Multifactorial intervention improves outcomes in T2DM (Steno-2)

Clinical Question

Does an intensive multifactorial intervention improve long-term outcomes for patients with type 2 diabetes?

Bottom Line

For high-risk diabetic patients with microalbuminuria, an intensive intervention that includes an angiotensin-converting enzyme inhibitor (ACEI), lipid lowering, aspirin, and tight blood sugar control improves outcomes compared with usual care. It is not clear which specific elements were responsible for the benefit. Based on trials of individual risk factors, the authors conclude that the bulk of the response was related to use of the statin and ACEI, but the greater use of metformin could also have contributed. (LOE = 1b)


Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 2008;358(6):580-591.  [PMID:18256393]

Study Design

Randomized controlled trial (nonblinded)






Outpatient (any)


The original Steno-2 Study identified 160 white Danish patients with type 2 diabetes mellitus and persistent microalbuminuria and randomized them to receive intensive therapy or conventional therapy. Intensive therapy consisted of glycosylated hemoglobin levels <= 6.5%, total cholesterol levels < 175 mg/dL (4.5 mmol/L), serum triglyceride levels < 150 mg/dL (1.7 mmol/L), blood pressure < 130/80 mm Hg, aspirin, and an ACEI regardless of initial blood pressure. Treatment targets for the conventional therapy group are not described. At the end of the intervention study those patients in the intensive therapy group were more likely to be taking an ACEI (97% vs 70%), aspirin (87% vs 56%), metformin (50% vs 34%), or a statin (85% vs 22%). They also had lower blood pressure (15/5 mm Hg). This initial intervention study had a mean follow-up of 7.8 years. It was followed by an additional 5.5 years of follow-up during which the patients' care was managed by their primary physician. At the end of the complete follow-up period many of the differences in management had disappeared; after 13.3 years, there was no difference in the likelihood that patients were taking aspirin, a statin, or an ACEI. At the end of the 13.3-year study period, patients originally assigned to intensive therapy were less likely to have died (30% vs 50%; number needed to treat = 5), primarily because of fewer cardiovascular events. Patients in the intensive therapy group were also less likely to progress to dialysis (1 patient vs 6 patients; P = .04).