An update on the treatment of type 1 and type 2 diabetes mellitus: focus on insulin detemir, a long-acting human insulin analog

Figures & data

Table 1 Recent randomized trials in type 1 diabetes mellitus

Study	Therapy and objectives	Summary of results
Pieber et al^Citation23 N = 320 26-week Randomized, multicenter, open-label, parallel-group	Comparison of glycemic control and risk of hypoglycemia of twice-daily insulin detemir with once-daily insulin glargine	Det vs Glar, P HbA1c −0.6% vs −0.5%, ns FPG 7.7 vs 7.0, 0.001 Severe and noctur −72% vs −32%, 0.05 hypoglycemia Within-subject variability, ns Overall hypoglycemia ns Body weight, ns
Robertson et al^Citation24 N = 347 children 26-week Randomized (2:1), multicenter, open-label, parallel-group	Efficacy and safety of detemir vs NPH. Once- or twice-daily according to the pre-study regimen, plus premeal insulin aspart	Det vs NPH, P HbA1c −0.8% vs −0.8%, ns FPG 8.4 9.6 0.02 Within-subject SD 3.3 vs SD 4.3, 0.001 variability BMI Z-score 0.08, 0.26, 0.001 Overall hypoglycemia, ns Noctur hypoglycemia was 26% less with detemir (P = 0.04)
Bartley et al^Citation28 N = 497 24-month Randomized(2:1), multicenter, open-label, parallel-group, treat-to-target	Long-term efficacy and safety of detemir vs NPH, plus premeal insulin aspart. Basal insulin initiated once daily, titrated based on PG levels, aiming for pre-breakfast and pre-dinner targets ≤ 6.0 mmol/L	Det vs NPH, P HbA1c −0.94% vs −0.72%, 0.02 FPG 8.3 9.4 0.02 Body weight +1.7 +2.7, 0.02 Major and noctur −69% vs −46%, 0.001 hypoglycemia
Le Floch et al^Citation26 N = 520 7-month Randomized, multicenter, open-label, treat-to-target	Comparison of the efficacy and safety of once- and twice-daily detemir, plus premeal insulin aspart. After 4-month therapy twice-daily switched to once-daily	Det once vs Det twice, P HbA1c 8.1% vs 8%, ns Detemir doses 29 vs 39, 0.001 No difference in the body weight and the ftrequency of hypoglycemia
Heller et al^Citation27 N = 443 52-week Randomized (2:1), multicenter, open-label, treat-to-target non-inferiority	Comparison of detemir with glargine, plus premeal insulin aspart. Detemir initiated once daily, titrated based on PG levels, if not achieved the pre-dinner targets patients switched to twice-daily detemir	Det vs Glar, P HbA1c −0.53% vs −0.54%, ns HbA1c <7%, 32% vs 29%, ns without major hypoglycemia FPG 8.6 vs 8.8, ns No difference in hypoglycemia No difference in body weight Total basal doses 0.4 IU/kg vs 0.33 IU/kg, ns 34.2% participants completed on once-daily Det with mean daily dose of 0.33 U/kg and 65.8 of them on twice-daily with mean daily dose of 0.47 IU/kg. Mean daily dose of Glar was 0.33 IU/kg

Abbreviations: Det, detemir; Glar, glargine; Det once, detemir once-daily; Det twice, detemir twice-daily; FPG, fasting plasma glucose; noctur, nocturnal; NPH, neutral protamine Hagedorn; ns, not significant; PG, plasma glucose; SD, standard deviation.

Table 2 Randomized trials comparing insulin detemir and insulin glargine in type 2 diabetes mellitus (DM)

