Abstract
Insulin detemir (Levemir®) is a long-acting insulin analogue indicated for use as basal insulin therapy in patients with type 1 or 2 diabetes mellitus.
The protracted action of insulin detemir is explained by increased self-association and reversible binding to albumin, which slows its systemic absorption from the injection site. In glucose-clamp studies, less within-patient variability in glucose-lowering effect was seen with insulin detemir than with neutral protamine Hagedorn (NPH) insulin or insulin glargine in patients with type 1 or 2 diabetes.
The beneficial effect of insulin detemir on glycaemic control was shown in numerous randomized, open-label, multicentre trials, including when used as basal-bolus therapy in patients with type 1 or 2 diabetes and as basal therapy in addition to oral antidiabetic drugs in insulin-naive patients with type 2 diabetes. In terms of glycosylated haemoglobin (HbA1c) [primary endpoint in most trials], insulin detemir was generally at least as effective as NPH insulin, insulin glargine or insulin lispro protamine suspension in patients with type 1 or 2 diabetes, and at least as effective as biphasic insulin aspart in patients with type 2 diabetes. Less within-patient variability in blood glucose was also generally seen with insulin detemir than with NPH insulin in patients with type 1 or 2 diabetes. Significantly less weight gain was generally seen with insulin detemir than with NPH insulin in patients with type 1 diabetes or with insulin detemir than with NPH insulin, insulin glargine, insulin lispro protamine suspension or biphasic insulin aspart (in one study) in patients with type 2 diabetes (i.e. insulin detemir generally had a weight-sparing effect).
The addition of insulin detemir to liraglutide plus metformin improved glycaemic control in insulin-naive patients with type 2 diabetes and inadequate glycaemic control, although a significantly greater reduction in bodyweight was seen in patients receiving liraglutide plus metformin than in those receiving add-on therapy with insulin detemir.
Results of two trials in patients aged 2–16 or 6–17 years (and a subgroup analysis in children aged 2–5 years) indicate that a basal-bolus insulin regimen incorporating insulin detemir appears to be a suitable option for use in paediatric patients with type 1 diabetes. Less within-patient variation in self-measured fasting plasma glucose was seen with insulin detemir than with NPH insulin in one of the studies.
Insulin detemir was noninferior to NPH insulin in pregnant women with type 1 diabetes in terms of the HbA1c value achieved at 36 gestational weeks. In addition, maternal and neonatal outcomes with insulin detemir were similar to those seen with NPH insulin.
Subcutaneous insulin detemir was generally well tolerated in the treatment of patients with type 1 or 2 diabetes, including in paediatric patients and pregnant women with type 1 diabetes. The majority of adverse events, including serious adverse events, reported in insulin detemir recipients were not considered to be related to the study drug. Insulin detemir was generally associated with a significantly lower risk of nocturnal hypoglycaemia than NPH insulin in patients with type 1 or 2 diabetes, particularly nocturnal minor hypoglycaemia.
In conclusion, insulin detemir is a useful option for use as basal insulin therapy in patients with type 1 or 2 diabetes.
