Based on the CTT meta-analysis [13], in adults who have diabetes, it was estimated that a low-potency statin would prevent approximately 45 patients per 1,000 from having a major vascular event over five years. Given that high-potency statins are roughly two and one-half times as effective as low potency ones, a high-potency statin prevents approximately 113 patients per 1,000 from having a major vascular event over 5 years with a number needed to treat (NNT) of 9. This is approximately half the 5-year number needed to treat of 20 for a major vascular event found in the Justification for the Use of statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial [14], a primary prevention trial of a potent statin, rosuvastatin 20 mg daily, that excluded diabetic patients. Economic analyses of randomized trials, including the HPS [15], have shown statin therapy is cost-effective, if not cost saving, for a wide range of diabetic patients.

In the Steno-2 study, investigators from Denmark randomly assigned 160 patients with type 2 diabetes and microalbuminuria to a multifactorial intervention (lipid-lowering therapy, aspirin, renin-angiotensin inhibition, and tight glucose control) versus conventional therapy [16]. The study completed follow-up in 2006 after a mean duration of treatment of 7.8 years and additional mean observation period of 5.5 years. During the intervention phase, 85 % of the treatment group took statins (mean attained LDL-C 83 mg/dL from 133 mg/dL at baseline) compared with 22 % of the conventional therapy group (mean attained LDL-C 126 mg/dL from 137 mg/dL at baseline). More than eight in ten patients in both groups went on to take statins in the observation phase with mean LDL-C concentrations converging near 70 mg/dL; however, survival curves continued to diverge.

Upon completion of follow-up, compared with 40 deaths in the conventional therapy group, only 24 patients who received multifactorial intervention died (hazard ratio 0.54 [95 % CI 0.32–0.89], p = 0.02). Multifactorial intervention reduced cardiovascular mortality (hazard ratio 0.43 [95 % CI 0.19–0.94], p = 0.04) and cardiovascular events (hazard ratio 0.41 [95 % CI 0.25–0.67], p < 0.001). Even with imperfect implementation (proportion of patients achieving ideal treatment targets was modest), the NNTs over the full study period (7.8 years of intervention and an additional 5.5 years of follow-up) were impressively low: three patients to prevent one cardiovascular event, five patients to prevent death from any cause, and eight patients to prevent a cardiovascular death. It was concluded that statins and antihypertensive therapies were the two most influential therapies in reducing risk. In sum, Steno-2 demonstrates that early implementation of statin therapy as part of a multifaceted approach to risk reduction achieves dramatic reductions in absolute risk, and thus low numbers needed to treat, making primary prevention strategies incorporating statin therapy in diabetic patients second to few if any other medical therapies in modern medicine.