For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
87
views
11
references
 Top references
cited by
27
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      757
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references11

          • Record: found
          • Abstract: found
          • Article: not found

          Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.

          Jan Bolinder, Östen Ljunggren, Joel Kullberg … (2012)
          Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion, and weight loss is a consistent associated finding. Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components. This was a 24-wk, international, multicenter, randomized, parallel-group, double-blind, placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries. Included were 182 patients with T2DM (mean values: women 63.3 and men 58.6 yr of age; hemoglobin A1c 7.17%, body mass index 31.9 kg/m2, and body weight 91.5 kg) inadequately controlled on metformin. Dapagliflozin 10 mg/d or placebo was added to open-label metformin for 24 wk. Primary endpoint was total body weight (TBW) change from baseline at wk 24. Key secondary endpoints were waist circumference and dual-energy x-ray absorptiometry total-body fat mass (FM) changes from baseline at wk 24, and patient proportion achieving body weight reduction of at least 5% at wk 24. In a subset of patients, magnetic resonance assessment of visceral adipose tissue (VAT) and sc adipose tissue (SAT) volume and hepatic lipid content were also evaluated. At wk 24, placebo-corrected changes with dapagliflozin were as follows: TBW, -2.08 kg [95% confidence interval (CI)=-2.84 to -1.31; P<0.0001]; waist circumference, -1.52 cm (95% CI=-2.74 to -0.31; P=0.0143); FM, -1.48 kg (95% CI=-2.22 to -0.74; P=0.0001); proportion of patients achieving weight reduction of at least 5%, +26.2% (95% CI=15.5 to 36.7; P<0.0001); VAT, -258.4 cm3 (95% CI=-448.1 to -68.6; nominal P=0.0084); SAT, -184.9 cm3 (95% CI=-359.7 to -10.1; nominal P=0.0385). In the dapagliflozin vs. placebo groups, respectively, serious adverse events were reported in 6.6 vs. 1.1%; events suggestive of vulvovaginitis, balanitis, and related genital infection in 3.3 vs. 0%; and lower urinary tract infections in 6.6 vs. 2.2%. Dapagliflozin reduces TBW, predominantly by reducing FM, VAT and SAT in T2DM inadequately controlled with metformin.
          Article 0 comments Cited 314 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            SGLT2 inhibition--a novel strategy for diabetes treatment.

            Edward Chao, Robert Henry (2010)
            Inhibiting sodium-glucose co-transporters (SGLTs), which have a key role in the reabsorption of glucose in the kidney, has been proposed as a novel therapeutic strategy for diabetes. Genetic mutations in the kidney-specific SGLT2 isoform that result in benign renal glycosuria, as well as preclinical and clinical studies with SGLT2 inhibitors in type 2 diabetes, support the potential of this approach. These investigations indicate that elevating renal glucose excretion by suppressing SGLT2 can reduce plasma glucose levels, as well as decrease weight. Although data from ongoing Phase III trials of these agents are needed to more fully assess safety, results suggest that the beneficial effects of SGLT2 inhibition might be achieved without exerting significant side effects--an advantage over many current diabetes medications. This article discusses the role of SGLT2 in glucose homeostasis and the evidence available so far on the therapeutic potential of blocking these transporters in the treatment of diabetes.
            Article 0 comments Cited 199 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Effects of Dapagliflozin, an SGLT2 Inhibitor, on HbA1c, Body Weight, and Hypoglycemia Risk in Patients With Type 2 Diabetes Inadequately Controlled on Pioglitazone Monotherapy

              Julio Rosenstock, Marisa Vico, Li-li Wei … (2012)
              OBJECTIVE To examine the safety and efficacy of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, added on to pioglitazone in type 2 diabetes inadequately controlled on pioglitazone. RESEARCH DESIGN AND METHODS Treatment-naive patients or those receiving metformin, sulfonylurea, or thiazolidinedione entered a 10-week pioglitazone dose-optimization period with only pioglitazone. They were then randomized, along with patients previously receiving pioglitazone ≥30 mg, to 48 weeks of double-blind dapagliflozin 5 (n = 141) or 10 mg (n = 140) or placebo (n = 139) every day plus open-label pioglitazone. The primary objective compared HbA1c change from baseline with dapagliflozin plus pioglitazone versus placebo plus pioglitazone at week 24. Primary analysis was based on ANCOVA model using last observation carried forward; all remaining analyses used repeated-measures analysis. RESULTS At week 24, the mean reduction from baseline in HbA1c was −0.42% for placebo versus −0.82 and −0.97% for dapagliflozin 5 and 10 mg groups, respectively (P = 0.0007 and P < 0.0001 versus placebo). Patients receiving pioglitazone alone had greater weight gain (3 kg) than those receiving dapagliflozin plus pioglitazone (0.7–1.4 kg) at week 48. Through 48 weeks: hypoglycemia was rare; more events suggestive of genital infection were reported with dapagliflozin (8.6–9.2%) than placebo (2.9%); events suggestive of urinary tract infection showed no clear drug effect (5.0–8.5% for dapagliflozin and 7.9% for placebo); dapagliflozin plus pioglitazone groups had less edema (2.1–4.3%) compared with placebo plus pioglitazone (6.5%); and congestive heart failure and fractures were rare. CONCLUSIONS In patients with type 2 diabetes inadequately controlled on pioglitazone, the addition of dapagliflozin further reduced HbA1c levels and mitigated the pioglitazone-related weight gain without increasing hypoglycemia risk.
              Article 0 comments Cited 130 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): BMJ Open
                Journal ID (iso-abbrev): BMJ Open
                Journal ID (hwp): bmjopen
                Journal ID (publisher-id): bmjopen
                Title: BMJ Open
                Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                ISSN (Electronic): 2044-6055
                Publication date Collection: 2014
                Publication date (Electronic): 5 April 2014
                Volume: 4
                Issue: 4
                Electronic Location Identifier: e004619
                Affiliations
                [1 ]State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macao, China
                [2 ]School of Informatics, University of Edinburgh , Edinburgh, Scotland, UK
                Author notes
                [Correspondence to ] Siu-wai Leung; siu@ 123456inf.ed.ac.uk

                YS and YZ are joint first authors.

                Article
                Publisher ID: bmjopen-2013-004619
                DOI: 10.1136/bmjopen-2013-004619
                PMC ID: 3987716
                PubMed ID: 24710132
                SO-VID: ab8e8315-5ef6-429e-aeab-079e6ac3235e
                Copyright © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions
                License:

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

                History
                Date received : 4 December 2013
                Date revision received : 14 March 2014
                Date accepted : 17 March 2014
                Categories
                Subject: Evidence Based Practice
                Subject: Research
                Subject: 1506
                Subject: 1694
                Subject: 1843
                Subject: 1694

                ScienceOpen disciplines: Medicine
                Keywords: dapagliflozin,type 2 diabetes mellitus,meta-analysis
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: dapagliflozin, type 2 diabetes mellitus, meta-analysis

                Comments

                Comment on this article

                scite_

                Similar content757

                See all similar

                Cited by26

                See all cited by

                Most referenced authors910

                See all reference authors