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References
Le Floch J-P. Critical appraisal of the safety and efficacy of insulin detemir in glycemic control and cardiovascular risk management in diabetics. Diabetes Metab Syndr Obes 2010; 3: 197–213
Skyler JS, Bergenstal R, Bonow RO, et al. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA diabetes trials. A position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association. Diabetes Care 2009 Jan; 32(1): 187–92
Kurtzhals P. Pharmacology of insulin detemir. Endocrinol Metab Clin North Am 2007 Aug; 36 Suppl. 1: 14–20
Whittingham JL, Havelund S, Jonassen I. Crystal structure of a prolonged-acting insulin with albumin-binding properties. Biochemistry 1997 Mar 11; 36(10): 2826–31
Markussen J, Havelund S, Kurtzhals P, et al. Soluble, fatty acid acylated insulins bind to albumin and show protracted action in pigs. Diabetologia 1996 Mar; 39(3): 281–8
Hamilton-Wessler M, Ader M, Dea M, et al. Mechanism of protracted metabolic effects of fatty acid acylated insulin, NN304, in dogs: retention of NN304 by albumin. Diabetologia 1999 Oct; 42(10): 1254–63
Havelund S, Plum A, Ribel U, et al. The mechanism of protraction of insulin detemir, a long-acting, acylated analog of human insulin. Pharm Res 2004 Aug; 21(8): 1498–504
Morello CM. Pharmacokinetics and pharmacodynamics of insulin analogs in special populations with type 2 diabetes mellitus. Int J Gen Med 2011; 4: 827–35
Sørensen AR, Stidsen CE, Ribel U, et al. Insulin detemir is a fully efficacious, low affinity agonist at the insulin receptor. Diabetes Obes Metab 2010 Aug; 12(8): 665–73
Kurtzhals P, Schaffer L, Sorensen A, et al. Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes 2000 Jun; 49(6): 999–1005
Werner H, Chantelau EA. Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use: compilation of reports from the past 20 years. Diabetol Metab Syndr 2011; 3(1): 13
Heinemann L, Sinha K, Weyer C, et al. Time-action profile of the soluble, fatty acid acylated, long-acting insulin analogue NN304. Diabet Med 1999 Apr; 16(4): 332–8
Brunner GA, Sendhofer G, Wutte A, et al. Pharmacokinetic and pharmacodynamic properties of long-acting insulin analogue NN304 in comparison to NPH insulin in humans. Exp Clin Endocrinol Diabetes 2000; 108(2): 100–5
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 May; 28(5): 1107–12
Porcellati F, Rossetti P, Busciantella NR, et al. Comparison of pharmacokinetics and dynamics of the long-acting insulin analogs glargine and detemir at steady state in type 1 diabetes: a double-blind, randomized, crossover study. Diabetes Care 2007 Oct; 30(10): 2447–52
Bott S, Tusek C, Jacobsen LV, et al. Insulin detemir under steady-state conditions: no accumulation and constant metabolic effect over time with twice daily administration in subjects with type 1 diabetes. Diabet Med 2006 May; 23(5): 522–8
Wutte A, Plank J, Bodenlenz M, et al. Proportional dose-response relationship and lower within-patient variability of insulin detemir and NPH insulin in subjects with type 1 diabetes mellitus. Exp Clin Endocrinol Diabetes 2007 Jul; 115(7): 461–7
Heise T, Nosek L, Ronn BB, et al. Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes. Diabetes 2004 Jun; 53(6): 1614–20
Klein O, Lynge J, Endahl L, et al. Albumin-bound basal insulin analogues (insulin detemir and NN344): comparable time-action profiles but less variability than insulin glargine in type 2 diabetes. Diabetes Obes Metab 2007 May; 9(3): 290–9
Lucidi P, Porcellati F, Rossetti P, et al. Pharmacokinetics and pharmacodynamics of therapeutic doses of basal insulins NPH, glargine, and detemir after 1 week of daily administration at bedtime in type 2 diabetic subjects: a randomized cross-over study. Diabetes Care 2011 Jun; 34(6): 1312–4
Porcellati F, Bolli GB, Fanelli CG. Pharmacokinetics and pharmacodynamics of basal insulins. Diabetes Technol Ther 2011 Jun; 13 Suppl. 1: S15–24
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 Sep; 9(5): 648–59
