Concepts and clinical use of ultra-long basal insulin

Diabetology & Metabolic Syndrome

Tânia Barreto¹  Freddy Goldberg Eliaschewitz² 

[1] Sanofi´s Medical Division, América Business Park-5200, Major Sylvio de Magalhães Padilha Av., Jd. Morumbi, São Paulo 05693-000, SP, Brazil;CPClin Clinical Research Center, 91, Goiás St., São Paulo 01244-030, SP, Brazil

关键词: Hypoglycemia;    Glycemic control;    Ultra-long basal insulin;    Diabetes mellitus;   

Others  :  1235249
DOI  :  10.1186/s13098-015-0117-1

【 摘 要 】

Diabetes mellitus (DM) is a public health issue, affecting around 382 million people worldwide. In order to achieve glycemic goals, insulin therapy is the frontline therapy for type 1 DM patients; for patients with type 2 DM, use of insulin therapy is an option as initial or add-on therapy for those not achieving glycemic control. Despite insulin therapy developments seen in the last decades, several barriers remain for insulin initiation and optimal maintenance in clinical practice. Fear of hypoglycemia, weight gain, pain associated with blood testing and injection-related pain are the most cited reasons for not starting insulin therapy. However, new generation of basal insulin formulations, with longer length of action, have shown the capability of providing adequate glycemic control with lower risk of hypoglycemia.

