Dataset Information

The efficacy of dapagliflozin combined with hypoglycemic drugs in treating type 2 diabetes: protocol for meta-analysis of randomized controlled trials.

ABSTRACT:

Background

Dapagliflozin 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/design

This 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 Google and manual search will find other unpublished reports and supplementary data.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.

Discussion

The findings of this meta-analysis will be important to clinicians, patients, and health policy-makers regarding the use of dapagliflozin in T2D treatment.

Study registration

PROSPERO registration number: CRD42013005034.

SUBMITTER: Sun YN

PROVIDER: S-EPMC3833641 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Publications

The efficacy of dapagliflozin combined with hypoglycemic drugs in treating type 2 diabetes: protocol for meta-analysis of randomized controlled trials.

Sun Yu-Nan YN Zhou Yi Y Chen Xi X Che Wen-Si WS Leung Siu-Wai SW

Systematic reviews 20131113

<h4>Background</h4>Dapagliflozin 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 w ...[more]

PMID: 24225054

Similar Datasets

Project description:AimTo evaluate the effect of an inhibitor of sodium-glucose cotransporter 2 (SGLT-2 inhibitor, dapagliflozin) on glycemic variability in type 2 diabetes mellitus (T2D) under insulin glargine combined with oral hypoglycemic drugs, using a continuous glucose monitoring system (CGMS).MethodsThis prospective, self-controlled, single-center clinical trial recruited 36 patients with T2D under combined insulin glargine and oral hypoglycemic drugs. General clinical data were collected. Fasting blood glucose (FBG), postprandial blood glucose (PBG), glycosylated hemoglobin (HbA1c), and C-peptide levels were assessed before and four weeks of dapagliflozin (10 mg per day) treatment. Blood glucose was monitored for 72 hours before and after treatment using CGMS.ResultsAfter treatment with dapagliflozin, FBG decreased from 6.74 ± 1.78 to 5.95 ± 1.13 mmol/L (p < 0.05); PBG decreased from 13.04 ± 2.99 to 10.92 ± 3.26 mmol/L (p < 0.05); HbA1c decreased from 7.37 ± 0.96% to 6.94 ± 0.80%. The proportion of patients with HbA1c < 7% increased from 27.8% to 58.3%, and the proportion of patients with HbA1c < 7% and without level 2 hypoglycemia increased from 27.8% to 55.6% (p < 0.05). CGMS data showed reduction of the 24 h MBG, MAGE, time-above-range (TAR, >10 mmol/L), high blood glucose index (HBGI), glucose management indicator (GMI), and incremental area under the curve of the glucose level more than 10 mmol/L (AUC > 10) and an increase of time-in-range (TIR, 3.9-10 mmol/L) with treatment. Homeostasis model assessment for pancreatic beta-cell function (HOMA-beta) increased significantly with treatment (p < 0.05), and fewer insulin doses were required after the treatment, without increasing in hypoglycemia and urinary tract infection. Further, a stratified analysis showed that patients with higher pretreatment HbA1c and waist-to-hip ratio (WHR) had greater improvement in glycemic control.ConclusionDapagliflozin may reduce blood glucose levels, ameliorate glycemic variability, and improve pancreatic beta-cell function in patients with T2D under insulin glargine combined with other oral hypoglycemic drugs, especially in those with poor glucose control and abdominal obesity.

Project description:BackgroundDapagliflozin, a novel inhibitor of sodium-glucose cotransporter-2 (SGLT-2), lowers blood glucose level by specifically inhibiting the activity of SGLT-2. Previous studies showed efficacy and safety of dapagliflozin combined with other antihyperglycemic agents in type 2 diabetes (T2DM), however, there are few studies for dapagliflozin as monotherapy. The aim of this study was to assess the efficacy and safety of dapagliflozin as a monotherapy in T2DM and provide theoretical basis for clinical rational use of drugs.MethodsWe did a systematic review and meta-analysis of randomized, placbo-controlled clinical studies in patients with type 2 diabetes. We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP database through October 2018, we also manually screened list of references to the previous meta-analysis of dapagliflozin in the treatment of type 2 diabetes. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. A meta-analysis was conducted by using RevMan 5.3 software.ResultsSix randomized controlled trials (RCTs) including 2033 patients were analyzed. Compared with placebo, dapagliflozin monotherapy was associated with a reduction in glycosylated hemoglobin A1c (HbA1c) (weighted mean difference [WMD]: -0.60%; 95% confidence interval [CI]: -0.67%, -0.52%; P < .00001), fasting plasam glucose (FPG) (WMD: -1.30 mmol/L; 95% CI: -1.52, -1.08; P < .00001), and body weight (WMD: -1.50 kg; 95% CI: -1.67, -1.32; P < .00001). Dapagliflozin was associated with an increased risk of urinary tract infections (relative risk [RR]: 1.74; 95% CI: 1.21, 2.49; P = .003) and genital tract infections (RR: 3.52; 95% CI: 2.06, 6.03; P < .00001).ConclusionsDapagliflozin monotherapy was well tolerated and effective in reducing the level of HbA1c, FPG, and body weight in patients with T2DM without increasing hypoglycaemia, although it may increase the risk of urinary tract infections and genital tract infections. This meta-analysis provides an evidence for the treatment in patients with T2DM. However, more randomized clinical evidences are still needed to verify the results.

