Insulin degludec: Reduktion von Hypoglykämien unter einer Basis-Bolus Therapie bei Patienten mit Diabetes mellitus Typ 1 oder 2

Zusammenfassung

Insulin degludec (IDeg) ist ein neues lang wirksames Basalinsulin. Aufgrund des stabilen, flachen Wirkprofils von IDeg kommt es zu einer gleichmäßigen Verteilung des blutzuckersenkenden Effekts über 24 h, wobei die Wirkung über 24 h hinausgeht. Für IDeg wurde ein umfassendes Phase-3-Studienprogramm, in dem mehr als 4200 Patienten mit Typ-1-Diabetes und Typ-2-Diabetes in unterschiedlichen Erkrankungsstadien mit IDeg behandelt wurden, durchgeführt. Zur Basis-Bolus-Therapie mit IDeg liegen 2 Phase-3-Studien vor, die im Vergleich zu Insulin glargin ein signifikant geringeres Risiko für nächtliche Hypoglykämien bei Patienten mit Typ-1- bzw. Typ-2-Diabetes zeigen. Außerdem wurde die Rate der Gesamthypoglykämien bei der Therapie des Typ-2-Diabetes mit IDeg signifikant reduziert. IDeg stellt einen Fortschritt im Bereich der Diabetes-Therapie dar, da im Vergleich zu Insulin glargin bei mindestens gleich guter Effektivität (HbA_1c-Reduktion) weniger Hypoglykämien (insbesondere nächtliche) auftraten.

Abstract

Insulin degludec (IDeg) is a new long acting basal insulin. Due to the stable, flat action profile of IDeg there is a consistent distribution of the blood glucose lowering effect over 24 hours and the effect exceeds 24 hours. In a comprehensive phase 3 study program more than 4200 type 1 und type 2 diabetic patients in various disease stages were treated with IDeg. Regarding basis-bolus treatment there are two phase 3 studies showing a significantly lower risk for nocturnal hypoglycemia compared with Insulin glargin in patients with type 1 diabetes and type 2 diabetes respectively. In addition, the rate for overall hypoglycemia was significantly reduced during treatment of type 2 diabetes. IDeg represents a progress in the field of diabetes treatment because less hypoglycemia (especially nocturnal) occurred while efficacy of Ideg (HbA_1c reduction) is at least equal to efficacy of Insulin glargin.

