scholarly journals Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Renal Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jae Hyun Bae ◽  
Eun-Gee Park ◽  
Sunhee Kim ◽  
Sin Gon Kim ◽  
Seokyung Hahn ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Meta Analysis ◽  
Sglt2 Inhibitors ◽  
Controlled Trials ◽  
Renal Outcomes ◽  
Randomized Controlled ◽  
Sodium Glucose Cotransporter ◽  
Stage Renal Disease ◽  
End Stage

Abstract 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.

scholarly journals Cardiovascular safety and efficacy of metformin-SGLT2i versus metformin-sulfonylureas in type 2 diabetes: systematic review and meta-analysis of randomized controlled trials

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Desye Gebrie ◽  
Desalegn Getnet ◽  
Tsegahun Manyazewal
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Adverse Events ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Safety And Efficacy ◽  
Randomized Controlled ◽  
Sodium Glucose Cotransporter

AbstractDiabetes is a serious threat to global health and among the top 10 causes of death, with nearly half a billion people living with it worldwide. Treating patients with diabetes tend to become more challenging due to the progressive nature of the disease. The role and benefits of combination therapies for the management of type 2 diabetes are well-documented, while the comparative safety and efficacy among the different combination options have not been elucidated. We aimed to systematically synthesize the evidence on the comparative cardiovascular safety and efficacy of combination therapy with metformin-sodium-glucose cotransporter-2 inhibitors versus metformin-sulfonylureas in patients with type 2 diabetes. We searched MEDLINE-PubMed, Embase, Cochrane Library, and ClinicalTrials.gov up to 15 August 2019 without restriction in the year of publication. We included randomized controlled trials of patients with type 2 diabetes who were on metformin-sodium-glucose cotransporter-2 inhibitors or metformin-sulphonylureas combination therapy at least for a year. The primary endpoints were all-cause mortality and serious adverse events, and the secondary endpoints were cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hypoglycemia, and changes in glycated hemoglobin A1c (HbA1c), body weight, fasting plasma glucose, blood pressure, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. We used a random-effects meta-analysis model to estimate mean differences for continuous outcomes and risk ratio for dichotomous outcomes. We followed PICOS description model for defining eligibility and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for reporting results. Of 3,190 citations, we included nine trials involving 10,974 participants. The pooled analysis showed no significant difference in all-cause mortality (risk ration [RR] = 0.93, 95% CI [0.52, 1.67]), serious adverse events (RR = 0.96, 95% CI [0.79, 1.17]) and adverse events (RR = 1.00, 95% CI [0.99, 1.02]) between the two, but in hypoglycemia (RR = 0.13, 95% CI [0.10, 0.17], P < 0.001). Participants taking metformin-sodium glucose cotransporter-2 inhibitors showed a significantly greater reduction in HbA1c (mean difference [MD] = − 0.10%, 95% CI [− 0.17, − 0.03], body weight (MD = − 4.57 kg, 95% CI [− 4.74, − 4.39], systolic blood pressure (MD = − 4.77 mmHg, 95% CI [− 5.39, − 4.16]), diastolic blood pressure (MD = − 2.07 mmHg, 95% CI [− 2.74, − 1.40], and fasting plasma glucose (MD = − 0.55 mmol/L, 95% CI [− 0.69, − 0.41]), p < 0.001. Combination therapy of metformin and sodium-glucose cotransporter-2 inhibitors is a safe and efficacious alternative to combination therapy of metformin and sulphonylureas for patients with type 2 diabetes who are at risk of cardiovascular comorbidity. However, there remains a need for additional long-term randomized controlled trials as available studies are very limited and heterogeneous.

scholarly journals Sodium-glucose co-transporter 2 inhibitors (SGLT2i); as a preventive factor of kidney failure in patients with type 2 diabetes; a meta-analysis of randomized controlled trials

2021 ◽  
Vol 10 (4) ◽  
pp. e35-e35
Author(s):  
Dorsa Jahangiri ◽  
Udit Narayan Padhi ◽  
Henu Kumar Verma ◽  
Bhaskar VKS Lakkakula ◽  
Rohollah Valizadeh ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Meta Analysis ◽  
Sglt2 Inhibitors ◽  
Renal Outcome ◽  
Diabetic Patients ◽  
Controlled Trials ◽  
Randomized Controlled

