SGLT2 inhibitors and atrial fibrillation in type 2 diabetes: a systematic review with meta-analysis of 16 randomized controlled trials.
ABSTRACT: BACKGROUND:Type 2 diabetes is closely related to an increased risk of atrial fibrillation (AF) and atrial flutter (AFL). Whether sodium-glucose cotransporter 2 (SGLT2) inhibitors can attenuate AF/AFL progression remains unclear. METHODS:We searched electronic databases (PubMed, Embase and ClinicalTrials.gov) from their inception to January 2020 for trials evaluating the AF outcomes of SGLT2 inhibitors in patients with type 2 diabetes. The data search and extraction were conducted with a standardized data form and any conflicts were resolved by consensus. Relative risks (RRs) with 95% confidence intervals (CIs) were used for binary variables, and the weighed mean differences (WMDs) with the standard deviation (SDs) were applied for continuous variables. RESULTS:We included data from 16 identified trials consisting of 38,335 patients with type 2 diabetes. Incorporated data demonstrated that compared to placebo, SGLT2 inhibitors significantly reduced AF/AFL (RR: 0.76; 95% CI 0.65-0.90; p?=?0.001) and all-cause mortality (RR: 0.91; 95% CI 0.83-0.99; p?=?0.03). AF/AFL reductions were not modified by age, body weight, glycated haemoglobin (HbA1c), or systolic blood pressure (SBP) at baseline (all p-interactions?>?0.3). SGLT2 inhibitors also significantly reduced heart failure events (RR: 0.73; 95% CI 0.64-0.84; p?
Project description:INTRODUCTION:The aim of this study was to assess the efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors in East Asians with type 2 diabetes mellitus (T2DM). METHODS:A literature search that focused primarily on the PubMed, Embase, and Cochrane library databases was performed. All randomized controlled trials (RCTs) which satisfied the inclusion and exculsion criteria were eligible to be included in the meta-analysis. Risk ratios (RRs) and weighted mean differences (WMDs) were used as statistical indicators for the analysis of dichotomous data and continuous outcomes, respectively. Pooled estimates were obtained using random-effects models in RevMan version 5.3.5. RESULTS:Thirty-three RCTs (8496 randomized patients) fulfilled the eligibility criteria for inclusion in the meta-analysis. The meta-analysis showed that, compared with the control group, the use of SGLT2 inhibitors improved both glycated hemoglobin (HbA1c) in patients (WMD - 0.73%; 95% confidence interval [CI] - 0.84, - 0.61) and the percentage of patients with HbA1c < 7% (RR 2.33; 95% CI 1.74, 3.12); lowered both fasting plasma glucose (WMD - 28.47 mg/dl; 95% CI - 32.86, - 24.08) and postprandial glucose (WMD - 52.32 mg/dl; 95% CI - 67.67, - 39.96); reduced body weight (WMD - 1.73 kg; 95% CI - 2.28, - 1.17); and did not increase the risk of hypoglycemia (RR 1.27; 95% CI 0.89, 1.82) and urinary tract infections (RR 0.93; 95% CI 0.68, 1.27). However, SGLT2 inhibitors did increase the risk of genital tract infections (GTIs) (RR 1.73; 95% CI 1.02, 2.96). The stratified analysis showed that patients with higher HbA1c levels at baseline may achieve a greater improvement in HbA1c after taking SGLT2 inhibitors, while those with higher body weight or a longer history of diabetes may have an increased risk of developing GTIs. CONCLUSION:Current research suggests that SGLT2 inhibitors have favorable efficacy and safety in East Asian patients with T2DM.