Project description:The safety and efficacy of different drugs in treatment of gestational diabetes mellitus (GDM) patients who could not maintain normal glucose level only through diet and exercise remains to be debated. We performed this network meta-analysis (NAM) to compare and rank different antidiabetic drugs in glucose level control and pregnancy outcomes in GDM patients.We searched PubMed, Cochrane Library, Web of Science, and Embase up to December 31, 2016. Randomized controlled trials (RCTs) related to different drugs in the treatment of GDM patients were enrolled. We extracted the relevant information and assessed the risk of bias with the Cochrane risk of bias tool. We did pair-wise meta-analyses using the fixed-effects model or random-effects model and then adopted random-effects NAM combining both direct and indirect evidence within a Bayesian framework, to calculate the odds ratio (OR) or standardized mean difference (SMD) and to draw a surface under the cumulative ranking curve of the neonatal and maternal outcomes of different treatments in GDM patients.Thirty-two randomized controlled trials (RCTs) were included in this NAM, including 6 kinds of treatments (metformin, metformin plus insulin, insulin, glyburide, acarbose, and placebo). The results of the NAM showed that regarding the incidence of macrosomia and LGA, metformin had lower incidence than glyburide (OR, 0.5411 and 0.4177). In terms of the incidence of admission to the NICU, insulin had higher incidence compared with glyburide (OR, 1.844). As for the incidence of neonatal hypoglycemia, metformin had lower incidence than insulin and glyburide (OR, 0.6331 and 0.3898), and insulin was lower than glyburide (OR, 0.6236). For mean birth weight, metformin plus insulin was lower than insulin (SMD, -0.5806), glyburide (SMD, -0.7388), and placebo (SMD, -0.6649). Besides, metformin was observed to have lower birth weight than glyburide (SMD, 0.2591). As for weight gain, metformin and metformin plus insulin were lower than insulin (SMD, -0.9166, -1.53). Ranking results showed that glyburide might be the optimum treatment regarding average glucose control, and metformin is the fastest in glucose control for GDM patients; glyburide have the highest incidence of macrosomia, preeclampsia, hyperbilirubinemia, neonatal hypoglycemia, shortest gestational age at delivery, and lowest mean birth weight; metformin (plus insulin when required) have the lowest incidence of macrosomia, PIH, LGA, RDS, low gestational age at delivery, and low birth weight. Besides, insulin had the highest incidence of NICU admission, acarbose had the lowest risk of neonatal hypoglycemia.Our study concluded that metformin is fastest in glucose control, with a more favorable pregnancy outcomes-would be a better option, but its rate of glucose control is the lowest.However, glyburide is the optimumtreatment regarding the rate of glucose control, but withmore adverse outcomes. This NAMbased on 32 RCTs will strongly help to guide further development of management for GDM patients, clinicians should carefully balance the risk-benefit profile of different treatments according to various situations.

Project description:BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce blood glucose, blood pressure, and body weight in patients with type 2 diabetes (T2D). However, the comparative long-term effectiveness and safety of SGLT2i among similar drugs, administered at different doses, have not been assessed. In this study, we compared the long-term effectiveness and safety of SGLT2i (dapagliflozin versus empagliflozin) as add-on therapy to hypoglycemic agents in T2D patients.MethodsThis study was a single-center, 3-year, retrospective, observational study. For all patients in the study, drugs were evaluated for safety by documenting adverse drug reactions. The primary effectiveness was evaluated as the difference between hemoglobin A1c (HbA1c) values obtained at baseline and those obtained after 36 months of treatment. The proportion of participants with HbA1c levels <7.0% and <6.5% was also analyzed.ResultsIn total, 680 patients were enrolled in this study. Using propensity score matching, 234 patients each from the dapagliflozin and empagliflozin groups were selected based on patient characteristics. After 36 months of treatment, clinical parameters (including HbA1c, fasting plasma glucose, alanine aminotransferase, triglyceride levels, body weight, and systolic blood pressure) decreased significantly in these groups. The changes from the baseline for the physiological values and clinical parameters did not vary among the different dose groups of SGLT2i. The incidence of adverse drug reactions was approximately 7-8%. All patients with observed serious adverse reactions were hospitalized for urinary tract infections.ConclusionOur study showed that the long-term continuous use of either dapagliflozin or empagliflozin as add-on therapy to hypoglycemic drugs for T2D patients is synergistically effective for lowering blood glucose, reducing body weight, and stabilizing blood pressure. Additionally, there was no significant difference in efficacy between dapagliflozin and empagliflozin, even with the administration of different doses of these agents.

Dataset Information

The efficacy of dapagliflozin combined with hypoglycemic drugs in treating type 2 diabetes: protocol for meta-analysis of randomized controlled trials.

Background

Methods/design

Discussion

Study registration

Publications

The efficacy of dapagliflozin combined with hypoglycemic drugs in treating type 2 diabetes: protocol for meta-analysis of randomized controlled trials.

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