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

Abstract

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.

Changes in HbA1c, body weight, and systolic blood pressure in type 2 diabetes patients initiating dapagliflozin therapy: a primary care database study

“…In addition, HbA1c reductions were greater in patients with poor glycemic control. These real-world treatment effects are comparable to results of dapagliflozin randomized clinical trials 7–15,18–21,26…”

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

“…A meta-analysis 308 of RCTs of 12-104 weeks duration showed that dapagliflozin (2.5-10.0 mg per day) improved HbA 1c , FPG and weight compared with placebo when used as an add-on therapy to metformin, insulin, thiazolidinediones, sulfonylureas or metformin ± sitagliptin (mean difference between groups −0.52%, 95% CI −0.60% to −0.45%, −1.52 mmol/l, 95% CI −1.75 mmol/l to −1.29 mmol/l and −1.61 kg, 95% CI −1.97 kg to −1.26 kg, respectively). The reductions in HbA 1c and FPG compared with placebo were generally similar with different background treatments, but were greatest when dapagliflozin was added to a sulfonylurea (−0.96%, 95% CI −0.86% to −0.52% and −1.47 mmol/l, 95% CI −1.86 mmol/l to −1.08 mmol/l) 308 . The largest between-group difference in weight change was seen when dapagliflozin was added to insulin (−2.45 kg, 95% CI −2.99 kg to −1.92 kg) 308 .…”

“…The reductions in HbA 1c and FPG compared with placebo were generally similar with different background treatments, but were greatest when dapagliflozin was added to a sulfonylurea (−0.96%, 95% CI −0.86% to −0.52% and −1.47 mmol/l, 95% CI −1.86 mmol/l to −1.08 mmol/l) 308 . The largest between-group difference in weight change was seen when dapagliflozin was added to insulin (−2.45 kg, 95% CI −2.99 kg to −1.92 kg) 308 .…”

Patient Navigators Connecting Patients to Community Resources to Improve Diabetes Outcomes

“…The observed effects of a 0.6% change in HbA 1c were comparable with those reported in meta-analyses and systematic reviews of pharmaceutical agents for treating diabetes and is considered to be clinically significant. 29,30 Self-efficacy has been strongly associated with better adherence to diabetes treatment recommendations and improved patient outcomes. 31 Current evidence suggests that incorporating self-efficacy in health assessment and interventions to increase a person's perceived ability to self-manage is beneficial for improved diabetes care.…”