Project description:AIMS/INTRODUCTION:Non-alcoholic fatty liver disease (NAFLD) is increasingly common in patients with type 2 diabetes mellitus. Currently, some studies have found that sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new hypoglycemic drug, can improve non-alcoholic fatty liver in addition to its hypoglycemic effect. Thus, we undertook a meta-analysis of randomized controlled trials to evaluate the efficacy of SGLT2 inhibitors on the treatment of NAFLD. MATERIALS AND METHODS:PubMed, Embase and the Cochrane Library were searched for randomized controlled trials of SGLT2 inhibitors in patients with NAFLD and type 2 diabetes mellitus up to 1 October 2019. Differences were expressed as weight mean difference (WMD) with 95% confidence interval (CI) for continuous outcomes. The I2 statistic was applied to evaluate the heterogeneity of studies. RESULTS:A total of six trials including 309 patients were selected into our meta-analysis. SGLT2 inhibitors could reduce alanine aminotransferase (WMD -11.05 IU/L, 95% CI -19.85, -2.25, P = 0.01) and magnetic resonance imaging proton density fat fraction (WMD -2.07%, 95% CI -3.86, -0.28, P = 0.02). However, SGLT2 inhibitors did not reduce aspartate aminotransferase (WMD -1.11 IU/L, 95% CI -2.39, 0.17, P = 0.09). In addition, secondary outcomes, such as bodyweight and visceral fat area, were also reduced (WMD -1.62 kg, 95% CI -2.02, -1.23, P < 0.00001; WMD -19.98 cm2 , 95% CI -27.18, -12.79, P < 0.00001, respectively). CONCLUSIONS:SGLT2 inhibitors can significantly decrease alanine aminotransferase and liver fat, accompanied with weight loss, which might have a positive effect on fatty liver in patients with type 2 diabetes mellitus. The limitation is that the sample size of the studies was small. Therefore, more large randomized controlled trials specified on NAFLD are required to evaluate these results.
Project description:This study was conducted to investigate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on individual renal outcomes in patients with type 2 diabetes. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to September 2017 to identify randomized controlled trials comparing SGLT2 inhibitors with placebo or antidiabetic drugs and reporting any renal outcomes in patients with type 2 diabetes. Additionally, we identified 4 articles which were published after the predefined period to include relevant data. A meta-analysis was performed to calculate weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs) for each renal outcome. We included 48 studies involving 58,165 patients in the analysis. SGLT2 inhibitors significantly lowered urine albumin-to-creatinine ratio (UACR) (WMD, -14.64 mg/g; 95% CI, -25.15 to -4.12; P = 0.006) compared with controls. The UACR-lowering effects of SGLT2 inhibitors were greater with a higher baseline UACR. Overall changes in estimated glomerular filtration rate (eGFR) were comparable between two groups (WMD, 0.19 mL/min/1.73 m2; 95% CI, -0.44 to 0.82; P = 0.552). However, SGLT2 inhibitors significantly slowed eGFR decline in patients with a higher baseline eGFR and a longer duration of treatment. Compared with controls, SGLT2 inhibitors significantly reduced the risk of microalbuminuria (RR, 0.69; 95% CI, 0.49 to 0.97; P = 0.032), macroalbuminuria (RR, 0.49; 95% CI, 0.33 to 0.73; P < 0.001), and worsening nephropathy (RR, 0.73; 95% CI, 0.58 to 0.93; P = 0.012). In addition, the risk of end-stage renal disease was significantly lower in SGLT2 inhibitors than in controls (RR, 0.70; 95% CI, 0.57 to 0.87; P = 0.001). In conclusion, SGLT2 inhibitors had beneficial renal effects by lowering the risk of albuminuria development or progression and reducing the risk of end-stage renal disease compared with placebo or other antidiabetic drugs.
Project description:To evaluate the relative efficacy of ranibizumab (RBZ) monotherapy or combined with laser (RBZ + Laser) versus laser monotherapy for the treatment of diabetic macular edema (DME).A comprehensive literature search using PUBMED, ClinicalTrials.gov, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing RBZ or RBZ + Laser to laser monotherapy in patients with DME. Efficacy estimates were determined by comparing weighted mean differences (WMD) in the change of best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline, and the risk ratios (RR) for the proportions of patients with at least 15 letters change from baseline. Safety analysis estimated the RR of cardiac disorders at 6 to 12 months in RBZ therapy vs. laser monotherapy. Statistical analysis was performed using the RevMan 5.1 software.Seven RCTs were selected for this meta-analysis, including 1749 patients (394 patients in the RBZ group, 642 patients in the RBZ + Laser group, and 713 patients in the laser group). RBZ and RBZ + Laser were superior to laser monotherapy in the mean change of BCVA and CMT from baseline (WMD?=?5.65, 95% confidence interval (CI), 4.44-6.87, P<0.00001; WMD ?=?5.02, 95% CI, 3.83-6.20, P<0.00001, and WMD ?=?-57.91, 95% CI, -77.62 to -38.20, P<0.00001; WMD ?=?-56.63, 95% CI, -104.81 to -8.44, P?=?0.02, respectively). The pooled RR comparing the proportions of patients with at least 15 letters improvement or deterioration were also in favor of RBZ and RBZ + Laser (RR?=?2.94, 95% CI, 1.82-4.77, P<0.00001; RR?=?2.04, 95% CI, 1.50-2.78, P<0.00001, and RR?=?0.21, 95% CI, 0.06-0.71, P?=?0.01; RR?=?0.52, 95% CI, 0.29-0.95, P?=?0.03, respectively). There were no significant differences between RBZ and RBZ + Laser for any of the parameters. There were no difference in the safety profile between RBZ and laser.RBZ and RBZ + Laser had better visual and anatomic outcomes than laser monotherapy in the treatment of DME. RBZ + Laser seemed to be equivalent to RBZ.