Schlüsselwörter

Diabetes - Basalinsulin - Insulin degludec - Hypoglykämien - Basis-Bolus

Key words

Diabetes - basal insulin - insulin degludec - hypoglycemia - basal-bolus

• Literatur

• 1 Johnston SS, Conner C, Aagren M et al. Evidence linking hypoglycemic events to an increased risk of acute cardiovascular events in patients with type 2 diabetes. Diabetes Care 2011; 34: 1164-1170
• 2 Whitmer RA, Karter AJ, Yaffe K et al. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 2009; 301: 1565-1572
• 3 Johnston SS, Conner C, Aagren M et al. Association between hypoglycemic events and fall-related fractures in Medicare-covered patients with type 2 diabetes. Diabetes Obes Metab 2012;
• 4 Allen KV, Frier BM. Nocturnal hypoglycemia: clinical manifestations and therapeutic strategies toward prevention. Endocr Pract 2003; 9: 530-543
• 5 Brod M, Christensen T, Thomsen TL et al. The impact of non-severe hypogylcemic events on work productivity and diabetes management. Value in Health 2011; 14: 665-671
• 6 Heinemann L, Linkeschova R, Rave K et al. Time-action profile of the long-acting insulin analog insulin glargine (HOE901) in comparison with those of NPH insulin and placebo. Diabetes Care 2000; 23: 644-649
• 7 Plank J, Bodenlenz M, Sinner F et al. A double-blind, randomized, dose-response study investigating the pharmacodynamic and pharmacokinetic properties of the long-acting insulin analog detemir. Diabetes Care 2005; 28: 1107-1112
• 8 Kolendorf K, Ross GP, Pavlic-Renart I et al. Insulin detemir lowers the risk of hypoglycaemia and provides more consistent plasma glucose levels compared with NPH insulin in type 1 diabetes. Diabet Med 2006; 23: 729-735
• 9 Rosenstock J, Dailey G, Massi-Benedetti M et al. Reduced hypoglycemia risk with insulin glargine: a meta-analysis comparing insulin glargine with human NPH insulin in type 2 diabetes. Diabetes Care 2005; 28: 950-955
• 10 Hermansen K, Davies M, Derezinski T et al. A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulinnaive people with type 2 diabetes. Diabetes Care 2006; 29: 1269-1274
• 11 Horvath K, Jeitler K, Berghold A et al. Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus. Cochrane Database Syst Rev 2007; 2: CD005613
• 12 Mullins P, Sharplin P, Yki-Jarvinen H et al. Negative binomial meta-regression analysis of combined glycosylated hemoglobin and hypoglycemia outcomes across eleven Phase III and IV studies of insulin glargine compared with neutral protamine Hagedorn insulin in type 1 and type 2 diabetes mellitus. Clin Ther 2007; 29: 1607-1619
• 13 Bartley PC, Bogoev M, Larsen J et al. Long-term efficacy and safety of insulin detemir compared to neutral protamine Hagedorn insulin in patients with Type 1 diabetes using a treat-to-target basal-bolus regimen with insulin aspart at meals: a 2-year, randomized, controlled trial. Diabet Med 2008; 25: 442-449
• 14 Donnelly LA, Morris AD, Frier BM et al., DARTS/MEMO Collarboration. Frequency and predictors of hypoglycaemia in type 1 and insulin-treated type 2 diabetes: a population-based study. Diabet Med 2005; 22: 749-755
• 15 Williams SA, Pollack MF, Dibonaventura M. Effects of hypoglycemia on health-related quality of life, treatment satisfaction and healthcare resource utilization in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2011; 91: 363-370
• 16 Kurtzhals P, Heise T, Strauss HM et al. Multi-hexamer formation is the underlying basis for the ultra-long glucose-lowering effect of insulin degludec. Diabetologia 2011; 54 (Suppl. 01) S426
• 17 Kurtzhals P. Engineering predictability and protraction in a basal insulin analogue: the pharmacology of insulin detemir. Int J Obes Relat Metab Disord 2004; 28 (Suppl. 02) S23-S28
• 18 Birkeland KI, Home PD, Wendisch U et al. Insulin degludec in type 1 diabetes. A randomized controlled trial of a new generation ultra-long-acting insulin compared with insulin glargine. Diabetes Care 2011; 34: 661-665
• 19 Zinman B, Fulcher G, Rao PV et al. Insulin degludec, an ultra-long-acting basal insulin, once a day or three times a week versus insulin glargine once a day in patients with type 2 diabetes: a 16-week, randomised, open-label, phase 2 trial. Lancet 2011; 377 (9769) 924-931
• 20 Heller S, Buse J, Fisher M et al., on behalf of the BEGIN Basal-Bolus Type 1 Trial Investigators. 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: 1489-1497
• 21 Garber AJ, King AB, Del Prato S et al., on behalf of the NN1250-3582 (BEGIN BB T2D) Trial Investigators. 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: 1498-1507
