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Summary: Objectives: The objective of the study is to compare the efficacy of hypoglycaemic drugs for type 2 diabetes mellitus (T2DM) by network meta‐analysis of randomized controlled trials (RCTs). Methods: We compared 11 major oral hypoglycaemic drugs under five categories evaluated by RCTs as drug monotherapy for the patients with T2DM, measuring glycosylated haemoglobin (%) or fasting plasma glucose (mmol L−1) as outcomes. RCT quality was assessed with the Cochrane risk of bias tool. Network meta‐analysis estimated the mean differences and 95% credible intervals. Subgroup and sensitivity analyses were performed to determine the results robustness. The Grading of Recommendation, Assessment, Development, and Evaluation evidence strength was assessed. Results: Seventy‐five RCTs including 33,830 patients were identified. Their study quality was high. Regarding glycosylated haemoglobin, top three anti‐diabetics were repaglinide (mean differences −1.39 [95% credible intervals −1.75 to −1.03]), gliclazide (−1.37 [−2.04 to −0.71]) and metformin (−1.13 [−1.37 to −0.90]), against placebo. Regarding fasting plasma glucose, top three anti‐diabetics were repaglinide (−2.01 [−2.75 to −0.97]), metformin (−1.72 [−2.16 to −1.27]) and glipizide (−1.57 [−2.44 to −0.64]), against placebo. There was no difference between metformin and repaglinide. Subgroup and sensitivity analyses found the results to be robust. The evidence strength was moderate to high. Conclusion: This meta‐analysis showed that repaglinide and metformin would be the most efficacious oral drugs for first‐line monotherapy of T2DM. [ABSTRACT FROM AUTHOR]

Background and Purpose Kaempferol, a plant flavonoid present in normal human diet, can modulate vasomotor tone. The present study aimed to elucidate the signalling pathway through which this flavonoid enhanced relaxation of vascular smooth muscle. Experimental Approach The effect of kaempferol on the relaxation of porcine coronary arteries to endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) relaxing agents was studied in an in vitro organ chamber setup. The whole-cell patch-clamp technique was used to determine the effect of kaempferol on potassium channels in porcine coronary artery smooth muscle cells ( PCASMCs). Key Results At a concentration without direct effect on vascular tone, kaempferol (3 × 10−6 M) enhanced relaxations produced by bradykinin and sodium nitroprusside. The potentiation by kaempferol of the bradykinin-induced relaxation was not affected by Nω-nitro- L-arginine methyl ester, an inhibitor of NO synthase (10−4 M) or TRAM-34 plus UCL 1684, inhibitors of intermediate- and small-conductance calcium-activated potassium channels, respectively (10−6 M each), but was abolished by tetraethylammonium chloride, a non-selective inhibitor of calcium-activated potassium channels (10−3 M), and iberiotoxin, a selective inhibitor of large-conductance calcium-activated potassium channel ( KCa1.1; 10−7 M). Iberiotoxin also inhibited the potentiation by kaempferol of sodium nitroprusside-induced relaxations. Kaempferol stimulated an outward-rectifying current in PCASMCs, which was abolished by iberiotoxin. Conclusions and Implications The present results suggest that, in smooth muscle cells of the porcine coronary artery, kaempferol enhanced relaxations caused by endothelium-derived and exogenous NO as well as those due to endothelium-dependent hyperpolarization. This vascular effect of kaempferol involved the activation of KCa1.1 channels. [ABSTRACT FROM AUTHOR]