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Dr Vijay Viswanathan, Chennai 31 January 2018

nondiabetic counterparts.
Guidance for industry - A therapy should demonstrate that it will not result in an unacceptable increase in: CV mortality; myocardial infarction (MI) and stroke; hospitalization for acute coronary syndrome, urgent revascularization procedures; other endpoints. CV safety of modern vs. older SUs: Modern SUs like glimepiride do not inhibit mitochondrial KATP channels in the heart; hence, the protective mechanism of ischemic preconditioning (IPC) is preserved with glimepiride; older SUs inhibit mitochondrial KATP, which further inhibits IPC. The use of 2nd and 3rd generation SUs in patients with type 2 diabetes is not associated with increased CV risk irrespective of comparator or background medication.
SUs as an add-on to metformin have been considered safe in terms of overall and CV mortality. In a recent pragmatic trial, incidence of CV events was similar with SUs and pioglitazone as add-on treatments to metformin. New SUs (glimepiride/gliclazide) may be associated with a lower risk of MI than old SUs (glibenclamide). Modern SUs have fewer early complications and lower mortality than older SUs. Newer SUs, especially glimepiride, may be preferred in patients with underlying CAD.

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