• 22 U. S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research (CDER). Guidance for Industry. Diabetes mellitus: developing drugs and therapeutic biologics for treatment and prevention. February 2008 http://www.fda.gov/cder/guidance/index.htm
• 23 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: 3080-3086
• 24 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: 977-986
• 25 Blonde L, Merilainen M, Karwe V et al. Patient-directed titration for achieving glycaemic goals using a once-daily basal insulin analogue: an assessment of two different fasting plasma glucose targets – the TITRATE study. Diabetes Obes Metab 2009; 11: 623-631
• 26 UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes. Effects of treatment modalities and their duration. Diabetologia 2007; 50: 1140-1147
• 27 Nakar S, Yitzhaki G, Rosenberg R et al. Transition to insulin in type 2 diabetes: family physicians’ misconception of patients’ fears contributes to existing barriers. J Diabetes Complications 2007; 21: 220-226
• 28 Cuddihy RM, Philis-Tsimikas A, Nazeri A. Type 2 diabetes care and insulin intensification: is a more multidisciplinary approach needed? Results from the MODIFY survey. Diabetes Educ 2011; 37: 111-123
• 29 Peyrot M, Barnett AH, Meneghini LF et al. Insulin adherence behaviours and barriers in the multinational global attitudes of patients and physicians in insulin therapy study. Diabet Med 2012; 29: 682-689
• 30 Brod M, Christensen T, Thomsen TL et al. The impact of non-severe hypoglycemic events on work productivity and diabetes management. Value Health 2011; 14: 665-671
• 31 Frier BM. How hypoglycaemia can affect the life of a person with diabetes. Diabetes Metab Res Rev 2008; 24: 87-92
• 32 King P, Kong MF, Parkin H et al. Well-being, cerebral function, and physical fatigue after nocturnal hypoglycemia in IDDM. Diabetes Care 1998; 21: 341-345
• 33 Veneman T, Mitrakou A, Mokan M et al. Induction of hypoglycemia unawareness by asymptomatic nocturnal hypoglycemia. Diabetes 1993; 42: 1233-1237
• 34 Gill GV, Woodward A, Casson IF et al. Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes – the “dead in bed” syndrome revisited. Diabetologia 2009; 52: 42-45
• 35 Lingvay I. Hypoglycemia in type 2 diabetes – consequences and risk assessment. US Endocrinology 2011; 7: 95-102
• 36 Amiel SA, Dixon T, Mann R et al. Hypoglycaemia in Type 2 diabetes. Diabet Med 2008; 25: 245-254
• 37 Barendse S, Singh H, Frier BM et al. The impact of hypoglycaemia on quality of life and related patient-reported outcomes in Type 2 diabetes: a narrative review. Diabet Med 2012; 29: 293-302
• 38 Breuer HW, Ptak P. Hypoglycemia – frequency, causes, induced costs. Dtsch Med Wochenschr 2012; 137: 988-992
• 39 Fidler C, Elmelund Christensen T, Gillard S. Hypoglycemia. An overview of fear of hypoglycemia, quality-of-life, and impact on costs. J Med Econ 2011; 14: 646-655
• 40 Hitchen L. Doctors are failing to tell diabetic people about UK driving rules. BMJ 2006; 332: 812
• 41 Miller DR, Fincke G, Lafrance JP et al. Hypoglycaemia and risk of myocardial infarction in US veterans with diabetes. Presented at: European Association for the Study of Diabetes (EASD) Annual Meeting, Vienna, Austria, October 1 2009
• 42 Meneghini L, Atkin SL, Bain S et al. Flexible once-daily dosing of insulin degludec does not compromise glycemic control or safety compared to insulin glargine given once daily at the same time each day in people with type 2 diabetes. Diabetes 2011; 60 (Suppl. 01) LB10-LB11
• 43 Heise T, Hövelmann U, Nosek L et al. Insulin degludec. Two-fold longer half-life and a more consistent pharmacokinetic profile than insulin glargine. Diabetologia 2011; 54 (Suppl. 01) S425
• 44 Nosek L, Heise T, Bøttcher SG et al. Ultra-long acting insulin degludec has a flat and stable glucose-lowering effect. Diabetologia 2011; 54 (Suppl. 01) S429
• 45 Heise T, Hermanski L, Nosek L et al. The pharmacodynamic variability of insulin degludec is consistently lower than insulin glargine over 24 hours at steady state. Diabetes 2011; 60 (Suppl. 01) A263
• 46 Nishimura E, Sørensen AR, Hansen BF et al. Insulin degludec: a new ultra-long, basal insulin designed to maintain full metabolic effect while minimizing mitogenic potential. Diabetologia 2010; 53 (Suppl. 01) S388-S389
• 47 Ratner R, Gough SCL, 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 2012;