Hordern SV, Wright JE, Umpleby AM, et al. Comparison of the effects on glucose and lipid metabolism of equipotent doses of insulin detemir and NPH insulin with a 16-h euglycaemic clamp. Diabetologia 2005 Mar; 48(3): 420–6
Smeeton F, Shojaee Moradie F, Jones RH, et al. Differential effects of insulin detemir and neutral protamine Hagedorn (NPH) insulin on hepatic glucose production and peripheral glucose uptake during hypoglycaemia in type 1 diabetes. Diabetologia 2009 Nov; 52(11): 2317–23
Hollander PA. Insulin detemir for the treatment of obese patients with type 2 diabetes. Diabetes Metab Syndr Obes 2012; 5: 11–9
Hermansen K, Davies M. Does insulin detemir have a role in reducing risk of insulin-associated weight gain? Diabetes Obes Metab 2007 May; 9(3): 209–17
Hallschmid M, Jauch-Chara K, Korn O, et al. Euglycemic infusion of insulin detemir compared with human insulin appears to increase direct current brain potential response and reduces food intake while inducing similar systemic effects. Diabetes 2010 Apr; 59(4): 1101–7
Zachariah S, Sheldon B, Shojaee-Moradie F, et al. Insulin detemir reduces weight gain as a result of reduced food intake in patients with type 1 diabetes. Diabetes Care 2011 Jul; 34(7): 1487–91
Tschritter O, Hennige AM, Preissl H, et al. Cerebrocortical beta activity in overweight humans responds to insulin detemir. PLoS One 2007; 2(11): e1196
Garimella M, Mitchell S, Burge MR. Effects of insulin detemir versus insulin glargine on food intake and satiety factors in type 1 diabetes [abstract no. 2617-PO]. Diabetes 2011 Jul; 60 Suppl. 1: A687
Davies MJ, Derezinski T, Pedersen CB, et al. Reduced weight gain with insulin detemir compared to NPH insulin is not explained by a reduction in hypoglycemia. Diabetes Technol Ther 2008 Aug; 10(4): 273–7
Hendriksen KV, Jensen T, Oturai P, et al. Effects of insulin detemir and NPH insulin on renal handling of sodium, fluid retention and weight in type 2 diabetic patients. Diabetologia 2012 Jan; 55(1): 46–50
Tschritter O, Schäfer SA, Klett J, et al. Insulin detemir causes increased symptom awareness during hypoglycaemia compared to human insulin. Diabetes Obes Metab 2009 Nov; 11(11): 1017–26
Rossetti P, Porcellati F, Ricci NB, et al. Different brain responses to hypoglycemia induced by equipotent doses of the long-acting insulin analog detemir and human regular insulin in humans. Diabetes 2008 Mar; 57(3): 746–56
Porcellati F, Rossetti P, Candeloro P, et al. Short-term effects of the long-acting insulin analog detemir and human insulin on plasma levels of insulin-like growth factor-I and its binding proteins in humans. J Clin Endocrinol Metab 2009 Aug; 94(8): 3017–24
European Medicines Agency. Levemir (insulin detemir): EU summary of product characteristics [online]. Available from URL: http://www.emea.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000528/WC500036662.pdf [Accessed 2012 Oct 16]
Novo Nordisk Inc. Levemir® (insulin detemir [rDNA origin] injection): US prescribing information [online]. Available from URL: http://www.novo-pi.com/levemir.pdf [Accessed 2012 Oct 16]
Hompesch M, Troupin B, Heise T, et al. Time-action profile of insulin detemir and NPH insulin in patients with type 2 diabetes from different ethnic groups. Diabetes Obes Metab 2006 Sep; 8(5): 568–73
Danne T, Lüpke K, Walte K, et al. Insulin detemir is characterized by a consistent pharmacokinetic profile across age-groups in children, adolescents, and adults with type 1 diabetes. Diabetes Care 2003 Nov; 26(11): 3087–92
Kurtzhals P. Engineering predictability and protraction in a basal insulin analogue: the pharmacology of insulin detemir. Int J Obesity 2004 Sep; 28 Suppl. 2: S23–S8
Banks WA, Morley JE, Lynch JL, et al. Insulin detemir is not transported across the blood-brain barrier. Peptides 2010 Dec; 31(12): 2284–8
Danne T, Datz N, Endahl L, et al. Insulin detemir is characterized by a more reproducible pharmacokinetic profile than insulin glargine in children and adolescents with type 1 diabetes: results from a randomized, double-blind, controlled trial. Pediatr Diabetes 2008 Dec; 9(6): 554–60