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new class of anti-diabetic drugs. SGLT2 inhibitors lower blood glucose levels by decreasing glucose reabsorption in the proximal renal tubule, resulting in increased urinary glucose and sodium excretion. Objective: This study was conducted to investigate the effects of SGLT2i on individual renal outcomes in diabetic patients. Methods: This study was a systematic review and meta-analysis of clinical trials. A comprehensive search of Cochrane Central Register of Controlled Trials was conducted in the Cochrane Library and PubMed, to identify relevant articles focusing on SGLT2i and chronic kidney disease (CKD) in diabetic patients. The most recent article search was conducted on July 12, 2021. Results: Seven randomized controlled trials (RCTs) were included in the meta-analysis. Two trials were comparing dapagliflozin, two comparing empagliflozin, one comparing ertugliflozin, one comparing canagliflozin, and one comparing sotagliflozin. Composite renal outcome and acute kidney injury (AKI) was found in seven and four studies, respectively. Data on end-stage kidney disease (ESKD) and albuminuria or initiation of renal replacement therapy were reported in the two studies. The pooled risk ratio (RR) 95% confidence interval (CI) for the composite renal outcome was 0.54 (0.50–0.59), with 92 % heterogeneity. The pooled RR for AKI was 0.77 (0.66–0.89), with no heterogeneity. A significant lower incidence of albuminuria (RR: 0.69; 95% CI: 0.59–0.81), initiation of renal replacement therapy (RR: 0.71; 95% CI: 0.58–0.87), was observed following the use of SGLT2 inhibitors. Conclusion: Our findings confirm that the SGLT2 inhibitors can reduce the risk of albuminuria, AKI and renal replacement therapy in ESKD patients with T2D (type 2 diabetes). These meta-analyses provide substantial evidence supporting the beneficial effect of SGLT2 inhibitors on reducing CKD events in individuals with T2D.

Risk of volume reduction associated with sodium-glucose cotransporter-2 inhibitors treatment: a meta-analysis of randomized controlled trials

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
X.I Rong ◽  
X Li ◽  
Q Gou ◽  
X.P Chen
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Meta Analysis ◽  
Sglt2 Inhibitors ◽  
Volume Reduction ◽  
Controlled Trials ◽  
Older Individuals ◽  
Osmotic Diuresis ◽  
Sodium Glucose Cotransporter

Abstract Introduction Sodium-glucose cotransporter-2 (SGLT2) inhibitors is a newly class of drug which improving glycemia by enhancing glycosuria, subsequently reducing blood pressure by osmotic diuresis and natriuresis. There are multiple large-scale randomized control trials demonstrating that SGLT2 inhibitors had salutary effect on cardiovascular-renal outcome, especially on heart failure. Although SGLT2 inhibitors exhibited promising potential value on treatment for type 2 diabetes mellitus (T2DM) with cardiovascular-renal comorbidities, the potential adverse events (AEs) related to osmotic diuresis such as volume reduction should not be neglected. Moreover, older individuals, those with moderate renal impairment, and those receiving antihypertensive therapies are susceptible to adverse events related to volume reduction. Purpose To assess the association between sodium-glucose cotransporter-2 inhibitors and risk of volume reduction in patients with type 2 diabetes mellitus. Methods A systematic literature retrieval was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception up to 10 December 2019, Data for study characteristics and outcomes of interest were extracted from each eligible study. Pooled risk ratios (RRs) with 95% confidence interval (CI) for volume reduction was calculated using random-effects model. Result A total of 51 studies (n=56,866) were included in our meta-analysis, with a result of 1,337 incident volume reduction cases (814 in the SGLT2 inhibitors group, 523 in the control group). The pooled RR was 1.15 (95% CI: 1.03–1.28). It is evident that receiving SGLT2 inhibitors had increased the risk of volume reduction, when stratified by placebo-control or active-control the result was consistent. Conclusion Our meta-analysis has demonstrated that SGLT2 inhibitors increase the risk of volume reduction in patients with T2DM. It is necessary to attention for the risk of volume reduction associated with SGLT2 inhibitors, especially in older individuals, those with moderate renal impairment, and those receiving antihypertensive therapies. SGLT2 inhibitors vs control Funding Acknowledgement Type of funding source: None

scholarly journals Renal outcomes in Asian patients with type 2 diabetes mellitus treated with SGLT2 inhibitors: a systematic review and meta-analysis of randomized controlled trials

