Diabetes, obesity & metabolism
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Diabetes Obes Metab · Jan 2012
ReviewTreating diabetes today with gliclazide MR: a matter of numbers.
Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by worsening hyperglycaemia. Lowering haemoglobin A1c to below or around 7% has been shown to reduce microvascular and neuropathic complications of diabetes. The ongoing uncertainty regarding whether intensive glycaemic control can reduce the increased risk of cardiovascular disease (CVD) in people with T2DM stirred the launch of the recent long-term megatrials. ⋯ Several studies showed that gliclazide has antioxidant properties, reduces markers of endothelial inflammation, and prevents glucose-induced apoptosis of endothelial cells. These positive antioxidant effects are not confined to the vascular wall but they are effective also in the β cells. These properties are important because (i) in patients with atherosclerotic process, microvascular abnormalities may hasten disease progression and (ii) slowing the microvascular complications may have a potentially remarkable effect on the natural history of macrovascular disease.
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Most recent meta-analyses of morbidity-mortality risk hazards brought about by the presence of diabetes as compared with non-diabetics underline the dominant risk of renal disease and cardiovascular outcomes and the relevance of blood glucose, blood pressure (BP) and cholesterol levels. The translation of this reality into therapeutic guidelines always requires interventional evidence. Evidence for combined approaches in controlling for BP and blood glucose was provided by Action in Diabetes and Vascular disease: PreterAx and DiamicroN-MR Controlled Evaluation (ADVANCE), conducted in over 11 000 subjects from 20 countries. ⋯ The divergence for other outcomes underlines the importance of considering specific therapeutic approaches for glucose control and prudent targets for BP. The current target values for glycated haemoglobin of 6.5-7% and for BP of 130/80 mmHg appear safe and beneficial. The potential long-term benefit, particularly that of initial tight blood glucose control, suggested by recent post-trial evidence is currently being evaluated in the ADVANCE-ON study.
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Diabetes Obes Metab · Jan 2012
Efficacy and safety of dalcetrapib in type 2 diabetes mellitus and/or metabolic syndrome patients, at high cardiovascular disease risk.
Mixed dyslipidaemia, characterized by low levels of high-density lipoprotein cholesterol (HDL-C) and high levels of triglycerides, is common in patients with type 2 diabetes mellitus (T2DM) and/or metabolic syndrome. Dalcetrapib effectively increases HDL-C levels by modulating cholesteryl ester transfer protein (CETP) activity. The aim of this analysis was to investigate the lipid modifying efficacy and safety of dalcetrapib in patients with T2DM and/or metabolic syndrome. ⋯ Dalcetrapib similarly decreased CETP activity and increased HDL-C levels in patients with and without T2DM or metabolic syndrome; the ongoing Phase III dal-OUTCOMES study will help to determine if dalcetrapib's improvement in lipid levels also reduces cardiovascular morbidity and mortality.