Jhee SS, Lyness WH, Rojas PB, et al. Similarity of insulin detemir pharmacokinetics, safety, and tolerability profiles in healthy Caucasian and Japanese American subjects. J Clin Pharmacol 2004 Mar; 44(3): 258–64
Jacobsen LV, Popescu G, Plum A. Pharmacokinetics of insulin detemir in subjects with renal or hepatic impairment [abstract no. 806]. Diabetologia 2002 Aug; 45 Suppl. 2: A259–60
Morrow L, Hompesch M, Guthrie H, et al. Co-administration of liraglutide with insulin detemir demonstrates additive pharmacodynamic effects with no pharmacokinetic interaction. Diabetes Obes Metab 2011 Jan; 13(1): 75–80
Kurtzhals P, Havelund S, Jonassen I, et al. Effect of fatty acids and selected drugs on the albumin binding of a long-acting, acylated insulin analogue. J Pharm Sci 1997 Dec; 86(12): 1365–8
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 Apr; 25(4): 442–9
Hermansen K, Fontaine P, Kukolja KK, et al. Insulin analogues (insulin detemir and insulin aspart) versus traditional human insulins (NPH insulin and regular human insulin) in basal-bolus therapy for patients with type 1 diabetes. Diabetologia 2004 Apr; 47(4): 622–9
Home P, Bartley P, Russell-Jones D, et al. Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes: a randomized clinical trial. Diabetes Care 2004 May; 27(5): 1081–7
Pieber TR, Draeger E, Kristensen A, et al. Comparison of three multiple injection regimens for type 1 diabetes: morning plus dinner or bedtime administration of insulin detemir vs. morning plus bedtime NPH insulin. Diabet Med 2005 Jul; 22(7): 850–7
Russell-Jones D, Simpson R, Hylleberg B, et al. Effects of QD insulin detemir or neutral protamine Hagedorn on blood glucose control in patients with type I diabetes mellitus using a basal-bolus regimen. Clin Ther 2004 May; 26(5): 724–36
Vague P, Selam J-L, Skeie S, et al. Insulin detemir is associated with more predictable glycemic control and reduced risk of hypoglycemia than NPH insulin in patients with type 1 diabetes on a basal-bolus regimen with premeal insulin aspart. Diabetes Care 2003 Mar; 26(3): 590–6
Heller S, Koenen C, Bode B. Comparison of insulin detemir and insulin glargine in a basal-bolus regimen, with insulin aspart as the mealtime insulin, in patients with type 1 diabetes: a 52-week, multinational, randomized, open-label, parallel-group, treat-to-target noninferiority trial. Clin Ther 2009 Oct; 31(10): 2086–97
Pieber TR, Treichel H-C, Hompesch B, et al. Comparison of insulin detemir and insulin glargine in subjects with type 1 diabetes using intensive insulin therapy. Diabet Med 2007 Jun; 24(6): 635–42
Chacra AR, Kipnes M, Ilag LL, et al. Comparison of insulin lispro protamine suspension and insulin detemir in basal-bolus therapy in patients with type 1 diabetes. Diabet Med 2010 May; 27(5): 563–9
Le Floch J-P, Lévy M, Mosnier-Pudar H, et al. Comparison of once-versus twice-daily administration of insulin detemir, used with mealtime insulin aspart, in basal-bolus therapy for type 1 diabetes: assessment of detemir administration in a progressive treat-to-target trial (ADAPT). Diabetes Care 2009 Jan; 32(1): 32–7
Thalange NKS, Bereket A, Larsen J, et al. Comparison of insulin detemir and NPH insulin in children and adolescents (2–16 years) with T1DM: a 52-week randomized clinical trial [abstract no. 1784-P]. 69th Annual Meeting of the American Diabetes Association; 2009 Jun 5–9; New Orleans (LA)
Robertson KJ, Schoenle E, Gucev Z, et al. Insulin detemir compared with NPH insulin in children and adolescents with type 1 diabetes. Diabet Med 2007 Jan; 24(1): 27–34
Thalange N, Bereket A, Larsen J, et al. Treatment with insulin detemir or NPH insulin in children aged 2–5 yr with type 1 diabetes mellitus. Pediatr Diabetes 2011 Nov; 12(7): 632–41
Mathiesen ER, Hod M, Ivanisevic M, et al. Maternal efficacy and safety outcomes in a randomized, controlled trial comparing insulin detemir with NPH insulin in 310 pregnant women with type 1 diabetes. Diabetes Care 2012 Oct; 35(10): 2012–7
Novo Nordisk. Comparison of NPH insulin and insulin detemir in children and adolescents with type 1 diabetes [ClinicalTrials.gov identifier NCT00435019]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Oct 16]
