Steno-2 study in type 2 diabetes (with microalbuminuria)

The concept of a polypill in diabetes is supported by the Steno-2 study in which multiple risk factors were targetted and resulted in the intervention group having a signicant reduction in incidence of cardiovascular disease (1)

• study involved 160 high-risk type 2 diabetic patients with microalbuminuria aged 55.1 years (average), who were randomly assigned to a conventional or an intensive, multifactorial intervention for a period of 7.8 years
  • in the intensive group, a stepwise treatment plan was adopted involving both continuous lifestyle education and motivation and an ambitious goal-oriented pharmacological treatment of known modifiable risk factors
    • patients were to follow a reduced-fat diet and exercise regularly, offered smoking cessation counseling, prescribed an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II–receptor blockers (ARB) regardless of blood pressure, and received vitamin supplementation and aspirin
      • stepwise antiglycaemic and antihypertension medications were also prescribed as well as lipid-modifying therapy with a statin and/or fibrate
      • subjects receiving intensive therapy were much more likely to reach their total cholesterol goal (<175 mg/dl (4.5 mmol/l)) and systolic blood pressure goal (<130 mm Hg) and to routinely use angiotensin-converting enzyme (ACE) inhibitors or angiotensin II–receptor blockers (ARBs)
  • the conventional group was treated in accordance with national guidelines for type 2 diabetes with less stringent goals
  • results revealed:
    • in the intensive treatment group: lower systolic and diastolic blood pressures, hemoglobin A(1c) (HbA(1c)), fasting serum total and low-density lipoprotein (LDL) cholesterol, fasting serum triglycerides, and 24-hour urine albumin excretion, as well as increased carbohydrate and decreased fat intake as percentage of total energy
    • there was no difference in weight gain between groups during follow-up and no other major side effects were reported
    • the primary end point was a macrovascular outcome: a composite of death from cardiovascular causes, nonfatal myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, nonfatal stroke, amputation for ischemia, or vascular surgery for peripheral arterial atherosclerosis
    • the differences between groups in surrogate end points translated into the following significant group differences in final clinical end points:
      • 44% of patients in the conventional group had a cardiovascular event compared with 24% in the intensive group, ie, a relative risk reduction of about 50%
      • the relative risk of nephropathy, retinopathy, and autonomic neuropathy (secondary end points) was diminished by about 60% in the intensively treated group
  • the study authors concluded that, an intensified and goal-oriented multipronged approach to the treatment of type 2 diabetes reduces cardiovascular events, as well as nephropathy, retinopathy, and autonomic neuropathy, by about half

Reference:

1. Metabolism. 2003 Aug;52(8 Suppl 1):19-23.