2021 ◽  
Author(s):  
Shi-di Zhao ◽  
Ling Zhou ◽  
Yi-ying Tao ◽  
Yue Yue ◽  
Jia-xin Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Controlled Trials ◽  
Control Groups ◽  
Renal Outcomes ◽  
Randomized Controlled ◽  
Asian Patients

Abstract Aim This study investigated the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on renal outcomes in Asian patients with type 2 diabetes mellitus (T2DM). Materials and methods We searched Medline, EMBASE, and the Cochrane Library to identify randomized controlled trials published up to April 2020 that compared SGLT2 inhibitors with placebo or active comparator and reported any renal outcomes in Asian patients with T2DM. Random effects models and inverse variance weighting were used to calculate relative risks with 95% confidence intervals (CIs). Results We included 14 studies, totaling 3792 patients, in the analysis. In the short term, SGLT2 inhibitors significantly slowed estimated glomerular filtration rate (eGFR) decline (MD: 0.80; 95% CI: 0.66 to 0.94; p < 0.00001) and reduced Scr levels (SMD: − 0.17; 95% CI: − 0.23 to − 0.10; p < 0.00001) as compared with the control groups. The SGLT2 inhibitor group also had an advantage over the control group in lowering uric acid (UA) (SMD: − 1.2; 95% CI: − 1.30 to − 1.11; p < 0.00001). There was no significant difference in urinary albumin creatinine ratio (UACR) reduction between the SGLT2 inhibitor and control groups (MD: − 8.87; 95% CI: − 19.80 to 2.06; p = 0.11). However, dapagliflozin does appear to reduce albuminuria (p = 0.005). Lastly, SGLT2 inhibitors increased the incidence of adverse events (AEs) related to renal function (OR: 1.90; 95% CI: 1.24 to 2.91; p = 0.003), but did not increase the incidence of renal impairment (OR: 0.85; 95% CI: 0.40 to 1.81; p = 0.68). Conclusion The use of SGLT2 inhibitors in Asian patients with T2DM can help delay the decline of eGFR and reduce Scr and UA. Although SGLT2 inhibitors have no overall advantage in reducing albuminuria, dapagliflozin does appear to reduce albuminuria, and while they may increase the occurrence of AEs related to renal function, they do not increase the incidence of renal impairment.

scholarly journals Systematic Review and Meta-Analysis of Randomized Controlled Trials on the Effect of SGLT2 Inhibitor on Blood Leptin and Adiponectin Level in Patients with Type 2 Diabetes

2019 ◽  
Vol 51 (08) ◽  
pp. 487-494 ◽  
Author(s):  
Peili Wu ◽  
Weiheng Wen ◽  
Jitong Li ◽  
Jie Xu ◽  
Min Zhao ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Sglt2 Inhibitor ◽  
Placebo Treatment ◽  
Sglt2 Inhibitors ◽  
Controlled Trials ◽  
Beneficial Effects ◽  
Randomized Controlled

AbstractSodium glucose cotransporter 2 (SGLT2) inhibitors are a new kind of hypoglycemic drugs that improve glucose homeostasis by inhibiting renal glucose reabsorption. Recent studies have shown that SGLT2 inhibitors can also mediate body metabolism through regulation of adipokines level, but the effects of SGLT2 inhibitors on the concentration of adipokines (leptin and adiponectin) remains controversial. This meta-analysis was set out to evaluate the changes in circulating leptin and adiponectin levels in patients with type 2 diabetes mellitus (T2DM) receiving SGLT2 inhibitors therapy. Ten randomized controlled trials (RCTs), that evaluated the effects of SGLT2 inhibitors on blood leptin and adiponectin levels in patients with type 2 diabetes, were identified by performing a systematic search of Pubmed, Embase, Cochrane, and Web of science databases through July 2018. Data were calculated using a random-effects model and presented as standardized mean difference (SMD) and 95% confidence interval (CI). Compared with placebo, treatment with SGLT2 inhibitors contributed to a decreased circulating leptin levels (SMD −0.29, 95% CI −0.56, −0.03) and an increased circulating adiponectin levels (SMD 0.30, 95% CI 0.22, 0.38). SGLT2 inhibitor treatment was associated with decreased circulating leptin levels and increased circulating adiponectin levels, which might contribute to the beneficial effects of SGLT2 inhibitors on metabolic homeostasis.

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