【 授权许可】

   
2016 Eliaschewitz and Barreto.

【 图 表 】

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【 参考文献 】

• [1]International Diabetes Federation IDF: IDF Diabetes Atlas—6th edition. 6th edition. IDF, Brussels; 2013.
• [2]American Diabetes Association: Standards of medical care in diabetes—2014 Diabetes Care 2014, 37(Suppl 1):S14-S80.
• [3]The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus N Engl J Med 1993, 329(14):977-986.
• [4]Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):837–53.
• [5]Fullerton B, Jeitler K, Seitz M, Horvath K, Berghold A, Siebenhofer A: Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus. Cochrane Database Syst Rev. 2014, 2:CD009122.
• [6]Hemmingsen B, Lund SS, Gluud C, Vaag A, Almdal TP, Hemmingsen C, et al.: Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2013, 11:CD008143.
• [7]Kramer CK, Zinman B, Retnakaran R: Are metabolically healthy overweight and obesity benign conditions?: A systematic review and meta-analysis. Ann Intern Med 2013, 159(11):758-769.
• [8]Rosenfeld L: Insulin: discovery and controversy. Clin Chem 2002, 48(12):2270-2288.
• [9]Hirsch IB: Insulin analogues. N Engl J Med 2005, 352(2):174-183.
• [10]Owens DR, Matfin G, Monnier L: Basal insulin analogues in the management of diabetes mellitus: What progress have we made? Diabetes Metab Res Rev. 2014, 30(2):104-119.
• [11]Swinnen SG, Simon AC, Holleman F, Hoekstra JB, Devries JH: Insulin detemir versus insulin glargine for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2011, 7:CD006383.
• [12]Horvath K, Jeitler K, Berghold A, Ebrahim SH, Gratzer TW, Plank J, et al.: Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007, 2:CD005613.
• [13]Unger J: Uncovering undetected hypoglycemic events. Diabetes Metab Syndr Obes. 2012, 5:57-74.
• [14]Arnolds S, Kuglin B, Kapitza C, Heise T: How pharmacokinetic and pharmacodynamic principles pave the way for optimal basal insulin therapy in type 2 diabetes. Int J Clin Pract 2010, 64(10):1415-1424.
• [15]Heinemann L, Chantelau EA, Starke AA: Pharmacokinetics and pharmacodynamics of subcutaneously administered U40 and U100 formulations of regular human insulin. Diabete Metab 1992, 18(1):21-24.
• [16]Heinemann L: Time-action profiles of insulin preparations. Verlag Kirchheim + Co., GmbH, Mainz; 2004.
• [17]Lepore M, Pampanelli S, Fanelli C, Porcellati F, Bartocci L, Di Vincenzo A, et al.: Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes 2000, 49(12):2142-2148.
• [18]Owens DR, Coates PA, Luzio SD, Tinbergen JP, Kurzhals R: Pharmacokinetics of 125I-labeled insulin glargine (HOE 901) in healthy men: comparison with NPH insulin and the influence of different subcutaneous injection sites. Diabetes Care 2000, 23(6):813-819.
• [19]Abe S, Inoue G, Yamada S, Irie J, Nojima H, Tsuyusaki K, et al.: Two-way crossover comparison of insulin glargine and insulin detemir in basal-bolus therapy using continuous glucose monitoring. Diabetes Metab Syndr Obes. 2011, 4:283-288.
• [20]Heise T, Pieber TR: Towards peakless, reproducible and long-acting insulins. An assessment of the basal analogues based on isoglycaemic clamp studies. Diabetes Obes Metab 2007, 9(5):648-659.
• [21]Ashwell SG, Gebbie J, Home PD: Twice-daily compared with once-daily insulin glargine in people with Type 1 diabetes using meal-time insulin aspart. Diabet Med 2006, 23(8):879-886.
• [22]Ratner RE, Gough SC, Mathieu C, Del Prato S, Bode B, Mersebach H, 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):175-184.
• [23]Heller S, Buse J, Fisher M, Garg S, Marre M, Merker L, et al.: Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet 2012, 379(9825):1489-1497.
• [24]Bergenstal RM, Rosenstock J, Arakaki RF, Prince MJ, Qu Y, Sinha VP, et al.: 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, 35(11):2140-2147.
• [25]Rosenstock J, Bergenstal RM, Blevins TC, Morrow LA, Prince MJ, Qu Y, et al.: Better glycemic control and weight loss with the novel long-acting basal insulin LY2605541 compared with insulin glargine in type 1 diabetes: a randomized, crossover study. Diabetes Care 2013, 36(3):522-528.
• [26]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):637-643.
• [27]Tillner J, Bergmann K, Teichert L, Dahmen R, Heise T, Becker RHA. Euglycemic clamp profile of new insulin glargine U300 formulation in patients with type 1 diabetes (T1DM) is different from glargine U100 (Abstract). Diabetes 2013. p. A920-P.
• [28]Riddle MC, Bolli GB, Ziemen M, Muehlen-Bartmer I, Bizet F, Home PD: 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):2755-2762.
• [29]Yki-Jarvinen H, Bergenstal R, Ziemen M, Wardecki M, Muehlen-Bartmer I, Boelle E, 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):3235-3243.
• [30]Bode BW, Buse JB, Fisher M, Garg SK, Marre M, Merker L, et al.: Insulin degludec improves glycaemic control with lower nocturnal hypoglycaemia risk than insulin glargine in basal-bolus treatment with mealtime insulin aspart in Type 1 diabetes (BEGIN((R)) Basal-Bolus Type 1): 2-year results of a randomized clinical trial. Diabet Med 2013, 30(11):1293-1297.
• [31]Mathieu C, Hollander P, Miranda-Palma B, Cooper J, Franek E, Russell-Jones D, et al.: Efficacy and safety of insulin degludec in a flexible dosing regimen vs insulin glargine in patients with type 1 diabetes (BEGIN: Flex T1): a 26-week randomized, treat-to-target trial with a 26-week extension. J Clin Endocrinol Metab 2013, 98(3):1154-1162.
• [32]Garber AJ, King AB, Del Prato S, Sreenan S, Balci MK, Munoz-Torres M, 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):1498-1507.