Project description:INTRODUCTION:The purpose of this study was to compare insulin degludec with insulin glargine in terms of efficacy and safety in patients with type 2 diabetes. METHODS:We systematically searched PubMed, Embase, Web of Science, and Cochrane Library databases for randomized controlled trials published prior to 13 August 2018 (no language restrictions) which compared insulin degludec with insulin glargine. Our main endpoints were glycemic control, hypoglycemic event, weight gain, and serious adverse events (SAEs). We assessed pooled data using random-effects models. RESULTS:A total of 15 studies that included 9619 patients in the insulin degludec arm of the studies and 7075 patients in the insulin glargine arm were identified and subsequently assessed. Our analysis showed that compared with insulin glargine, insulin degludec yielded an improved mean reduction in fasting plasma glucose (FPG) (weighted mean difference [WMD] - 5.20 mg/dL, 95% confidence interval [CI] - 7.34, - 3.07, P < 0.00001) and a lower ratio of participants experiencing ≥ 1 severe hypoglycemic event (relative risk [RR] 0.68, 95% CI 0.50, 0.93, P = 0.01) and nocturnal hypoglycemia (RR 0.81, 95% CI 0.75, 0.88, P < 0.0001); however, in the insulin degludec group there was a lower ratio of participants with glycated hemoglobin (HbA1c) of ≤ 7.0% (RR 0.92, 95% CI 0.86, 0.98, P = 0.01). There was no statistically significant difference between the two treatment groups for HbA1c reduction (WMD 0.03, 95% CI - 0.00, 0.07, P = 0.08), body weight gain (WMD 0.12, 95% CI - 0.19, 0.43, P = 0.46), and proportion of participants with SAEs (RR 0.97, 95% CI 0.92, 1.02, P = 0.20). CONCLUSIONS:Insulin degludec and insulin glargine provide similar glycemic control, but insulin degludec also lowers the risk of hypoglycemia. Consequently, insulin degludec may be an alternative treatment for the management of patients with type 2 diabetes who are prone to hypoglycemia with insulin glargine.
Project description:Objectives:To evaluate the efficacy of Traditional Chinese Medicine, specifically Jianpi Bushen (JPBS) therapy, for treatment of patients with chronic kidney disease (CKD) anemia. Methods:Randomized controlled trials of JPBS therapy for CKD anemia were searched and selected from seven electronic databases. The Cochrane collaboration tool was used to conduct methodological quality assessment. RevMan v5.3 software was utilized to perform data analysis. Results:In total, 12 randomized controlled trials with 799 patients met the meta-analysis criteria. The aggregated results indicated that JPBS therapy is beneficial for CKD anemia by improving the clinical efficacy rate [risk ratio (RR) = 1.23, 95% confidence interval (CI): (1.14, 1.33), P < 0.00001] and hemoglobin (Hb) [weighted mean difference (WMD) = 9.55, 95% CI: (7.97, 11.14), P < 0.00001], serum ferritin (SF) [WMD = 6.22, 95% CI: (2.65, 9.79), P = 0.0006], red blood cell (RBC) [WMD = 0.31, 95% CI: (0.24, 0.38), P < 0.00001], hematocrit (HCT) [WMD = 2.95, 95% CI: (2.36, 3.54), P < 0.00001], serum creatinine (SCr) [WMD = 64.57, 95% CI: (33.51, 95.64), P < 0.0001], and blood urea nitrogen (BUN) levels [WMD = 3.76, 95% CI: (2.21, 5.31), P <0.00001]. Furthermore, evidence suggests that JPBS therapy is safe and does not increase adverse reactions compared with western medicine (WM) alone. Conclusion:This study found that JPBS therapy has a positive effect on the treatment of CKD anemia. However, more well-designed, double-blind, large-scale randomized controlled trials are needed to assess the efficacy of JPBS therapy in the treatment of CKD anemic patients.