De Leeuw I, Vague P, Selam J-L, et al. Insulin detemir used in basal-bolus therapy in people with type 1 diabetes is associated with a lower risk of nocturnal hypoglycaemia and less weight gain over 12 months in comparison to NPH insulin. Diabetes Obes Metab 2005 Jan; 7(1): 73–82
Standl E, Lang H, Roberts A. The 12-month efficacy and safety of insulin detemir and NPH insulin in basal-bolus therapy for the treatment of type 1 diabetes. Diabetes Technol Ther 2004 Oct; 6(5): 579–88
Roberts A, Standl E, Bayer T, et al. Efficacy and safety of 6-month treatment with insulin detemir in type 1 diabetic patients on a basal-bolus regimen [abstract no. 795]. Diabetologia 2001 Aug; 44 Suppl. 1: A207
Hod M, McCance DR, Ivanisevic M, et al. Perinatal outcomes in a randomized trial comparing insulin detemir with NPH insulin in 310 pregnant women with type 1 diabetes [abstract no. 62-LB]. 71st Annual Scientific Sessions of the American Diabetes Association; 2011 Jun 24–28; San Diego (CA)
Fajardo Montañana C, Hernández Herrero C, Rivas Fernández M. Less weight gain and hypoglycaemia with once-daily insulin detemir than NPH insulin in intensification of insulin therapy in overweight type 2 diabetes patients: the PREDICTIVE™ BMI clinical trial. Diabet Med 2008 Aug; 25(8): 916–23
Haak T, Tiengo A, Draeger E, et al. Lower within-subject variability of fasting blood glucose and reduced weight gain with insulin detemir compared to NPH insulin in patients with type 2 diabetes. Diabetes Obes Metab 2005 Jan; 7(1): 56–64
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 insulin-naïve people with type 2 diabetes. Diabetes Care 2006 Jun; 29(6): 1269–74
Philis-Tsimikas A, Charpentier G, Clauson P, et al. Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly controlled type 2 diabetes. Clin Ther 2006 Oct; 28(10): 1569–81
Rasšlová K, Bogoev M, Raz I, et al. Insulin detemir and insulin aspart: a promising basal-bolus regimen for type 2 diabetes. Diabetes Res Clin Pract 2004 Nov; 66(2): 193–201
Hollander P, Cooper J, Bregnhøj J, et al. A 52-week, multinational, open-label, parallel-group, noninferiority, treat-to-target trial comparing insulin detemir with insulin glargine in a basal-bolus regimen with mealtime insulin aspart in patients with type 2 diabetes. Clin Ther 2008 Nov; 30(11): 1976–87
Raskin P, Gylvin T, Weng W, et al. Comparison of insulin detemir and insulin glargine using a basal-bolus regimen in a randomized, controlled clinical study in patients with type 2 diabetes. Diabetes Metab Res Rev 2009 Sep; 25(6): 542–8
Rosenstock J, Davies M, Home PD, et al. A randomised, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetologia 2008 Mar; 51(3): 408–16
Swinnen SG, Dain M-P, Aronson R, et al. A 24-week, randomized, treat-to-target trial comparing initiation of insulin glargine once-daily with insulin detemir twice-daily in patients with type 2 diabetes inadequately controlled on oral glucose-lowering drugs. Diabetes Care 2010 Jun; 33(6): 1176–8
Fogelfeld L, Dharmalingam M, Robling K, et al. A randomized, treat-to-target trial comparing insulin lispro protamine suspension and insulin detemir in insulin-naive patients with type 2 diabetes. Diabet Med 2010 Feb; 27(2): 181–8
Holman RR, Farmer AJ, Davies MJ, et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med 2009 Oct 29; 361(18): 1736–47
Liebl A, Prager R, Binz K, et al. Comparison of insulin analogue regimens in people with type 2 diabetes mellitus in the PREFER Study: a randomized controlled trial. Diabetes Obes Metab 2009 Jan; 11(1): 45–52
Davies M, Heller SR, Sreenan S, et al. Once-weekly exenatide versus once or twice daily insulin detemir: randomized, open-label clinical trial of efficacy and safety in patients with type 2 diabetes inadequately controlled with metformin ± sulfonylureas [abstract no. 40-LB]. Diabetes 2012 Jun; 61 Suppl. 1A: LB11
DeVries JH, Bain SC, Rodbard HW, et al. Sequential intensification of metformin treatment in type 2 diabetes with liraglutide followed by randomized addition of basal insulin prompted by A1C targets. Diabetes Care 2012 Jul; 35(7): 1446–54
