BackgroundDespite the number of medications for type 2 diabetes, many people with the condition do not achieve good glycaemic control. Some existing glucose-lowering agents have adverse effects such as weight gain or hypoglycaemia. Type 2 diabetes tends to be a progressive disease, and most patients require treatment with combinations of glucose-lowering agents. The sodium glucose co-transporter 2 (SGLT2) receptor inhibitors are a new class of glucose-lowering agents.ObjectiveTo assess the clinical effectiveness and safety of the SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes.Data sourcesMEDLINE, Embase, Cochrane Library (all sections); Science Citation Index; trial registries; conference abstracts; drug regulatory authorities; bibliographies of retrieved papers.Inclusion criteriaRandomised controlled trials of SGLT2 receptor inhibitors compared with placebo or active comparator in type 2 diabetes in dual or combination therapy.MethodsSystematic review. Quality assessment used the Cochrane risk of bias score.ResultsSeven trials, published in full, assessed dapagliflozin and one assessed canagliflozin. Trial quality appeared good. Dapagliflozin 10 mg reduced HbA1c by −0.54% (weighted mean differences (WMD), 95% CI −0.67 to −0.40) compared to placebo, but there was no difference compared to glipizide. Canagliflozin reduced HbA1c slightly more than sitagliptin (up to −0.21% vs sitagliptin). Both dapagliflozin and canagliflozin led to weight loss (dapagliflozin WMD −1.81 kg (95% CI −2.04 to −1.57), canagliflozin up to −2.3 kg compared to placebo).LimitationsLong-term trial extensions suggested that effects were maintained over time. Data on canagliflozin are currently available from only one paper. Costs of the drugs are not known so cost-effectiveness cannot be assessed. More data on safety are needed, with the Food and Drug Administration having concerns about breast and bladder cancers.ConclusionsDapagliflozin appears effective in reducing HbA1c and weight in type 2 diabetes, although more safety data are needed.

We use the Dijkgraaf-Vafa technique to study massive vacua of 6D SU(N) SYM theories on tori with R-symmetry twists. One finds a matrix model living on the compactification torus with a genus 2 spectral curve. The Jacobian of this curve is closely related to a twisted four torus T in which the Seiberg-Witten curves of the theory are embedded. We also analyze R-symmetry twists in a bundle with nontrivial first Chern class which yields intrinsically 6D SUSY breaking and a novel matrix integral whose eigenvalues float in a sea of background charge. Next we analyze the underlying integrable system of the theory, whose phase space we show to be a system of N-1 points on T . We write down an explicit set of Poisson commuting Hamiltonians for this system for arbitrary N and use them to prove that equilibrium configurations with respect to all Hamiltonians correspond to points in moduli space where the Seiberg-Witten curve maximally degenerates to genus 2, thereby recovering the matrix model spectral curve. We also write down a conjecture for a dual set of Poisson commuting variables which could shed light on a particle-like interpretation of the system.