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

Kjeld Hermansen; Melanie Davies; Taudeusz Derezinski; Gabrielle Martinez Ravn; Per Clauson; Philip Home

doi:10.2337/dc05-1365

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

Kjeld Hermansen, MD1,
Melanie Davies, MD2,
Taudeusz Derezinski, MD3,
Gabrielle Martinez Ravn4,
Per Clauson4,
Philip Home, DM, DPHIL5 and
on behalf of the Levemir Treat-to-Target Study Group

¹Department of Endocrinology and Metabolism, Aarhus Sygehus THG, Aarhus University Hospital, Aarhus, Denmark
²University Hospitals of Leicester, Leicester Royal Infirmary, Leicester, U.K.
³Out-Patient Clinic, NZOZ Eskulap, Gniewkowo, Poland
⁴Out-Patient Clinic, Novo Nordisk, Bagsværd, Denmark
⁵School of Medical Sciences–Diabetes, University of Newcastle upon Tyne, Newcastle upon Tyne, U.K.

Address correspondence and reprint requests to Professor Kjeld Hermansen, Department of Endocrinology and Metabolism, Aarhus Sygehus THG, Aarhus University Hospital, DK-8000 Aarhus C, Denmark. E-mail: kjeld.hermansen{at}as.aaa.dk

Abstract

OBJECTIVE—To assess efficacy and tolerability of insulin detemir or NPH insulin added to oral therapy for type 2 diabetes in a treat-to-target titration protocol.

RESEARCH DESIGN AND METHODS—Individuals (n = 476) with HbA_1c (A1C) 7.5–10.0% were randomized to addition of twice-daily insulin detemir or NPH insulin in a parallel-group, multicenter trial. Over 24 weeks, insulin doses were titrated toward prebreakfast and predinner plasma glucose targets of ≤6.0 mmol/l (≤108 mg/dl). Outcomes assessed included A1C, percentage achieving A1C ≤7.0%, risk of hypoglycemia, and body weight.

RESULTS—At 24 weeks, A1C had decreased by 1.8 and 1.9% (from 8.6 to 6.8 and from 8.5 to 6.6%) for detemir and NPH, respectively (NS). In both groups, 70% of participants achieved an A1C ≤7.0%, but the proportion achieving this without hypoglycemia was higher with insulin detemir than with NPH insulin (26 vs. 16%, P = 0.008). Compared with NPH insulin, the risk for all hypoglycemia with insulin detemir was reduced by 47% (P < 0.001) and nocturnal hypoglycemia by 55% (P < 0.001). Mean weight gain was 1.2 kg with insulin detemir and 2.8 kg with NPH insulin (P < 0.001), and the difference in baseline-adjusted final weight was −1.58 (P < 0.001).

CONCLUSIONS—Addition of basal insulin to oral drug therapy in people with suboptimal control of type 2 diabetes achieves guideline-recommended A1C values in most people with aggressive titration. Insulin detemir compared with NPH insulin achieves this with reduced hypoglycemia and less weight gain.

Footnotes

Additional information for this article can be found in an online appendix at http://care.diabetesjournals.org.

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Accepted February 18, 2006.
- Received July 22, 2005.
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