Hollander P, Raslova K, Skjøth TV, et al. Efficacy and safety of insulin detemir once daily in combination with sitagliptin and metformin: the TRANSITION randomized controlled trial. Diabetes Obes Metab 2011 Mar; 13(3): 268–75
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 Jun; 11(6): 623–31
Hollander PA, Piletiç M, Silver HJ, et al. Weight change upon initiation of insulin detemir treatment with or without dietary intervention [abstract no. 939]. Diabetologia 2012 Oct; 55 Suppl. 1: S385–6
Holman RR, Thorne KI, Farmer AJ, et al. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med 2007 Oct 25; 357(17): 1716–30
Lüddeke H-J, Sreenan S, Aczel S, et al. PREDICTIVE± — a global, prospective observational study to evaluate insulin detemir treatment in types 1 and 2 diabetes: baseline characteristics and predictors of hypoglycaemia from the European cohort. Diabetes Obes Metab 2007 May; 9(3): 428–34
Dornhorst A, Lüddeke H-J, Sreenan S, et al. Safety and efficacy of insulin detemir in clinical practice: 14-week follow-up data from type 1 and type 2 diabetes patients in the PREDICTIVE± European cohort. Int J Clin Pract 2007 Mar; 61(3): 523–8
Dornhorst A, Lüddeke H-J, Honka M, et al. Safety and efficacy of insulin detemir basal-bolus therapy in type 1 diabetes patients: 14-week data from the European cohort of the PREDICTIVE study. Curr Med Res Opin 2008 Feb; 24(2): 369–76
Dornhorst A, Lüddeke H-J, Sreenan S, et al. Insulin detemir improves glycaemic control without weight gain in insulin-naive patients with type 2 diabetes: subgroup analysis from the PREDICTIVE± study. Int J Clin Pract 2008 Apr; 62(4): 659–65
Meneghini LF, Dornhorst A, Sreenan S, et al. Once-daily insulin detemir in a cohort of insulin-naïve patients with type 2 diabetes: a sub-analysis from the PREDICTIVE study. Curr Med Res Opin 2009 Apr; 25(4): 1029–35
Hermansen K, Lund P, Clemmensen K, et al. 3-Month results from Denmark within the globally prospective and observational study to evaluate insulin detemir treatment in type 1 and type 2 diabetes: the PREDICTIVE study. Rev Diabet Stud 2007; 4(2): 89–97
Kurtoglu S, Atabek ME, Dizdarer C, et al. Insulin detemir improves glycemic control and reduces hypoglycemia in children with type 1 diabetes: findings from the Turkish cohort of the PREDICTIVE± observational study. Pediatr Diabetes 2009 Sep; 10(6): 401–7
Marre M, Pinget M, Gin H, et al. Insulin detemir improves glycaemic control with less hypoglycaemia and no weight gain: 52-week data from the PREDICTIVE± study in a cohort of French patients with type 1 or type 2 diabetes. Diabetes Metab 2009 Dec; 35(6): 469–75
Meneghini LF, Rosenberg KH, Koenen C, et al. Insulin detemir improves glycaemic control with less hypoglycaemia and no weight gain in patients with type 2 diabetes who were insulin naive or treated with NPH or insulin glargine: clinical practice experience from a German subgroup of the PREDICTIVE study. Diabetes Obes Metab 2007 May; 9(3): 418–27
Perriello G, Caputo S, De Pergola G, et al. Improved glycemic control with weight loss and a low risk of hypoglycemia with insulin detemir: insights from the Italian cohort of the PREDICTIVE study after 6-month observation in type 2 diabetic subjects. Expert Opin Pharmacother 2011 Nov; 12(16): 2449–55
Preumont V, Buysschaert M, De Beukelaer S, et al. Insulin detemir in routine clinical practice: a 26-week follow-up in type 1 diabetic patients from the Belgian PREDICTIVE cohort. Acta Clin Belg 2009 Jan-Feb; 64(1): 49–55
Dornhorst A, Lüddeke H-J, Koenen C, et al. Transferring to insulin detemir from NPH insulin or insulin glargine in type 2 diabetes patients on basal-only therapy with oral antidiabetic drugs improves glycaemic control and reduces weight gain and risk of hypoglycaemia: 14-week follow-up data from PREDICTIVE±. Diabetes Obes Metab 2008 Jan; 10(1): 75–81
Khunti K, Caputo S, Damci T, et al. The safety and efficacy of adding once-daily insulin detemir to oral hypoglycaemic agents in patients with type 2 diabetes in a clinical practice setting in ten countries. Diabetes Obes Metab. Epub 2012 Jul 25