Study	Therapy and objectives	Summary of results
Hollander et al^Citation39 N = 319 52-week randomized (2:1), multicenter, open-label, parallel-group, noninferiority, treat-to-target	Comparison of Det and Glar added to type 2DM who had been receiving an OAD or insulin, with or without OADs. Det, QD (evening) or BID (morning + evening) or Glar, QD (evening), plus premeal insulin aspart Existing OADs were continued but insulin secretagogs and a-glucosidase inhibitors were discontinued	Det vs Glar, P HbA1c −1.52% vs −1.68%, ns Body weight (kg) +2.8 +3.8.0.05 Within-subject variability, ns. Overall hypoglycemia, ns. Overall, the Det-treated subjects used more insulin than the Glar-treated subjects (0.82 IUs/kg vs 0.59 IU/kg, respectively), but this difference disappeared when comparing only single-dose Det-treated subjects who used an average daily basal insulin dose of 0.69 U/kg
Rosenstock et al^Citation40 n = 582 52-week randomized, multicenter, open-label, treat-to-target	Comparison of Det and Glar added to OAD in insulin-naive patients Det, QD (evening) or BID (morning + evening) or Glar, QD (evening). Initiate therapy at 12 units, titrate to FPG target of <6 mmol/L	Det vs Glar, P HbA1c −1.4% vs −1.5%, ns Body weight (kg) +3.0 vs +3.9, 0.01 Within-subject variability, ns Overall hypoglycemia, ns 45% of participants completed on once-daily Det with mean daily dose of 0.52 IU/kg and 55% of them on twice-daily with mean daily dose of 1.0 IU/kg. Mean daily dose of Glar was 0.44 IU/kg
Raskin et al^Citation41 N = 385 26-week randomized (2:1), multicenter, open-label, parallel-group, noninferiority, treat-to-target	Comparison of the efficacy and safety of Det and Glar in a basal-bolus (premeal insulin aspart) regimen in type 2DM	Det vs Glar, P HbA1c −1.1% vs–1.3%, ns Body weight (kg) + 1.2 vs +2.7, 0.01 Within-subject variability, ns Overall hypoglycemia ns 87.4% of Det-treated patients remained on a once-daily basal insulin regimen at comparable basal insulin dosage. Mean basal insulin doses were comparable between treatments (Det 0.81 vs Glar 0.75 IU/kg, P =0.1)
Swinnen et al^Citation42 N = 973 24-week randomized, multicenter, open-label, parallel-group, noninferiority, treat-to-target	Comparison of percentage of patients reaching HbA1c <7% without symptomatic hypoglycemia ≤3.1 mmol/L in insulin-naive type 2 DM on stable OGLDs who were randomized to Glar once-daily or Det twice-daily	Det vs Glar, P HbA1c −1.54% vs −1.46%, ns Body weight (kg) 0.6 vs 1.4, 0.001 Overall hypoglycemia ns 27.5% and 25.6% of patients reached HbA1c < 7% without symptomatic hypoglycemia ≤3.1 mmol/L. More patients with Det reached HbA1c <6.5% (P = 0.017). Glar doses were lower than Det doses: 43.5 vs 76.5 IU/d (P < 0.001)

Abbreviations: Det, detemir; Glar P, glargine; Det once, detemir once-daily; Det twice, detemir twice-daily; FPG, fasting plasma glucose; ns, not significant; OAD, oral anti-diabetic therapy; OGLD, oral glucose-lowering drugs; QD, once daily; BID, twice daily.

PieberTRTreichelHCHompeschBComparison of insulin detemir and insulin glargine in subjects with Type 1 diabetes using intensive insulin therapyDiabet Med200724663564217381500

 PubMed Web of Science ®Google Scholar

RobertsonKJSchoenleEGucevZMordhorstLGallMALudviqssonJInsulin detemir compared with NPH insulin in children and adolescents with Type 1 diabetesDiabet Med20072412734

 PubMed Web of Science ®Google Scholar

BartleyPCBogoevMLarsenJPhilotheouALong-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 trialDiabet Med200825444244918387078

 PubMed Web of Science ®Google Scholar

Le FlochJPLévyMMosnier-PudarHAssessment of Detemir Administration in Progressive Treat-to-Target Trial (ADAPT) Study Group 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 Care20093213237

 PubMed Web of Science ®Google Scholar

HellerSKoenenCBodeBComparison 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 trialClin Ther2009311020862097

 PubMed Web of Science ®Google Scholar

HollanderPCooperJBregnhøjJPedersenCBA 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 diabetesClin Ther200830111976198719108786

 PubMed Web of Science ®Google Scholar

RosenstockJDaviesMHomePDLarsenJKoenenCSchernthanerGA 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 diabetesDiabetologia2008513408416

 PubMed Web of Science ®Google Scholar

RaskinPGylvinTWengWChaykinLComparison of insulin detemir and insulin glargine using a basal-bolus regimen in a randomized, controlled clinical study in patients with type 2 diabetesDiabetes Metab Res Rev2009256542548

 PubMed Web of Science ®Google Scholar

SwinnenSGDainMPAronsonRA 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 drugsDiabetes Care201033 [Epub ahead of print].

 PubMed Web of Science ®Google Scholar