• [33]Hollander P, King AB, Del Prato S, Sreenan S, Balci MK, Munoz-Torres M, et al.: Insulin degludec improves long-term glycaemic control similarly to insulin glargine but with fewer hypoglycaemic episodes in patients with advanced type 2 diabetes on basal-bolus insulin therapy. Diabetes Obes Metab 2014.
• [34]Zinman B, Philis-Tsimikas A, Cariou B, Handelsman Y, Rodbard HW, Johansen T, 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):2464-2471.
• [35]Rodbard HW, Cariou B, Zinman B, Handelsman Y, Philis-Tsimikas A, Skjoth TV, et al.: Comparison of insulin degludec with insulin glargine in insulin-naive subjects with Type 2 diabetes: a 2-year randomized, treat-to-target trial. Diabet Med 2013, 30(11):1298-1304.
• [36]Meneghini L, Atkin SL, Gough SC, Raz I, Blonde L, Shestakova M, 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):858-864.
• [37]Home PD, Bergenstal RM, Bolli GB, Ziemen M, Rojeski M, Espinasse M, et al.: New Insulin Glargine 300 Units/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.
• [38]Riddle MC, Yki-Järvinen H, Bolli GB, Ziemen M, Muehlen-Bartmer I, Cissokho S et al. Sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/ml vs 100 U/ml: 1-year results in type 2 diabetes with basal and mealtime insulin (EDITION 1). 50th European Association for the Study of Diabetes annual meeting; Vienna 2014.
• [39]Yki-Järvinen H, Bergenstal RM, Bolli GB, Ziemen M, Wardecki M, Muehlen-Bartmer I et al. Less nocturnal hypoglycaemia and weight gain with new insulin glargine 300 U/ml vs 100 U/ml: 1-year results in people with type 2 diabetes using basal insulin and OADs (EDITION 2). 50th European Association for the Study of Diabetes annual meeting; Vienna 2014.
• [40]Bolli GB, Riddle MC, Bergenstal RM, Ziemen M, Sestakauskas K, Goyeau H, et al.: 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.
• [41]Jeandidier N, Riddle MC, Bolli GB, Home PD, Bergenstal RM, Ziemen M et al. New insulin glargine 300 U/ml: efficacy and safety of flexible vs fixed dosing intervals in people with type 2 diabetes mellitus. 50th European Association for the Study of Diabetes annual meeting; Vienna 2014.
• [42]Lau AN, Tang T, Halapy H, Thorpe K, Yu CH: Initiating insulin in patients with type 2 diabetes. CMAJ 2012, 184(7):767-776.
• [43]Sorli C, Heile MK: Identifying and meeting the challenges of insulin therapy in type 2 diabetes. J Multidiscip Healthc. 2014, 7:267-282.
• [44]Davies MJ, Gagliardino JJ, Gray LJ, Khunti K, Mohan V, Hughes R: Real-world factors affecting adherence to insulin therapy in patients with Type 1 or Type 2 diabetes mellitus: a systematic review. Diabet Med 2013, 30(5):512-524.
• [45]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):682-689.
• [46]Donnelly LA, Morris AD, Frier BM, Ellis JD, Donnan PT, Durrant R, et al.: Frequency and predictors of hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes: a population-based study. Diabet Med 2005, 22(6):749-755.
• [47]Risk of hypoglycaemia in types: 1 and 2 diabetes: effects of treatment modalities and their duration Diabetologia 2007, 50(6):1140-1147.
• [48]Brunton SA: Nocturnal hypoglycemia: answering the challenge with long-acting insulin analogs. MedGenMed. 2007, 9(2):38.
• [49]The DCCT Research Group: Epidemiology of severe hypoglycemia in the diabetes control and complications trial Am J Med 1991, 90(4):450-459.
• [50]Lopez JM, Annunziata K, Bailey RA, Rupnow MF, Morisky DE: Impact of hypoglycemia on patients with type 2 diabetes mellitus and their quality of life, work productivity, and medication adherence. Patient Prefer Adherence. 2014, 8:683-692.
• [51]Brod M, Christensen T, Thomsen TL, Bushnell DM: The impact of non-severe hypoglycemic events on work productivity and diabetes management. Value Health. 2011, 14(5):665-671.
• [52]Levy AR, Christensen TL, Johnson JA: Utility values for symptomatic non-severe hypoglycaemia elicited from persons with and without diabetes in Canada and the United Kingdom. Health Qual Life Outcomes. 2008, 6:73. BioMed Central Full Text
• [53]Williams SA, Shi L, Brenneman SK, Johnson JC, Wegner JC, Fonseca V: The burden of hypoglycemia on healthcare utilization, costs, and quality of life among type 2 diabetes mellitus patients. J Diabetes Complications 2012, 26(5):399-406.
• [54]UK Prospective Diabetes Study (UKPDS) Group: Quality of life in type 2 diabetic patients is affected by complications but not by intensive policies to improve blood glucose or blood pressure control (UKPDS 37) Diabetes Care 1999, 22(7):1125-1136.
• [55]Brod M, Wolden M, Christensen T, Bushnell DM: A nine country study of the burden of non-severe nocturnal hypoglycaemic events on diabetes management and daily function. Diabetes Obes Metab 2013, 15(6):546-557.
• [56]Evans M, Khunti K, Mamdani M, Galbo-Jorgensen CB, Gundgaard J, Bogelund M, et al.: Health-related quality of life associated with daytime and nocturnal hypoglycaemic events: a time trade-off survey in five countries. Health Qual Life Outcomes. 2013, 11:90. BioMed Central Full Text
• [57]Edelman SV, Blose JS: The Impact of Nocturnal Hypoglycemia on Clinical and Cost-Related Issues in Patients With Type 1 and Type 2 Diabetes. Diabetes Educ. 2014, 40(3):269-279.
• [58]Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV: Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 2009, 301(15):1565-1572.
• [59]Tibaldi JM: Evolution of insulin development: focus on key parameters. Adv Ther 2012, 29(7):590-619.