Project description:AIM:To evaluate the effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes. METHODS:We conducted systematic searches of PubMed, Embase and Cochrane Central Register of Controlled Trials up to June 2016 and included randomized controlled trials of SGLT2 inhibitors in adult type 2 diabetic patients reporting estimated glomerular filtration rate (eGFR) and/or urine albumin/creatinine ratio (ACR) changes. Data were synthesized using the random-effects model. RESULTS:Forty-seven studies with 22,843 participants were included. SGLT2 inhibition was not associated with a significant change in eGFR in general (weighted mean difference (WMD), -0.33 ml/min per 1.73 m2, 95% CI [-0.90 to 0.23]) or in patients with chronic kidney disease (CKD) (WMD -0.78 ml/min per 1.73 m2, 95% CI [-2.52 to 0.97]). SGLT2 inhibition was associated with eGFR reduction in short-term trials (WMD -0.98 ml/min per 1.73 m2, 95% CI [-1.42 to -0.54]), and with eGFR preservation in long-term trials (WMD 2.01 ml/min per 1.73 m2, 95% CI [0.86 to 3.16]). Urine ACR reduction after SGLT2 inhibition was not statistically significant in type 2 diabetic patients in general (WMD -7.24 mg/g, 95% CI [-15.54 to 1.06]), but was significant in patients with CKD (WMD -107.35 mg/g, 95% CI [-192.53 to -22.18]). CONCLUSIONS:SGLT2 inhibition was not associated with significant changes in eGFR in patients with type 2 diabetes, likely resulting from a mixture of an initial reduction of eGFR and long-term renal function preservation. SGLT2 inhibition was associated with statistically significant albuminuria reduction in type 2 diabetic patients with CKD.
Project description:BACKGROUND:Guidelines differ with regard to indications for initial combination pharmacotherapy for type 2 diabetes. AIMS:To compare the efficacy and safety of (i) sodium-glucose cotransporter 2 (SGLT2) inhibitor combination therapy in treatment-naïve type 2 diabetes adults; (ii) initial high and low dose SGLT2 inhibitor combination therapy. METHODS:PubMed, Embase and Cochrane Library were searched for randomised controlled trials (RCTs) of initial SGLT2 combination therapy. Mean difference (MD) for changes from baseline (HbA1c, weight, blood pressure) after 24?26 weeks of treatment and relative risks (RR, safety) were calculated using a random-effects model. Risk of bias and quality of evidence was assessed. RESULTS:In 4 RCTs (n = 3749) there was moderate quality evidence that SGLT2 inhibitor/metformin combination therapy resulted in a greater reduction in HbA1c (MD (95% CI); -0.55% (-0.67, -0.43)) and weight (-2.00 kg (-2.34, -1.66)) compared with metformin monotherapy, and a greater reduction in HbA1c (-0.59% (-0.72, -0.46)) and weight (-0.57 kg (-0.89, -0.25)) compared with SGLT2 inhibitor monotherapy. The high dose SGLT2 inhibitor/metformin combination resulted in a similar HbA1c but greater weight reduction; -0.47 kg (-0.88, -0.06) than the low dose combination therapy. The RR of genital infection with combination therapy was 2.22 (95% CI 1.33, 3.72) and 0.69 (95% CI 0.50, 0.96) compared with metformin and SGLT2 inhibitor monotherapy, respectively. The RR of diarrhoea was 2.23 (95% CI 1.46, 3.40) with combination therapy compared with SGLT2 inhibitor monotherapy. CONCLUSIONS:Initial SGLT2 inhibitor/metformin combination therapy has glycaemic and weight benefits compared with either agent alone and appears relatively safe. High dose SGLT2 inhibitor/metformin combination therapy appears to have modest weight, but no glycaemic benefits compared with the low dose combination therapy.
