The efficacy of dapagliflozin combined with hypoglycaemic drugs in treating type 2 diabetes mellitus: meta-analysis of randomised controlled trials.

Objectives: This meta-analysis aimed to evaluate whether dapagliflozin is synergistic with other antidiabetic drugs without body weight gain.

Setting: Randomised 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 I(2) statistics.

Participants: Adult patients with type 2 diabetes mellitus (T2DM).

Interventions: Dapagliflozin combined with conventional antidiabetic drugs.

Primary And Secondary Outcome Measures: Glycaemic level (measured by glycosylated haemoglobin (HbA1c) and fasting plasma glucose (FPG)) and body weight.

Results: 12 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.

Conclusions: The 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 Number: CRD42013005034.