Association Between SGLT2is and Cardiovascular and Respiratory Diseases: A Meta-Analysis of Large Trials.

The association between sodium-glucose cotransporter 2 inhibitors (SGLT2is) and various cardiovascular and respiratory diseases is unestablished. This meta-analysis aimed to explore whether use of SGLT2is is significantly associated with the occurrences of 80 types of cardiovascular diseases and 55 types of respiratory diseases. Large randomized trials of SGLT2is were included in analysis. Meta-analysis was conducted to synthesize risk ratio (RR) and 95% confidence interval (CI). Nine large trials were included in analysis. Compared to placebo, SGLT2is were associated with the reduced risks of 9 types of cardiovascular diseases (e.g., atrial fibrillation [RR 0.78, 95% CI 0.67-0.91], bradycardia [RR 0.60, 95% CI 0.40-0.89], and hypertensive emergency [RR 0.29, 95% CI 0.12-0.72]) and 11 types of respiratory diseases (e.g., chronic obstructive pulmonary disease [RR 0.77, 95% CI 0.61-0.97], asthma [RR 0.57, 95% CI 0.35-0.95], and sleep apnoea syndrome [RR 0.36, 95% CI 0.15-0.87]). The results of random-effects meta-analysis were similar with those of fixed-effects meta-analysis. No heterogeneity or only little heterogeneity was found in most meta-analyses. No publication bias was observed in most of the meta-analyses conducted in this study. SGLT2is were not significantly associated with the other 115 cardiovascular and respiratory diseases. SGLT2is are associated with the reduced risks of 9 types of cardiovascular diseases (e.g., atrial fibrillation, bradycardia, and hypertensive emergency) and 11 types of respiratory diseases (e.g., chronic obstructive pulmonary disease, asthma, and sleep apnoea syndrome). This proposes the potential of SGLT2is to be used for prevention of these cardiovascular and respiratory diseases.

Comparative efficacy of 5 sodium glucose cotransporter 2 inhibitor and 7 glucagon-like peptide 1 receptor agonists interventions on cardiorenal outcomes in type 2 diabetes patients: A network meta-analysis based on cardiovascular or renal outcome trials.

BACKGROUND: Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been demonstrated to be able to improve the cardiovascular and renal prognosis in patients with type 2 diabetes (T2D). However, the relative efficacy of various SGLT2 inhibitors and GLP-1 RAs on cardiorenal outcomes is unestablished. METHODS: We searched PubMed and Embase for relevant cardiovascular or renal outcome trials (CVOTs). Endpoints of interest were major adverse cardiovascular events (MACE), stroke, myocardial infarction (MI), cardiovascular death (CVD), all-cause death (ACD), kidney function progression (KFP), and hospitalization for heart failure (HHF). Bayesian network meta-analysis was conducted to produce pooled hazard ratio (HR) and 95% confidence interval (CI). We calculated the probability values of surface under the cumulative ranking curve to rank active and placebo interventions. RESULTS: Fourteen COVTs were included in analysis. Sotagliflozin (HR 0.76, 95% CI 0.61-0.94), subcutaneous semaglutide, and albiglutide lowered MACE versus lixisenatide among others. Sotagliflozin (HR 0.59, 95% CI 0.40-0.89), canagliflozin, and empagliflozin lowered HHF versus subcutaneous semaglutide among others. Dapagliflozin and empagliflozin lowered KFP versus exenatide among others. Empagliflozin and oral semaglutide lowered CVD versus dapagliflozin among others. Sotagliflozin (HR 0.65, 95% CI 0.47-0.91) and albiglutide lowered MI versus ertugliflozin among others. Sotagliflozin (HR 0.56, 95% CI 0.37-0.85) and subcutaneous semaglutide lowered stroke versus empagliflozin among others. Oral semaglutide and empagliflozin lowered ACD versus subcutaneous semaglutide among others. The maximum surface under the cumulative ranking curve values followed sotagliflozin, subcutaneous semaglutide, and albiglutide in lowering MACE; sotagliflozin, canagliflozin, and empagliflozin in lowering HHF; dapagliflozin and empagliflozin in lowering KFP; empagliflozin and oral semaglutide in lowering CVD; sotagliflozin and albiglutide in lowering MI; sotagliflozin and subcutaneous semaglutide in lowering stroke; and oral semaglutide and empagliflozin in lowering ACD. CONCLUSIONS: This updated network meta-analysis reproduced the findings in the first network meta-analysis, and moreover revealed that sotagliflozin was one of the most effective drugs as for lowering MI, stroke, MACE, and HHF, whereas ertugliflozin was not. These findings will provide the according evidence regarding the usage of specific SGLT2 inhibitors and GLP-1 RAs in T2D patients for prevention of specific cardiorenal endpoints.

