Hyperinsulinemia: the Outcome of its Metabolic Effects - HOME

Description:

The goal of the trial was to evaluate treatment with metformin compared with placebo in patients with type 2 diabetes mellitus.

Hypothesis:

Metformin will produce sustained beneficial metabolic and cardiovascular effects.

Study Design

  • Placebo Controlled
  • Randomized
  • Parallel
  • Blinded

Patients Screened: 745
Patients Enrolled: 390
Mean Follow Up: 4.3 years
Mean Patient Age: 64 years
Female: 59%

Patient Populations:

  • Patients with type 2 diabetes

Primary Endpoints:

  • Aggregate of microvascular and macrovascular morbidity and mortality that includes:
    • Myocardial infarction
    • Heart failure
    • Ischemic ECG changes
    • Acute coronary syndrome
    • Diabetic foot
    • Stroke
    • Transient ischemic attack
    • Peripheral arterial disease
    • Peripheral arterial reconstruction
    • Percutaneous coronary intervention
    • Coronary artery bypass grafting
    • Nontraumatic amputation
    • Sudden death
    • Progression of retinopathy
    • Progression of nephropathy
    • Progression of neuropathy
    • Noncardiovascular sudden death

Secondary Endpoints:

  • HbA1c
  • Insulin requirement
  • Lipid levels
  • Blood pressure
  • Body weight
  • Body mass index

Drug/Procedures Used:

Patients with type 2 diabetes were prerandomized during which time they maintained blood glucose levels between 72 and 126 mg/dl with insulin therapy. After 12 weeks, patients were randomized to 850 mg of metformin (n = 196) versus placebo (n = 194) 1-3 times daily.

Concomitant Medications:

At baseline, the use of antihypertensive medications was 47%, and lipid-lowering medications was 16%.

Principal Findings:

Overall, 390 patients were randomized. In the metformin group, mean age was 64 years, 59% were women, duration of diabetes was 14 years, duration of insulin treatment was 7 years, body mass index was 30 kg/m2, glycated hemoglobin HbA1c level was 7.9%, systolic blood pressure was 160 mm Hg, and low-density lipoprotein cholesterol (LDL-C) was 139 mg/dl.

The occurrence of the primary endpoint, aggregate microvascular and macrovascular complications, was 31% with metformin versus 28% with placebo (adjusted p value = 0.33). Macrovascular complications occurred in 15% versus 18% (adjusted p value = 0.04), and microvascular complications occurred in 17% versus 15% (adjusted p value = 0.43), respectively, for metformin versus placebo.

Secondary outcomes at follow-up: body weight (87 vs. 91 kg), body mass index (30 vs. 31 kg/m2), HbA1c (7.7 vs. 7.9%), systolic blood pressure (141 vs. 141 mm Hg), LDL-C (81 vs. 85), and hypoglycemic events (2.1 vs. 2.6 events), respectively, for metformin versus placebo.

Interpretation:

Among patients with type 2 diabetes, the addition of metformin to insulin therapy appeared to have a modestly beneficial effect on maintaining body weight and improving glycemic control over 4.3 years of follow-up. Hypoglycemic episodes were similar between the groups. Despite the small improvement in glycemic control, there was no difference in the primary outcome, an aggregate of microvascular and macrovascular complications. After adjustment for several baseline characteristics, there was a small improvement in macrovascular complications with metformin. Limitations include the small sample size and the rather unconventional primary outcome that included 17 components.

References:

Kooy A, de Jager J, Lehert P, et al. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Arch Intern Med 2009;169:616-25.

Clinical Topics: Dyslipidemia, Lipid Metabolism, Nonstatins

Keywords: Lipoproteins, LDL, Hemoglobin A, Glycosylated, Cholesterol, Follow-Up Studies, Body Mass Index, Metformin, Diabetes Mellitus, Type 2, Blood Pressure, Hypoglycemic Agents, Insulins


< Back to Listings