Draeger PM. Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabet Med. 2012;29(5):682–9.
Riddle MC, Rosenstock J, Gerich J. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003;26(11):3080–6.
Khunti K, Nikolajsen A, Thorsted BL, Andersen M, Davies MJ, Paul SK. Clinical inertia with regard to intensifying therapy in people with type 2 diabetes treated with basal insulin. Diabetes Obes Metab. 2016;18(4):401–9.
Yki-Jarvinen H, Bergenstal RM, Bolli GB, et al. Glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus insulin glargine 100 U/ml in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: the EDITION 2 randomized 12-month trial including 6-month extension. Diabetes Obes Metabol. 2015;17(12):1142–9.
Weatherall J, Polonsky WH, Lanar S, et al. When insulin degludec enhances quality of life in patients with type 2 diabetes: a qualitative investigation. Health Qual Life Outcomes. 2018;16(1):87.
Heise T, Mathieu C. Impact of the mode of protraction of basal insulin therapies on their pharmacokinetic and pharmacodynamic properties and resulting clinical outcomes. Diabetes Obes Metab. 2017;19(1):3–12.
Becker RH, Dahmen R, Bergmann K, Lehmann A, Jax T, Heise T. New insulin glargine 300 Units. mL−1 provides a more even activity profile and prolonged glycemic control at steady state compared with insulin glargine 100 Units. mL−1. Diabetes Care. 2015;38(4):637–43.
Heise T, Hovelmann U, Nosek L, Hermanski L, Bottcher SG, Haahr H. Comparison of the pharmacokinetic and pharmacodynamic profiles of insulin degludec and insulin glargine. Expert Opin Drug Metab Toxicol. 2015;11(8):1193–201.
Meneghini L, Atkin SL, Gough SC, et al. The efficacy and safety of insulin degludec given in variable once-daily dosing intervals compared with insulin glargine and insulin degludec dosed at the same time daily: a 26-week, randomized, open-label, parallel-group, treat-to-target trial in individuals with type 2 diabetes. Diabetes Care. 2013;36(4):858–64.
Farmer AJ, Oke J, Stevens R, Holman RR. Differences in insulin treatment satisfaction following randomized addition of biphasic, prandial or basal insulin to oral therapy in type 2 diabetes. Diabetes Obes Metabol. 2011;12(12):1136–41.
Sanofi. Toujeo SMPC. 03/2018. http://products.sanofi.us/toujeo/toujeo.pdf. Accessed 25 Sept 2018.
Ritzel R, Roussel R, Giaccari A, Vora J, Brulle-Wohlhueter C, Yki-Jarvinen H. Better glycaemic control and less hypoglycaemia with insulin glargine 300 U/mL vs glargine 100 U/mL: 1-year patientlevel meta-analysis of the EDITION clinical studies in people with type 2 diabetes. Diabetes Obes Metab. 2018;20(3):541–8.
NovoNordisk. Tresiba SmPC. https://www.novo-pi.com/tresiba.pdf. Accessed 25 Sept 2018.
Bilal A, Pratley RE. Cardiovascular outcomes trials update: insights from the DEVOTE trial. Curr Diab Rep. 2018;18(11):102.
NHS Digital. National Diabetes Inpatient Audit (NaDIA), 2017.
Evans M, Mehta R, Gundgaard J, Chubb B. Cost-Effectiveness of insulin degludec vs. insulin glargine U100 in type 1 and type 2 diabetes mellitus in a UK setting. Diabetes Ther. 2018;9(5):1919–30.
Pollock RF, Valentine WJ, Marso SP, et al. DEVOTE 5: evaluating the short-term cost-utility of insulin degludec versus insulin glargine U100 in basal-bolus regimens for Type 2 diabetes in the UK. Diabetes Ther. 2018;9(3):1217–32.
Gough SC, Bode B, Woo V, et al. Efficacy and safety of a combination of insulin degludec and liraglutide (IDegLira) in patients with Type 2 diabetes after 1 year of treatment. Diabetic medicine. 2015;2(11):885–93.
The authors acknowledge support from the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care—East Midlands (NIHR CLAHRC—EM), the Leicester Clinical Trials Unit and the NIHR Leicester Biomedical Research Centre, which is a partnership between University Hospitals of Leicester NHS Trust, Loughborough University and the University of Leicester. No sources of funding were used to assist in the preparation of this article.
Conflict of Interest
SC has received speaker fees or educational funding, or both, from Janssen, Eli Lilly, Novo Nordisk, AstraZeneca, and Boehringer Ingelheim and grants in support of investigator initiated trials from Boehringer Ingelheim and Janssen. KK has acted as a consultant and speaker for AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Janssen, and Boehringer Ingelheim, has received grants in support of investigator and investigator-initiated trials from AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, Merck Sharp & Dohme, and Roche, and has served on advisory boards for AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Janssen, and Boehringher Ingelheim. MJD reports personal fees from Novo Nordisk, Sanofi-Aventis, Eli Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca, Janssen, Mitsubishi Tanabe Pharma Corporation, and Takeda Pharmaceuticals International and grants from Novo Nordisk, Sanofi- Aventis, Eli Lilly, Boehringer Ingelheim, and Janssen.
The original version of this article was revised: Due to Section 4.1 third paragraph update.
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Chatterjee, S., Khunti, K. & Davies, M.J. Achieving Glycaemic Control with Concentrated Insulin in Patients with Type 2 Diabetes. Drugs 79, 173–186 (2019). https://doi.org/10.1007/s40265-018-1048-6