ObjectivesThis meta-analysis aimed to evaluate whether dapagliflozin is synergistic with other antidiabetic drugs without body weight gain.SettingRandomised controlled trial (RCT) reports were retrieved from PubMed, Cochrane Library, EMBASE, ClinicalTrials.gov, Google Scholar and Google. Eligible RCTs were selected according to the criteria (including types of participants, intervention, outcomes) and assessed by the Cochrane risk of bias tool and GRADEpro software for evidential quality. Meta-analysis on the eligible RCTs was performed with the random effects model. The RCTs of low-quality and interim stages were excluded for further sensitivity analysis. Meta-regression was conducted on the follow-up durations. Publication bias was evaluated with funnel plots and the Egger's regression test and adjusted using the trim-and-fill procedure. Heterogeneity was assessed with the I2 statistics.ParticipantsAdult patients with type 2 diabetes mellitus (T2DM).InterventionsDapagliflozin combined with conventional antidiabetic drugs.Primary and secondary outcome measuresGlycaemic level (measured by glycosylated haemoglobin (HbA1c) and fasting plasma glucose (FPG)) and body weight.Results12 RCTs were eligible for quantitative synthesis and meta-analysis. The overall effect size of HbA1c calculated from mean difference was −0.52% (Z=−13.56, p<0.001) with 95% CI (−0.60 to −0.45). The effect size of FPG was −1.13 mmol/L (Z=−11.12, p<0.001) with 95% CI (−1.33 to −0.93). The effect size of body weight was −2.10 kg (Z=−18.77, p<0.001) with 95% CI (−2.32 to −1.88). Exclusions of low quality and interim RCTs changed the overall mean differences respectively to −0.56%, −1.11 mmol/L, 2.23 kg and −0.50%, −1.08 mmol/L, −2.08 kg. The sensitivity analysis indicated good robustness of the meta-analysis on HbA1c, FPG and body weight.ConclusionsThe meta-analysis showed that dapagliflozin as an add-on drug to conventional antidiabetic drugs improved the glycaemic control in T2DM participants without significant body weight gain.Trial registration numberCRD42013005034.

Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase, and its dysregulation can lead to ageing, diabetes, and cancer. From 346 experimentally confirmed SIRT1 inhibitors, an inhibitor structure pattern was generated by inductive logic programming (ILP) with DMax Chemistry Assistant software. The pattern contained amide, amine, and hetero-aromatic five-membered rings, each of which had a hetero-atom and an unsubstituted atom at a distance of 2. According to this pattern, a ligand-based virtual screening of 1 444 880 active compounds from Chinese herbs identified 12 compounds as inhibitors of SIRT1. Three compounds (ZINC08790006, ZINC08792229, and ZINC08792355) had high affinity (−7.3, −7.8, and −8.6 kcal/mol, respectively) for SIRT1 as estimated by molecular docking software AutoDock Vina. This study demonstrated a use of ILP and background knowledge in machine learning to facilitate virtual screening.

BackgroundDapagliflozin is a first-in-class oral sodium glucose co-transporter 2 (SGLT2) inhibitor. It is often used in combination with conventional anti-diabetic drugs such as metformin, glimepiride, and insulin in treating type 2 diabetes (T2D). It not only reduces glucose reabsorption in the kidney but also increases renal glucose excretion. Some studies found the actions of dapagliflozin independent of insulin and free from risk of weight gain. This meta-analysis aims to evaluate whether dapagliflozin is synergistic with other anti-diabetic drugs without risk of weight gain.Methods/DesignThis meta-analysis will include the randomized controlled trials (RCT) evaluating the efficacy of dapagliflozin as an add-on drug in treating T2D for >8 weeks with the outcome measures glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG) and body weight. Information of relevant RCTs will be retrieved from major databases including PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and Google Scholar according to a pre-specified search strategy. Google and manual search will find other unpublished reports and supplementary data. Eligible RCTs will be selected according to pre-specified inclusion and exclusion criteria. Data will be extracted and input into a pre-formatted spreadsheet. The Cochrane risk of bias tool will be used to assess the quality of the eligible RCTs. Meta-analysis based on the random-effects model will be conducted to compare the changes of HbA1c (%), FPG (mmol/L), and body weight (kg) between dapagliflozin arm and placebo arm. Publication bias will be evaluated with a funnel plot and the Egger’s test. Heterogeneity will be assessed with the I2 statistics. Sensitivity analysis will be conducted on follow-up periods. The evidential quality of the findings will be assessed with the GRADE profiler.DiscussionThe findings of this meta-analysis will be important to clinicians, patients, and health policy-makers regarding the use of dapagliflozin in T2D treatment.Study registrationPROSPERO registration number: CRD42013005034

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