Khunti K, Damci T, Meneghini L, et al. Study of Once Daily Levemir (SOLVE): insights into the timing of insulin initiation in people with poorly controlled type 2 diabetes in routine clinical practice. Diabetes Obes Metab 2012 Jul; 14(7): 654–61
Garber AJ, Clauson P, Pedersen CB, et al. Lower risk of hypoglycemia with insulin detemir than with neutral protamine Hagedorn insulin in older persons with type 2 diabetes: a pooled analysis of phase III trials. J Am Geriatr Soc 2007 Nov; 55(11): 1735–40
Niskanen L, Virkamäki A, Hansen JB, et al. Fasting plasma glucose variability as a marker of nocturnal hypoglycemia in diabetes: evidence from the PREDICTIVE± study. Diabetes Res Clin Pract 2009 Nov; 86(2): e15–8
American Diabetes Association. Standards of medical care in diabetes: 2012. Diabetes Care 2012 Jan; 35 Suppl. 1: S11–63
Sørensen LP, Brock B, Mengel A, et al. Similarity of pharmacodynamic effects of a single injection of insulin glargine, insulin detemir and NPH insulin on glucose metabolism assessed by 24-h euglycaemic clamp studies in healthy humans. Diabet Med 2010 Jul; 27(7): 830–7
Raslova K. An update on the treatment of type 1 and type 2 diabetes mellitus: focus on insulin detemir, a long-acting human insulin analog. Vasc Health Risk Manag 2010; 6: 399–410
Morales J. Defining the role of insulin detemir in basal insulin therapy. Drugs 2007; 67(17): 2557–84
Peterson GE. Intermediate and long-acting insulins: a review of NPH insulin, insulin glargine and insulin detemir. Curr Med Res Opin 2006 Dec; 22(12): 2613–9
Arnolds S, Kuglin B, Kapitza C, et al. How pharmacokinetic and pharmacodynamic principles pave the way for optimal basal insulin therapy in type 2 diabetes. Int J Clin Pract 2010 Sep; 64(10): 1415–24
Muggeo M, Verlato G, Bonora E, et al. Long-term instability of fasting plasma glucose, a novel predictor of cardiovascular mortality in elderly patients with non-insulin-dependent diabetes mellitus: the Verona Diabetes Study. Circulation 1997 Sep 16; 96(6): 1750–4
Meneghini L, Koenen C, Weng W, et al. The usage of a simplified self-titration dosing guideline (303 algorithm) for insulin detemir in patients with type 2 diabetes: results of the randomized, controlled PREDICTIVE± 303 study. Diabetes Obes Metab 2007 Nov; 9(6): 902–13
Selam J-L, Meneghini LF. Basal-bolus therapy with insulin detemir using the 303 algorithm in the US PREDICTIVE 303 trial. Adv Ther 2009 Feb; 26(2): 194–207
Selam J-L, Koenen C, Weng W, et al. Improving glycemic control with insulin detemir using the 303 algorithm in insulin naïve patients with type 2 diabetes: a subgroup analysis of the US PREDICTIVE 303 study. Curr Med Res Opin 2008 Jan; 24(1): 11–20
True MW. An analysis of dosing equivalence of insulin detemir and insulin glargine: more evidence? J Diabetes Sci Technol 2010 Jan; 4(1): 155–7
King AB. No higher dose requirements with insulin detemir than glargine in type 2 diabetes: a crossover, double-blind, and randomized study using continuous glucose monitoring. J Diabetes Sci Technol 2010 Jan; 4(1): 151–4
King AB. Once-daily insulin detemir is comparable to once-daily insulin glargine in providing glycaemic control over 24 h in patients with type 2 diabetes: a double-blind, randomized, crossover study. Diabetes Obes Metab 2009 Jan; 11(1): 69–71
Nelson SE. Detemir as a once-daily basal insulin in type 2 diabetes. Clin Pharmacol 2011; 3: 27–37
Kerney DL, Paradis D, Brunton S. Patient perceptions of insulin detemir as reported through patient telephone surveys. Curr Med Res Opin 2007 Sep; 23(9): 2043–9
Kabadi UM. Deleterious outcomes after abrupt transition from insulin glargine to insulin detemir in patients with type 1 diabetes mellitus. Clin Drug Invest 2008; 28(11): 697–701
Kabadi U. Iowa medicaid 2: lapse of glycemic control on abrupt transition from insulin glargine to insulin detemir in type 2 diabetes mellitus. J Diabetes Mellit 2011; 1(4); 124–8
Tunis SL, Minshall ME, Conner C, et al. Cost-effectiveness of insulin detemir compared to NPH insulin for type 1 and type 2 diabetes mellitus in the Canadian payer setting: modeling analysis. Curr Med Res Opin 2009 May; 25(5): 1273–84