Comprehensive analysis of the safety of semaglutide in type 2 diabetes: a meta-analysis of the SUSTAIN and PIONEER trials.

The PIONEER and SUSTAIN serial trials are designed to assess the efficacy outcomes with semaglutide in patients with type 2 diabetes, but are not powered to assess various safety outcomes. We sought to assess the risk of semaglutide in leading to various serious adverse events (SAEs) in patients with type 2 diabetes. Studies eligible for inclusion were the PIONEER and SUSTAIN trials of semaglutide. We conducted meta-analysis to generate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Meta-analysis was performed using both random-effects and fixed-effects model to evaluate the robustness of pooled results. We implemented subgroup analysis according to drug dosages and routes of administration and type of comparators. Twenty-one trials were included. Semaglutide versus control significantly reduced total SAEs (RR 0.92, 95% CI 0.87-0.97; I2 = 0) and atrial fibrillation (RR 0.69, 95% CI 0.50-0.95; I2 = 0), but significantly increased deep vein thrombosis (RR 3.66, 95% CI 1.09-12.25; I2 = 0) and diarrhoea (RR 2.66, 95% CI 1.19-5.95; I2 = 0). Semaglutide had no significant effects on 248 other kinds of SAEs. No statistically significant subgroup effects were observed. Semaglutide has a good safety profile in general and reduces atrial fibrillation by 31%, but increases diarrhoea by 166% and deep vein thrombosis by 266%. These findings may guide that semaglutide should be preferred or avoided in T2D patients with specific susceptibility factors.

[Effect of probiotic supplementation during pregnancy and infancy in preventing atopic dermatitis in children: a Meta analysis].

OBJECTIVE: To systematically review the effect of probiotic supplementation during pregnancy and infancy in preventing atopic dermatitis in children. METHODS: RevMan5.3 was used to perform a Meta analysis of randomized controlled trials on the effect of probiotic supplementation during pregnancy and infancy in preventing atopic dermatitis in children published between January 2008 and May 2018 across the world. A subgroup analysis was conducted according to the type of probiotics for intervention, follow-up time, time of probiotic supplementation, and study areas. RESULTS: A total of 22 articles were selected, with 3 280 cases in the intervention group and 3 281 cases in the control group. The results of pooled effect size showed that probiotic supplementation during pregnancy and/or infancy significantly reduced the incidence rate of atopic dermatitis (RR=0.81, 95%CI: 0.70-0.93, P<0.05). According to the subgroup analysis, the intervention with Lactobacillus and Bifidobacterium had a significant effect (RR=0.68, 95%CI: 0.52-0.90, P<0.05); probiotic supplementation during both pregnancy and infancy also had a significant effect (RR=0.77, 95%CI: 0.66-0.90, P<0.05); probiotic supplementation during pregnancy and/or infancy had a better effect in preventing atopic dermatitis in children aged ≤2 years than in those aged >2 years (RR=0.74, 95%CI: 0.61-0.90, P<0.05); probiotic supplementation had a significant effect in Australia (RR=0.83, 95%CI: 0.73-0.96, P<0.05) and Europe/the United States (RR=0.74, 95%CI: 0.61-0.91, P<0.05). Heterogeneity was mainly due to follow-up time (I2=62.7%) and time of probiotic supplementation (I2=53.5%). CONCLUSIONS: Probiotic supplementation during pregnancy and infancy helps to prevent atopic dermatitis in children, and mixed Lactobacillus-Bifidobacterium intervention has a better effect.