Critical appraisal of the safety and efficacy of insulin detemir in glycemic control and cardiovascular risk management in diabetics

Figures & data

Figure 1 Molecular structure of insulin detemir.

Figure 2 Mean 24-hour action profiles of three doses of insulin detemir and insulin glargine (A: 0.4 U/kg; B: 0.8 U/kg; C: 1.4 U/kg) in a glycemic clamp study in patients with insulin-requiring type 2 diabetes (fasting C-peptide concentration ≤ 1 nmol/L). Reprinted from Klein O, Lynge J, Endahl L, Damholt B, Nosek L, Heise T. 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;9:290–299.³⁴ Copyright © 2007, with permission from John Wiley and Sons.³⁴

Table 1 Studies conducted in patients with type 1 diabetes

Study (reference)	Comparator	Additional glucose-lowering treatment	Trial duration (weeks)	Participants (n, ITT)	Baseline HbA1c (%)	Endpoint HbA1c (%)	Mean weight change (kg)	Hypoglycemia (relative risk for detemir)		Mean endpoint SMFPG (mmol/L)	Within-patient SD in FPG (mmol/L)
					Comparator	Comparator	Comparator	24 hours	Nocturnal	Comparator	Comparator
a Home et al^Citation48	NPH	Insulin aspart	16	137/139	8.55/8.74	7.75/7.78	+0.02/+0.24	0.75*/0.68**	0.74/0.47***	8.28/8.26	2.95/2.91
				132	8.52	7.94	+0.86*			9.05**	3.49***
Russell-Jones et al^Citation52	NPH	Regular human insulin	26	491	8.35	8.30	−0.23	0.94	0.74**	7.56	2.82
				256	8.35	8.41	+0.31*			8.47***	3.60***
a Pieber et al^Citation50	NPH	Insulin aspart	16	139/132	8.01/8.13	7.67/7.65	−0.6/+0.1	Not reported	Not reported	8.20/8.00	2.49/2.61
				129	8.08	7.73	+0.7*,***			8.31	3.09***
Kølendorf et al^Citation49 (crossover)	NPH	Insulin aspart	2 × 16	130	7.90	7.60	N/A	0.82**	0.50***	7.63	2.69
					7.90	7.60	N/A			8.66***	3.23***
b Robertson et al^Citation56	NPH	Insulin aspart	26	232	8.80	8.0	N/A	0.89	0.74*	8.40	3.3
				115	8.70	7.90				9.60*	4.3***
Bartley et al^Citation54	NPH	Insulin aspart	104	331	8.3	7.36	+1.7	0.74	0.54***	8.35c	2.18
				166	8.4	7.58*	+2.7			9.43*,c	2.52***
Heller et al^Citation59	Insulin glargine	Insulin aspart	58	299	8.1	7.57	+0.36	0.94	1.12	8.58	2.55
				144	8.1	7.56	+0.42			8.81	2.39

a Notes: Data for detemir in Home et al⁴⁸ are given as 12-hourly/morning + bedtime injection regimens. Data for detemir in Pieber et al⁵⁰ are given as morning + dinner time/morning + bedtime injection regimens;

b study included children and/or adolescents.

c Clinical (laboratory) measured FPG.

* P < 0.05;

** P < 0.01;

*** P < 0.001.

Abbreviations: FPG, fasting plasma glucose; NPH, neutral protamine Hagedorn insulin; HbA_1c, glycosylated hemoglobin; ITT, intent to treat; SMFPG, self-measured fasting plasma glucose; SD, standard deviation.