Project description:OBJECT:To compare the safety and efficacy of rigid ureteroscopic lithotripsy (rigid URSL) and percutaneous nephrolithotomy (PCNL) in treating large proximal ureteral stones. METHODS:A systematic search of PubMed, EMBASE, Cochrane Library, and Web of Science databases was performed to find out relevant studies. After literature screening according to the predetermined inclusion and exclusion criteria, data of eligible studies was extracted and then a meta-analysis was conducted via RevMan 5.3 software. RESULTS:Five randomized controlled trials (RCTs), one prospective and four retrospective cohort studies involving 837 patients were included. Patients underwent rigid URSL were associated with shorter operation time (WMD, -23.66min; 95%CI, -45.00 to -2.32; p = 0.03), shorter hospital stay (WMD, -2.76d; 95%CI, -3.51 to -2.02; p< 0.00001), lower 3rd-day (RR, 0.73; 95%CI, 0.66 to 0.82; p < 0.00001) and 1st-month (RR, 0.82; 95%CI, 0.77 to 0.87; p < 0.00001) stone-free rate, higher risk of conversion to other surgical procedures (RR, 4.28; 95%CI, 1.93 to 9.46; p = 0.0003), higher incidence of migration (RR, 28.49; 95%CI, 9.12 to 89.00; p < 0.00001) and ureteral perforation (RR, 6.06; 95%CI, 1.80 to 20.44; p = 0.004), lower risk of fever (RR, 0.64; 95%CI, 0.42 to 0.97; p = 0.04), transfusion (RR, 0.19; 95%CI, 0.04 to 0.85; p = 0.03) and hematuria (RR, 0.38; 95%CI, 0.25 to 0.57; p < 0.0001). No significant difference was observed in terms of incidence of embolization, pain and ureterostenosis. When cohort studies or studies in which flexible ureteroscopy was used as an intraoperative auxiliary procedure were excluded, we both found that most of the results kept stable. CONCLUSIONS:Both PCNL and rigid URSL are safe for patients with large proximal ureteral stones while PCNL is more effective in stone clearance.
Project description:<h4>Background</h4>Despite the number of medications for type 2 diabetes, many people with the condition do not achieve good glycaemic control. Some existing glucose-lowering agents have adverse effects such as weight gain or hypoglycaemia. Type 2 diabetes tends to be a progressive disease, and most patients require treatment with combinations of glucose-lowering agents. The sodium glucose co-transporter 2 (SGLT2) receptor inhibitors are a new class of glucose-lowering agents.<h4>Objective</h4>To assess the clinical effectiveness and safety of the SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes.<h4>Data sources</h4>MEDLINE, Embase, Cochrane Library (all sections); Science Citation Index; trial registries; conference abstracts; drug regulatory authorities; bibliographies of retrieved papers.<h4>Inclusion criteria</h4>Randomised controlled trials of SGLT2 receptor inhibitors compared with placebo or active comparator in type 2 diabetes in dual or combination therapy.<h4>Methods</h4>Systematic review. Quality assessment used the Cochrane risk of bias score.<h4>Results</h4>Seven trials, published in full, assessed dapagliflozin and one assessed canagliflozin. Trial quality appeared good. Dapagliflozin 10 mg reduced HbA1c by -0.54% (weighted mean differences (WMD), 95% CI -0.67 to -0.40) compared to placebo, but there was no difference compared to glipizide. Canagliflozin reduced HbA1c slightly more than sitagliptin (up to -0.21% vs sitagliptin). Both dapagliflozin and canagliflozin led to weight loss (dapagliflozin WMD -1.81 kg (95% CI -2.04 to -1.57), canagliflozin up to -2.3 kg compared to placebo).<h4>Limitations</h4>Long-term trial extensions suggested that effects were maintained over time. Data on canagliflozin are currently available from only one paper. Costs of the drugs are not known so cost-effectiveness cannot be assessed. More data on safety are needed, with the Food and Drug Administration having concerns about breast and bladder cancers.<h4>Conclusions</h4>Dapagliflozin appears effective in reducing HbA1c and weight in type 2 diabetes, although more safety data are needed.