Comparison of Basal Insulin Added to Oral Agents Versus Twice-Daily Premixed Insulin as Initial Insulin Therapy for Type 2 Diabetes

  1. Hans U. Janka, MD1,
  2. Gerd Plewe, MD1,
  3. Matthew C. Riddle, MD2,
  4. Christine Kliebe-Frisch, PHD3,
  5. Matthias A. Schweitzer, MD3 and
  6. Hannele Yki-Järvinen, MD4
  1. 1Zentralkrankenhaus, Bremen-Nord, Bremen, Germany
  2. 2Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University, Portland, Oregon
  3. 3Aventis Pharma Deutschland, Bad Soden, Germany
  4. 4Department of Medicine, University of Helsinki, Helsinki, Finland
  1. Address correspondence and reprint requests to Prof. Hans U. Janka, Zentralkrankenhaus, Bremen-Nord, II Medizinische Abteilung, Hammersbecker Str. 228, 28755 Bremen, Germany. E-mail: hans.janka{at}klinikum-bremen-nord.de

Abstract

OBJECTIVE—To compare the efficacy and safety of adding once-daily basal insulin versus switching to twice-daily premixed insulin in type 2 diabetic patients insufficiently controlled by oral antidiabetic agents (OADs).

RESEARCH DESIGN AND METHODS—In a 24-week, multinational, multicenter, open, parallel group clinical trial, 371 insulin-naïve patients with poor glycemic control (fasting blood glucose [FBG] ≥120 mg/dl, HbA1c 7.5–10.5%) on OADs (sulfonylurea plus metformin) were randomized to once-daily morning insulin glargine plus glimepiride and metformin (glargine plus OAD) or to 30% regular/70% human NPH insulin (70/30) twice daily without OADs. Insulin dosage was titrated to target FBG ≤100 mg/dl (both insulins) and predinner blood glucose ≤100 mg/dl (70/30 only) using a weekly forced-titration algorithm.

RESULTS—Mean HbA1c decrease from baseline was significantly more pronounced (−1.64 vs. −1.31%, P = 0.0003), and more patients reached HbA1c ≤7.0% without confirmed nocturnal hypoglycemia (45.5 vs. 28.6%, P = 0.0013) with glargine plus OAD than with 70/30. Similarly, FBG decrease was greater with glargine plus OAD (adjusted mean difference −17 mg/dl [–0.9 mmol/l], P < 0.0001), and more patients reached target FBG ≤100 mg/dl with glargine plus OAD than with 70/30 (31.6 vs. 15.0%, P = 0.0001). Glargine plus OAD patients had fewer confirmed hypoglycemic episodes than 70/30 patients (mean 4.07 vs. 9.87/patient-year, P < 0.0001).

CONCLUSIONS—Initiating insulin treatment by adding basal insulin glargine once daily to glimepiride plus metformin treatment was safer and more effective than beginning twice-daily injections of 70/30 and discontinuing OADs in type 2 diabetic patients inadequately controlled with OADs.

Footnotes

  • H.U.J., M.C.R., and H.Y.-J. have received honoraria and consulting fees from Aventis.

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

    See accompanying editorial, p. 494.

    • Accepted October 20, 2004.
    • Received July 28, 2004.
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