Clinical Studies
Efficacy of 24-Week Monotherapy With Acarbose, Metformin, or Placebo in Dietary-Treated NIDDM Patients: The Essen-II Study

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Abstract

PURPOSE: To compare the therapeutic potential of acarbose, metformin, or placebo as first line treatment in patients with non-insulin-dependent diabetes mellitus (NIDDM).

PATIENTS AND METHODS: Ninety-six patients with NIDDM (35–70 years of age, body mass index (BMI) ≤ 35 kg/m2, insufficiently treated with diet alone, glycated hemoglobin (HbA1C; 7% to 11%) were randomized into 3 groups and treated for 24 weeks with acarbose, 3 × 100 mg/day, or metformin, 2 × 850 mg/day, or placebo. Efficacy, based on HbA1C (primary efficacy criterion), fasting blood glucose (BG) and insulin, 1 hour postprandial BG and insulin (after standard meal test), postprandial insulin increase, plasma lipid profile, and tolerability, based on subjective symptoms and laboratory values were determined every 6 weeks. Analysis of covariance was performed for endvalues with adjustment on baseline values. Ninety-four patients were valid for efficacy evaluation.

RESULTS: Both active drugs showed the same improvement of efficacy criteria compared with placebo. Baseline adjusted means at endpoint were as follows: BG, fasting and 1 hour postprandial, 9.2 mM and 10.9 mM with placebo, 7.6 mM and 8.7 mM with acarbose, and 7.8 mM and 9.0 mM with metformin; HbA1C was 9.8% with placebo, 8.5% with acarbose, and 8.7% with metformin. Comparisons: acarbose versus placebo and metformin versus placebo were statistically significant, but not acarbose versus metformin.

No effect on fasting insulin could be observed. Relative postprandial insulin increase was 1.90 with placebo, 1.09 with acarbose, and 1.03 with metformin. Comparisons: acarbose versus placebo and metformin versus placebo were statistically significant, but not acarbose versus metformin.

With respect to lipid profile, acarbose was superior to metformin. Low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio increased by 14.4% with placebo, was unchanged with metformin, but decreased by 26.7% with acarbose. Comparisons: acarbose versus placebo and acarbose versus metformin were statistically significant, but not metformin versus placebo.

Slight body weight changes were observed with acarbose (−0.8 kg) and metformin (−0.5 kg), but not with placebo. Acarbose led to mild or moderate intestinal symptoms in 50% of the patients within the first 4 weeks, but in only 13.8% of the patients within the last 4 weeks.

CONCLUSIONS: Acarbose and metformin are effective drugs for the first line monotherapy of patients with NIDDM. With respect to plasma lipid profile, especially HDL cholesterol, LDL cholesterol and LDL/HDL cholesterol ratio, acarbose may be superior to metformin.

Section snippets

Patients and Methods

The study was planned biometrically as a randomized three-arm (placebo, acarbose, metformin) group comparison that was double-blind with respect to acarbose/placebo treatment and single-blind with respect to metformin treatment. By choosing a single-blind design, a double-dummy design was avoided and patients’ treatment was kept close to everyday life.

The study was conducted in four internal practices in Essen, Germany. The randomization plan was generated by electronic data processing for 16

Actual Dosage and Duration of Treatment

All 3 test substances were dosed as planned, compliance was 98% (pill counting). The duration of treatment was 168.5 ± 8.1 days in the placebo group, 166.5 ± 11.1 days in the acarbose group, and 169.5 ± 2.7 days in the metformin group (means ± SD).

Efficacy

The courses of fasting and postprandial blood glucose are shown in Fig. 1. No change was observed during 24 weeks of placebo treatment, but a marked decrease could be seen for both fasting and postprandial BG with acarbose and metformin.

The baseline

Conclusions

Both acarbose and metformin are recommended for treatment of NIDDM as first-line single drugs when diet alone fails, as well as in combination with other antidiabetic drugs, by the European NIDDM Policy Group,[14]the Asian-Pacific NIDDM Policy Group,[15]and by the American Diabetes Association (ADA).[16]The results of this study demonstrate the beneficial effect of both drugs as first-line treatment on parameters of metabolic control in patients with NIDDM previously treated with diet alone.

Acknowledgements

We thank Drs. Uwe-Hans Day, Georg Garanin, and Eckard Lohr for collaboration in carrying out the study, Dipl Stat C. Norenberg for statistical evaluation, T. Borth for careful monitoring, M. Bungert, and M. Grünwald for editorial help.

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    This work was supported by Bayer AG, Leverkusen, Germany.

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