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Implications for Choice of Glucose-lowering Agents in Type 2 Diabetes
In examining the effect of currently approved glucose-lowering drugs on established CVRFs and, where available, on CV mortality and morbidity, two preliminary considerations are important. First, micro- and macrovascular T2DM complications often coexist in the same patient but have partially different pathophysiology and risk factors. Also, the dose–response relation of hyperglycaemia to microvascular complications is significantly steeper than to macrovascular disease. Secondly, the vast majority of epidemiologic studies and clinical trials is based on major adverse cardiac events (MACE) as the outcome, which includes CV death, non-fatal MI, and non-fatal stroke (sometimes, also unstable angina requiring hospitalization, amputation, and revascularization procedures are included). These outcomes, however, represent the tip of the iceberg of a gamut of manifestations of CVD (Figure 2) including the most common cardiac problem in T2DM, i.e. heart failure, and chronic kidney disease, a potent CVD predictor. Therefore, while MACE is a practical and well-established 'hard' endpoint, its ability to track the natural history of CVD is limited. Finally, although T2DM confers an equivalent risk to ageing 15 years, the beneficial effects of improved glycaemic control on CVD prevention may require >10 years to become manifest. Therefore, prevention of CVD in T2DM patients demands a multifactorial approach to improve/normalize glycaemia and correct multiple the CVRFs, as shown in the survey by Anselmino et al. and prospectively implemented in the Steno-2 Study.
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Figure 2.
Major adverse cardiac events and other major adverse cardiovascular events are the tip of the iceberg of atherosclerotic cardiovascular disease. ABI, ankle-brachial index.
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