GSE significantly improved markers of inflammation and glycaemia and a sole marker of oxidative stress in obese Type 2 diabetic subjects at high risk of cardiovascular events over a 4-week period, which suggests it may have a therapeutic role in decreasing cardiovascular risk.

Background Progressive β-cell failure is a characteristic feature of type 2 diabetes; consequently, β-cell secretagogues are useful for achieving sufficient glycaemic control. The European GUIDE study is the first large-scale head-to-head comparison of two sulphonylureas designed for once-daily administration used under conditions of everyday clinical practice.Design Eight hundred and forty-five type 2 diabetic patients were randomized to either gliclazide modified release (MR) 30 -120 mg daily or glimepiride 1 -6 mg daily as monotherapy or in combination with their current treatment (metformin or an α-glucosidase inhibitor) according to a double-blind, 27-week, parallel-group design. Efficacy was evaluated by HbA1c and safety by hypoglycaemic episodes using the European Agency definition.Results HbA 1c decreased similarly in both groups from 8·4% to 7·2% on gliclazide MR and from 8·2% to 7·2% on glimepiride. Approximately 50% of the patients achieved HbA1c levels less than 7%, and 25% less than 6·5%. The mean difference between groups of the final HbA 1c was −0·06% (noninferiority test P < 0·0001). No hypoglycaemia requiring external assistance occurred. Hypoglycaemia with blood glucose level < 3 mmol L −1 occurred significantly less frequently (P = 0·003) with gliclazide MR (3·7% of patients) compared with glimepiride (8·9% of patients). The distribution of the sulphonylurea doses was similar in both groups.Conclusions This study provides new insights into therapeutic strategies using sulphonylureas. It shows that gliclazide MR is at least as effective as glimepiride, either as monotherapy or in combination. The safety of gliclazide MR was significantly better, demonstrating approximately 50% fewer confirmed hypoglycaemic episodes in comparison with glimepiride.

No abstract

After pretreatment with the selective monoamine oxidase B inhibitor, (-)-deprenyl, in doses sufficient for complete inhibition of the platelet enzyme, 4 normal and 6 parkinsoniam volunteers (2 receiving levodopa and 2 levodopa plus carbidopa) suffered no adverse pressor reaction ('cheese effect') after challenge with oral tyramine in amounts considerably greater than those likely to be encountered in a normal diet. Nor did the levodopa-deprenyl combination itself result in a pressor response. Normal human intestinal mucosa was shown predominantly to contain the deprenyl-insensitive A form of the enzyme, which presumably degraded administered tyramine in the deprenyl-treated volunteers; even those receiving the drug for prolonged periods manifested no 'cheese effect', suggesting that the A form remained uninhibited. Intestinal monoamine oxidase A was able to oxidise dopamine, whereas in human platelet or striatum the amine is a monoamine oxidase B substrate. Like tyramine, oral phenylethylamine challenge with amounts greater than those known to be present in a normal diet similarly gave rise to no adverse reaction in (-)-deprenyl-treated subjects; the reasons for this remain to be determined.