Valentine WJ, Aagren M, Haglund M, et al. Evaluation of the long-term cost-effectiveness of insulin detemir compared with neutral protamine hagedorn insulin in patients with type 1 diabetes using a basal-bolus regimen in Sweden. Scand J Public Health 2011 Feb; 39(1): 79–87
Gschwend MH, Aagren M, Valentine WJ. Cost-effectiveness of insulin detemir compared with neutral protamine Hagedorn insulin in patients with type 1 diabetes using a basal-bolus regimen in five European countries. J Med Econ 2009 Jun; 12(2): 114–23
Valentine WJ, Jendle J, Saraheimo M, et al. Evaluating the cost-effectiveness of reduced mild hypoglycaemia in subjects with type1 diabetes treated with insulin detemir or NPH insulin in Denmark, Sweden, Finland and the Netherlands. Diabet Med 2012 Mar; 29(3): 303–12
Valentine WJ, Erny-Albrecht KM, Ray JA, et al. Therapy conversion to insulin detemir among patients with type 2 diabetes treated with oral agents: a modeling study of cost-effectiveness in the United States. Adv Ther 2007 Mar/Apr; 24(2): 273–90
Valentine WJ, Goodall G, Aagren M, et al. Evaluating the cost-effectiveness of therapy conversion to insulin detemir in patients with type 2 diabetes in Germany: a modelling study of long-term clinical and cost outcomes. Adv Ther 2008 Jun; 25(6): 567–84
Yang L, Christensen T, Sun F, et al. Cost-effectiveness of switching patients with type 2 diabetes from insulin glargine to insulin detemir in Chinese setting: a health economic model based on the PREDICTIVE study. Value Health 2012 Jan–Feb; 15 (1 Suppl.): S56–9
Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: a consensus report. Diabetes Care 2010 Jul; 33(7): 1674–85
Evans M, Schumm-Draeger PM, Vora J, et al. A review of modern insulin analogue pharmacokinetic and pharmacodynamic profiles in type 2 diabetes: improvements and limitations. Diabetes Obes Metab 2011 Aug; 13(8): 677–84
Dejgaard A, Lynggaard H, Rastam J, et al. No evidence of increased risk of malignancies in patients with diabetes treated with insulin detemir: a meta-analysis. Diabetologia 2009 Dec; 52(12): 2507–12
Gerstein HC, Bosch J, Dagenais GR, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012 Jul 26; 367(4): 319–28
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Various sections of the manuscript reviewed by: M. Evans, Department of Medicine, University Hospital Llandough, Cardiff, Wales; U.M. Kabadi, Department of Medicine, University of Iowa, Iowa City, IA, USA; E. Karnieli, Institute of Endocrinology, Diabetes, and Metabolism, Rambam Medical Center, R.B. Rappaport Faculty of Medicine-Technion, Haifa, Israel; A.D. Mooradian, Department of Medicine, University of Florida College of Medicine, Jacksonville, FL, USA; K. Rasšlová, Metabolic Center Ltd and Slovak Medical University, Bratislava, Slovakia; S.A. Ross, University of Calgary, LMC Endocrinology Centres, Calgary, AB, Canada.
Data Selection
Sources: Medical literature (including published and unpublished data) on ‘insulin detemir’ was identified by searching databases (including MEDLINE and EMBASE) for articles published since 1996, bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.
Search strategy: MEDLINE and EMBASE search terms were ‘insulin detemir’ and (‘diabetes mellitus, type 1’ or ‘insulin dependent diabetes mellitus’ or ‘diabetes mellitus, type 2’ or ‘non insulin dependent diabetes mellitus’ or ‘diabetes mellitus’). Searches were last updated 15 October 2012.
Selection: Studies in patients with type 1 or type 2 diabetes mellitus who received insulin detemir. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: Insulin detemir, type 1 diabetes mellitus, type 2 diabetes mellitus, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.
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Keating, G.M. Insulin Detemir. Drugs 72, 2255–2287 (2012). https://doi.org/10.2165/11470200-000000000-00000
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DOI: https://doi.org/10.2165/11470200-000000000-00000