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This review examines the new formulation of insulin glargine (recombinant) in the form of injections 300 U/ml (Gla‑300, Toujeo®). Gla‑300 is a next generation basal insulin with a novel formulation of insulin glargin delivering the same amount of insulin, as Gla‑100 (Lantus®), in 1/3 of the volume. Following the subcutaneous injection, the pharmacokinetic and pharmacodynamic profiles of Gla‑300 are more stable and prolonged (beyond 24 hours) compared with Gla‑100, due to a more gradual and extended release of glargine from the subcutaneous depot (Gla‑300 forms a more compact subcutaneous depot with a smaller surface compared to Gla‑100). The clinical efficacy and safety of Gla‑300 in people with type 1 and type 2 diabetes mellitus are discussed with an emphasis on recently released data from the EDITION (phase 3a) clinical trials. Gla‑300 demonstrates comparable glycaemic control and similar safety profile with lower incidence of hypoglycaemia events (first of all, nocturnal hypoglycemia) compared to Gla‑100. Gla‑300 provided a flexible regimen of insulin administration (24 ± 3 h in the morning vs in the evening) and was associated with less body weight gain.
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Ahsen B. Avoiding hypoglycemia: a key to success for glucose-lowering therapy in type 2 diabetes. Vasc Healht Risk Man 2013;9:155-163 doi: 10.2147/VHRM.S33934.
American Diabetes Association Workgroup On Hypoglycemia. Defining and Reporting Hypoglycemia in Diabetes. Diabetes Care 2005;28(5):1245-1249. doi:10.2337/diacare.28.5.1245.
Atkinson MA, Herrath M., Powers AC, Clare-Salzer M. Current concepts of the pathogenesis of type 1 diabetes - considerations for attempts to prevent and reverse the disease. Diabetes Care 2015;38:979-988 doi 10.2337/dc15-0144.
Becker RH, Frick AD, Teichert L. Nosek L, Heinemann L, Heise T, Rave K. Fluctuation and reproducibility of exposure and effect of insulin glargine in healthy subjects. Diabetes Obes Metab 2008;10(11):1105-1113 doi: 10.1111/j.1463-1326.2008.00874.x.
Becker RHA, Nowotny I, Teichert L, Bergmann K, Kapitza C. Low within- and between-day variability in exposure to new insulin glarginc 300 U.ml-1. 74th Scientific sessions of ADA, San Francisco, USA, 13-17 June 2014, Abstract 892-P doi: 10.1111/dom.12416.
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;38:637-643. doi: 10.2337/dc14-0006.
Becker R.H.А. et al. Poster presentation at EASD 2014; Abstract 953. - [Electronic resourse]. - Available at : http://www.easdvirtualmeeting.org/resources/18262 Accessed September 2014.
Bergenstal R, Bailey T, Robard D, Guo H, Muehlen-Bartmer I, Ahmann AJ. Insulin glargine 300 U/ml vs 100 U/ml: glucose profiles of morning vs evening injections in adults with T1DM measured with continuous glucose monitoring (CGM). Diabetes Technol Ther 2015;17:A16-17. doi: 10.1089/dia.2010.0251.
Blair HA, Keating GM. Insulin Glargine 300 U/mL: A Review in Diabetes Mellitus. Drugs 2016;76(3):363-374. doi: 10.1007/s40265-016-0541-z.
Bolli GB, Riddle MC, Bergenstal RM, Ziemen M, Sestakauskas K, Goyeau H, Home PD; on behalf of the EDITION 3 study investigators. New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin-naive people with type 2 diabetes on oral glucose-lowering drugs: a randomized controlled trial (EDITION 3). Diabetes Obes Metab 2015;17:386-394. doi: 10.1111/dom.12438.
Bolli GB, De Vries JH. New long-acting insulin analogs: from clamp studies to clinical practice. Diabetes Care 2015;38:541-543. doi: 10.2337/dc14-2314.
European Medicines Agency. Toujeo (insulin glargine U300): summary of product characteristics. 2015. - Available at : http://www.ema.europa.eu/.
Garber AJ, King AB, Del Prato S, Sreenan S, Balci MK, Muñoz-Torres M, Rosenstock J, Endahl LA, Francisco AM, Hollander P; NN1250-3582 (BEGIN BB T2D) Trial Investigators. Insulin Degludec an ultra-longating basal insulin, versus insulin glargine in basal bolus treatment with mealtime insulin apart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomized open-label, treat-to-target non-inferiority trial Lancet. 2012;379: 1498-507. doi:10.1016/S0140-6736(12)60205-0.
Hirsch IB, Bergenstal RM, Parkin ChG, Wright E, Buse JB. A real-world approach to insulin therapy in primary care practice. Clin Diabet 2005;23:78-86.