Table 2 Studies conducted in patients with type 2 diabetes

Study (reference)	Comparator	Additional glucose-lowering treatment	Trial duration (weeks)	No. participants (ITT) in the insulin detemir group	Baseline HbA1c (%)	Endpoint HbA1c (%)	Mean weight change (kg)	Hypoglycemia (relative risk for detemir)		Mean endpoint SMFPG (mmol/L)	Within-patient SD in FPG (mmol/L)
					Comparator	Comparator	Comparator	24 hours	Nocturnal	Comparator	Comparator
Haak et al^Citation63	NPH	Insulin aspart	26	341	7.9	7.6	+1.0	0.84	1.02	9.7	1.3
				164	7.8	7.5	+1.8*			9.6	1.4*
^dPhilis-Tsimikas et al^Citation65	NPH	OADs	20	165/169	9.08/8.88	7.50/7.40	+1.2/+0.7	0.68/0.47*	0.13***/0.35*	7.97/6.50	Not reported
				164	9.15	7.35	+1.6**			6.78	Not reported
Hermansen et al^Citation61	NPH	OADs	24	227	8.6	6.8	1.2	0.53***	0.45***	6.9a	0.88
				225	8.5	6.6	2.8***	0.94	1.05	6.6a	0.99**
Rosenstock et al^Citation66	Insulin glargine	OADs	52	291	8.64	7.16	+3.0			7.14a	1.06
				291	8.62	7.12	+3.9**			6.98a	1.03
Hollander et al^Citation67	Insulin glargine	Insulin aspart	52	214	8.6	7.19	+2.8	0.75	0.63/1.15 (OD/BID)	7.05	1.36
				105	8.8	7.03	+3.8*			6.68	1.39

a Notes: Study also compared detemir OD in the morning with detemir OD in the evening. Results from both are shown here;

* P < 0.05;

** P < 0.01;

*** P < 0.001.

Abbreviations: FPG, fasting plasma glucose; NPH, neutral protamine Hagedorn insulin; HbA_1c, glycosylated hemoglobin; ITT, intent to treat; OAD, oral antidiabetic; OD, once daily; BID, twice daily; SMFPG, self-measured fasting plasma glucose; SD, standard deviation.

Table 3 Studies comparing an insulin analog basal-bolus regimen with a human insulin basal-bolus regimen

Analog regimens versus regular insulin regimens
Study (reference)	Comparator and additional glucose-lowering treatment	Trial duration (weeks)	Participants (n, ITT)	Baseline HbA1c (%)	Endpoint HbA1c (%)	Mean weight change (kg)	Hypoglycemia (relative risk for detemir)		Mean endpoint SMFPG (mmol/L)	Within-patient SD in FPG (mmol/L)
				Comparator	Comparator	Comparator	24 hours	Nocturnal	Comparator	Comparator
Hermansen et al^Citation53	NPH with human soluble insulin versus insulin detemir and insulin aspart	18	298 297	8.48 8.29	7.88 8.11***	−0.95 +0.07***	0.79*	0.45***	7.58 8.10*	2.60 3.04***
Rašlová et al^Citation64	NPH with human soluble insulin versus insulin detemir and insulin aspart in patients with type 2 diabetes	22	195 200	8.16 8.08	7.46 7.52	+0.51 +1.13	0.87	0.54*	7.28 7.32	1.20 1.54***

* P < 0.05;

** P < 0.01;

*** P < 0.001.

Abbreviations: ITT, intent to treat; NPH, neutral protamine Hagedorn insulin; SD, standard deviation; SMFPG, self-measured fasting plasma glucose. SD, standard deviation; FPG, fasting plasma glucose; SMFPG, self-measured fasting plasma glucose.

Figure 3 Weight change stratified by baseline body mass index in previously insulin-naïve patients adding basal insulin to oral antidiabetic therapy. A) In a comparative treat-to-target trial. B) In the observational PREDICTIVE study. Figure 3a reprinted from Philis-Tsimikas A. Tolerability, safety and adherence to treatment with insulin detemir injection in the treatment of type 2 diabetes. Patient Prefer Adherence. 2008;2:323–332.⁷⁹ Copyright 2008, with permission from Dove Medical Press Ltd. Figure 3b reprinted from Dornhorst A, Lüddeke HJ, Sreenan S, et al; PREDICTIVE Study Group. Insulin detemir improves glycaemic control without weight gain in insulin-naïve patients with type 2 diabetes: Subgroup analysis from the PREDICTIVE study. Int J Clin Pract. 2008;62:659–665.⁸¹ Copyright © 2008, with permission from John Wiley & Sons, Inc.

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