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Clinical bottom line

Statin therapy can significantly reduce morbidity and mortality in diabetics. The decision to treat should be based on vascular risk and not initial cholesterol levels.



About 150 million people have diabetes worldwide, and that the prevalence may double by 2025. Diabetics are at increased risk of cardiovascular morbidity and mortality, but as a group have not been targeted for lipid-lowering therapy, probably because their serum concentrations of total and LDL cholesterol are similar to those in the general population, although triglycerides may be raised and HDL cholesterol lowered in type 2 diabetes, and in type 1 diabetes with poor glycemic control.

Observational studies have shown a direct association between stable/maintained total cholesterol levels and coronary heart disease rates, which is independent of baseline cholesterol level. The Multiple Risk Factor Intervention Trial [1] screened 360,000 middle-aged American men, and found that a 1.0 mmol/L lower level is associated with a 50% lower coronary disease risk. For the 5,000 diabetics included in the study, the absolute risk of coronary mortality was three to five times higher than for non-diabetics for each level of total cholesterol.

A meta-analysis of seven trials of cholesterol-lowering agents (mostly statins) found that treatment for about 5 years resulted in a 25% (95% CI 7-39) reduction in the combined outcome of coronary heart disease death and non-fatal myocardial infarction [2]. Individual cardiovascular outcomes showed the same trend, but with wide confidence intervals, and were not statistically significant. Only 2,603 diabetics were included in these trials, representing 8% of the total trial population (2-25% in individual trials), so it is not surprising that numbers were too low to show significant differences.

A recently published analysis of results from the MRC/BHF Heart Protection Study has clearly demonstrated the benefits of statin use in diabetics [3]. 5,963 adult diabetics (of whom about 2,000 had pre-existing coronary disease, 1,000 had other occlusive arterial disease, and 3,000 had no evidence of occlusive arterial disease) and 14,573 adults with arterial occlusive disease but no diabetes, were randomised to simvastatin (40 mg/day) or placebo, for five years. Changes in lipid profiles during treatment were substantial, and similar in diabetic and non diabetic patients.

Table 1: Changes in lipid profile during treatment with simvastatin (40 mg/day for five years), compared to placebo, in diabetics and non-diabetics.

Diabetes (n=5,963) No diabetes (n=14,573)
Baseline (mmol/L) Mean change (mmol/L) Baseline (mmol/L) Mean change (mmol/L)
Total cholesterol 5.7 -1.1 5.9 -1.2
LDL cholesterol 3.2 -0.9 3.4 -1
HDL cholesterol 1.06 0.01 1.06 0.04
Triglycerides 2.3 -0.3 2 -0.3
Baseline values are mean values

The rate for the combined outcome of any major vascular event was reduced by about a quarter, and this rate was similar for the individual outcomes of any major coronary event, stroke, and revascularisations. Importantly, the proportional risk reduction did not differ between diabetics and non-diabetics, or for various subgroups of diabetic patient based on duration, type or control of diabetes, sex, age, baseline cholesterol level, or established vascular disease at entry.

Table 2: Main outcome events for diabetic and non-diabetic patients.

Event Simvastatin (n=10,269) Placebo (n=10,267) Absolute Risk Reduction Relative Risk Reduction (95% CI)
Major coronary event
Diabetes 279 (9.4%) 377 (12.6%) 3.2%
No diabetes 619 (8.5%) 835 (11.5%) 3.0%
All patients 898 (8.7%) 1212 (11.8%) 3.1% 27% (21-33)
Diabetes 149 (5.0%) 193 (6.5%) 1.5%
No diabetes 295 (4.0%) 392 (5.4%) 1.4%
All patients 444 (4.3%) 585 (5.7%) 1.4% 25% (15-34)
Diabetes 260 (8.7%) 309 (10.4%) 1.7%
No diabetes 679 (9.3%) 896 (12.3%) 3.0%
All patients 939 (9.1%) 1205 (11.7%) 2.6% 24% (17-30)
All major vascular events
Diabetes 601 (20.2%) 748 (25.1%) 4.9%
No diabetes 1432 (19.6%) 1837 (25.2%) 5.6%
All patients 2033 (19.8%) 2585 (25.2%) 5.4% 24% (19-28)

We might expect to see larger absolute risk reductions for diabetics since they have higher baseline risk levels than non-diabetics matched for age, cardiovascular disease and cholesterol. However, in this study the non-diabetics were generally older and more likely to have a history of occlusive arterial disease, which would account for the similar absolute risk reductions seen here.

After corrections for non-compliance in the study, the authors estimate that treatment of diabetics without established occlusive arterial disease with 40 mg/day of simvastatin for five years would prevent about 45 people per 1,000 from having one or more major vascular events (about 70 events in total). For diabetics with established occlusive arterial disease, about 90 people per 1,000 would benefit.

Treatment did not have any effect on glycaemic control or the incidence of newly diagnosed diabetes, and elevations of liver and muscle enzymes were rare and did not differ between treated and placebo groups. There may have been small beneficial effects on peripheral macrovascular complications and renal function.


Statin therapy can significantly reduce morbidity and mortality in diabetics. The decision to treat should be based on vascular risk and not initial cholesterol levels.


J Stamler et al. Diabetes, other risk factors and 12-year cardiovascular mortality for men screened in the multiple factor intervention trial. Diabetes Care 1993 16:434-444.
ES Huang et al. The effect of interventions to prevent cardiovascular disease in patients with type 2 diabetes mellitus. Am J Med 2001 111: 633-642.
MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003 361: 2005-2016.

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