Home PD, Bergenstal RM, Riddle MC, Ziemen M, Rojeski M, Espinasse M, Bolli GB. Glycemic control and hypoglycemia with new insulin glargine 300U/ml in people with T1DM (EDITION 4). 74th Scientific sessions of ADA, San Francisco, USA, 13-17 June 2014, Abstract 80-LB.
Home PD, Bergenstal RM, Bolli GB, Ziemen M, Rojeski M., Espinasse M, Riddle MC. New insulin glargine 300Units/ml versus glargine 100 Units/mL in people with type 1 diabetes: a randomized, phase 3a, open-label clinical trial (EDITION 4). Diabetes Care 2015. doi:10.2337/dc15-0249/-/DC1.
International Diabetes Federation. Diabetes Atlas, 7th edition, Brussels, Belgium: International Diabetes Federation, 2015, 143 р. - Available at : http://www.idf.org.
Jeandidier N, Riddle MC, Bolli GB, Bergenstal RM, Ziemen M, Muehlen-Bartner I, Wardecki M, Vinet L, Yki-Jarvinen H. New insulin Glargine 300 U/ml: efficacy and safety of flexible vs fixed dosing intervals in people with 2 diabetes mellitus. 50th Annual meeting of the European Association for the Study Diabetes, Vienna, Austria, 15-19 September 2014, Abstract 961.
Jinnouchi H, Koyama M, Amano A, Takahashi Y, Yoshida A, Hieshima K, Sugiyama S, Krinami N, Jinnouchi T, Becker R. Continuous Glucose monitoring during basal-bolus therapy using Glargine 300 U ml-1 and Glargine 100 U ml-1 in Japanese People with Type 1 Diabetes Mellitus: A Crossover pilot study. Diabetes Ther 2015. doi 10.1007/s13300-015-0115-1.
Martens GA, Van de Casteele M. Glycemic control of apoptosis in the pancreatic beta cell: danger of extremes? Antioxid Redox Sygnal 2007;9:309-317. PMID: 17184175
Matsuhisa M, Koyama M, Cheng X, Shimizu S, Hirose T. EDITION JP 1 Study Group. New insulin glargine 300 U/mL: glycemic control and hypoglycemia in Japanese people with T1DM (EDIT1C JP I). 74th Scientific sessions of ADA, San Francisco, USA, 13-17 June 2014, Abstract 88-LB.
Monami M, Adalsteinsson JE, Desireri CM, Ragghianti B, Dicembrini I, Mannucci E. Fasting and post-prandial glucose and diabetic complication. A meta-analysis. Nurt Metab Cardiovasc Dis 2013;23:591-598. doi: 10.1016/j.numecd.2013.03.007.
Monnier L, Colette C, Owens D. The glycemic triumvirate and diabetic complicatyions: Is the whole greater than the sum of its component parts? Diabetes Res Clin Pract. 2012;95:303-311. doi:10.1016/j/diabres.2011.10.014.
Monnier L, Owens DR, Bolli GB. The new insulin glargine U300 achieves an early steady state with low risk of accumulation. Diabetes Metab. 2015. - Available at : http://dx.doi.org/10.1016/j.diabet.2015.11.005.
Nolan CJ, Damm P, Prentki M. Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet 2011;378:169-181. doi: 10.1016/S0140-6736(11)60614-4.
Ricci C, Pastukh V, Mozafarri M, Shaffer SW. Insulin withdrawal induces apoptosis via a free radical mediated mechanism. Can J Physiol Pharmacol 2007;85:455-464. doi:10.1139/Y07-02.
Riddle MC, Bolli GB, Ziemen M, Muehlen-Bartmer I, Bizet F, Home PD; EDITION 1 Study Investigators. 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;37:2755-2762. doi:10.2337/dc14-0991.
Riddle MC, Bolli GB, Yki-Jarvinen H, Ziemen M, Muehlen-Bartmer I, Cissokho S, Home PD. Sustained glycemic control and hypoglycemia with new insulin glargine 300 U/mL compared with 100 U/ml: one-year results in people with T2DM using basal + mealtime insulin (EDITION 1). 74th Scientific sessions of ADA, San Francisco, USA, 13-17 June 2014, Abstract 81-LB.
Riddle MC, Home PD, Avogaro A. et al. A clinically-defined nocturnal window for analysis of hypoglycemia with new insulin glargine 300 U/mL in type 2 diabetes (T2DM). Diabetes 2015;64(Suppl 1):A263.
Ritzel R, Roussel R, Bolli GB, Vinet L, Brulle-Wohlhueter C, Glezer S, Yki-Jarvinen H. 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;9:859-867. doi: 10.1111/dom.12485.
Ritzel R, Roussel R, Giaccari A, Vora JP, Grisoni M-L, Brulle-Wohlhueter C, Glezer S, Yki-Jarvinen H.. Glycemic control and hypoglycemia with insulin glargine 300 U/mL (Gla-300) vs glargine 100 U/mL (Gla-100) in type 2 diabetes (T2DM) in a patient-level meta-analysis of 1-year phase 3a EDITION studies. 75th Scientific sessions of ADA, Boston, USA, 5-9 June 2015, Abstract 1030-P.
