Assessment of Diabetes Control and Evaluation of the Efficacy of Niaspan Trial - ADVENT

Dec 07, 2004
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Date Published:
01/01/2002
Date Updated:
12/07/2004
Original Posted Date:
12/07/2004
References

Description:

The goal of the trial was to evaluate the safety and efficacy of treatment with niacin compared with placebo among type 2 diabetic patients with dyslipidemia.

Study Design

Study Design:

Patients Enrolled: 148
Mean Follow Up: 16 weeks
Mean Patient Age: Mean age 60 years
Female: 41

Patient Populations:

Age ≥21 years; stable type 2 diabetes, defined as a fasting blood glucose level of ≤200 mg/dl and an HbA1c level of ≤9% on two separate measures, and controlled by diet, oral hypoglycemic agents, or insulin; low-density lipoprotein cholesterol (LDL-C) level of ≥130 mg/dl, HDL-C level of ≤40 mg/dl, or triglyceride level of ≥200 mg/dl in patients treated with an HMG-CoA reductase inhibitor and LDL-C level of ≤130 mg/dl, HDL-C level of ≤40 mg/dl or a triglyceride level of ≥200 mg/dl in patients not treated with an HMG-CoA reductase inhibitor; and baseline aspartate aminotransferase and alanine aminotransferase levels ≤1.3 times the upper limit of the reference range

Primary Endpoints:

• Safety: change from baseline to week 16 in HbA1c level
• Efficacy: changes from baseline to week 16 in HDL-C and triglyceride levels

Drug/Procedures Used:

Patients were randomized to placebo (n=49), once-daily extended-release (ER) niacin 1000 mg/d (n=45) or ER niacin 1500 mg/d (n=52). Follow-up visits were conducted at weeks 4, 8, 12, and 16.

Concomitant Medications:

All concomitant hypoglycemic medications (including insulin) were allowed except troglitazone, a thiazolidinedione.

Principal Findings:

Concomitant statin therapy was used in 47% of patients. At week 16, high-density lipoprotein cholesterol (HDL-C) levels increased by 7.6 mg/dl in the 1000 mg group and 11.0 mg/dl in the 1500 mg group compared with 1.6 mg/dl in the placebo group (p<0.05 vs. placebo for both niacin doses). Triglyceride levels were reduced at the follow-up visits from 15% to 20% in the 1000 mg group and 28% to 36% in the 1500 mg group compared with 5% to 8% in the placebo group (p=NS for 1000 mg vs. placebo; p<0.05 for 1500 mg vs. placebo).

The mean changes from baseline at 16 weeks were +9% in the placebo group, +5% in the 1000 mg group (p=NS vs. placebo), and -7% in the 1500 mg group (p<0.05 vs. placebo). Mean HbA1c values at 16 weeks were 7.1% in the placebo group, 7.4% in the 1000 mg group, and 7.5% in the 1500 mg group, a change from baseline of -0.02%, +0.07%, and +0.29%, respectively. The change from baseline did not differ for the 1000 mg group versus placebo, but was significantly different in the 1500 mg group versus placebo (p=0.048).

Fasting blood glucose levels in both niacin groups were increased from baseline at weeks 4 and 8, but did not differ from baseline at week 16. The return to levels similar to baseline may have been due to an increase in the percentage of patients in the 1500 mg group who had adjustments in their antidiabetic medication.

Four patients discontinued participation because of inadequate glucose control. Study drug-related adverse event did not differ between treatment groups (39% in the placebo group, 44% in the 1000 niacin group, and 44% in the 1500 mg niacin group). Rates of adverse events other than flushing were similar for the niacin and placebo groups. Four patients discontinued participation owing to flushing (three in the niacin groups and one in the placebo group). No patients had liver enzymes elevated >3 times the upper reference limit, and there was no drug-induced myopathy.

Interpretation:

Among diabetic patients with dyslipidemia, treatment with niacin was associated with improvements in lipid parameters compared with placebo, with minor increases in glucose and no indication of an increase in adverse events.

Niacin use had been discouraged in patients with diabetes, due in large part to nonrandomized studies that reported worsening glycemic control in patients treated with niacin. As with the ADMIT trial, glucose levels were elevated in the niacin 1500 mg group, but the increases in glucose did not appear to result in increases in study drug discontinuation. Additionally, by 16 weeks, glucose levels in the present trial were reduced back toward baseline levels, although this appears to be due to adjustments in antidiabetic medication. As with the ADMIT trial, it should be noted that diabetic patients in the present trial had stable, controlled diabetes, and those with uncontrolled diabetics were excluded.

References:

Grundy SM, Vega GL, McGovern ME, et al. Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the assessment of diabetes control and evaluation of the efficacy of niaspan trial. Arch Intern Med 2002;162:1568-76.

Keywords: Insulin, Hyperlipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Diabetes Mellitus, Type 2, Hypercholesterolemia, Cholesterol, Blood Glucose, Liver, Hypolipidemic Agents, Hypoglycemic Agents, Niacin, Muscular Diseases, Triglycerides, Fasting


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