Rosenstock J, Zhang Q, Gerrits C. et al. Is hypoglycemia a modifiable patient risk in type 2 diabetes? A pooled analysis of insulin glargine 300U/ml (Gla-300) vs. 100U/ml (Gla-100) trials. Diabetes 2015;64(Suppl.):A110.
Steinstraesser A, Schmidt R, Bergmann K, Dahmen R, Becker RHA. Investigational new insulin glargine 300 U/ml has the same metabolism as insulin glargine 100 U/ml. Diabetes Obes Metab 2014;16:873-876. doi:10.1111/dom.12283.
Sutton G, Minguet J, Ferrero C, Bramlage P. U300, A novel long-acting insulin formulation. Expert Opin Biol Ther 2014;14:1849-1860. doi: 10.1517/14712598.2014.970633.
Terauchi Y, Koyama M, Cheng X, Shimizu S, Hirose T, on behalf of the EDITION JP 2 study group. Glycemic control and hypoglycaemia in Japanese people with T2DM receiving New insulin Glargine 300 U/ml in combination with OADs (EDITION JP 2). 50th Annual meeting of the European Association for the Study Diabetes, Vienna, Austria, 15-19 September 2014, Abstract 976.
Tschope D, Bramlage P, Binz C, Krekler M, Deeg E, Gitt A. Incidence and predictors of hypoglycaemia in type 2 diabetes – an analysis of the prospective DiaRegis registry. BMC Endocr Disord 2012;12:23. doi: 10.1186/1472-6823-12-23.
Twigg SM, Escalada J, Grisoni M-L, Stella P, Merino-Trigo A, Lavalle-Gonzalez FJ, Cariou B, Meneghini F. Age, BMI, and diabetes duration: effect on glycemic control and hypoglycemia with insulin glargine 300 U/mL in type 2 diabetes (T2DM). 75th Scientific sessions of ADA, Boston, USA, 5-9 June 2015, Abstract 1017-P.
Xie L, Wei W, Pan C, Baser O. Real-world rates, predictors and associated costs of hypoglycemia among patients with type 2 diabetes mellitus treated with insulin glargine: results of a pooled analysis of six retrospective observational studies. J Med Econ 2013;16:1137-1145. doi: 10.3111/13696998.2013.824458
Yakubovich N, Gerstein HC. Serious cardiovascular outcomes in diabetes: the role of hypoglycemia. Circulation 2011;123:342-348. doi: 10.1161/CIRCULATIONAHA.110.948489.
Yki-Jarvinen H, Bergenstal R, Ziemen M, Wardecki M, Muehlen-Bartmer I, Boelle E, Riddle MC, EDITION 2 Study Investigators. New insulin glargine 300 U/mL versus glargine 100 U/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;37:3235-3243. doi:10.2337/dc14-0990.
Yki-Jarvinen H, Bergenstal RM, Bolli GB, Ziemen M, Wardecki M, Muehlen-Bartmer I, Maroccia M. Less nocturnal hypoglycemia and weight gain with new insulin glargine 300 U/ml compared with 100 U/ml: 1-year results in people with T2DM using basal insulin with OADs (EDITION 2). 74th Scientific sessions of ADA, San Francisco, USA, 13-17 June 2014, Abstract 93-LB.
Efimov AS, Poltorak VV. Autoimmunnyie aspektyi insulinzavisimogo saharnogo diabeta. Popyitki immunokorrektsii na rannih stadiyah zabolevaniya. Probl endokrinol 1989;35:85-90.
Compendium — lekarstvennye preparaty. 2015. Available at : http://compendium.com.ua/info/252094/sanofi/tozheo-solostar.
Preparat Tozheo® (Toujeo®) zatverdzhenyy u Yevropeys'komu soyuzi dlya likuvannya diabetu u doroslykh – novyy bazal'nyy insulin pokazav hlikemichnyy kontrol' iz menshoyu kil'kistyu vypadkiv pidtverdzhenoyi hipohlikemiyi. Mizhnarodnyy endokrynolohichnyy zhurnal 2015; 67:96-98.
Poltorak VV, Krasova NS, Gorshunska MY. Glykemycheskaya pamyat' kak patohenetycheskoe osnovanye dlya formyrovanyya alhorytma sovremennoy antydyabetycheskoy terapyy. Mizhnarodnyy endokrynolohichnyy zhurnal 2014;(3):15-21.
Poltorak VV, Krasova NS, Gorshunskaia MY. Apoptoz pankreaticheskih beta-kletok kak novaya mishen dlya insulinoterapii bolnyih saharnyim diabetom 1 i 2 tipa. Problemyi endokrinnoy patologii 2015;1:90-102.