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Summary: In this meta‐analysis, we aim to evaluate the risk of gallbladder and biliary disease of weight management strategies and investigate the association between weight reduction and risk of gallbladder or biliary disease. Randomized controlled trials (RCTs) with a duration of at least 12 weeks that compare antiobesity medications (AOMs) with placebo or bariatric surgery with less intensive weight management strategy were concluded. Weight management strategy was associated with a significant increased risk of gallbladder or biliary disease (OR 1.361, 95% CI 1.147 to 1.614, P < 0.001, I2 = 3.5%), cholelithiasis, cholecystitis, and cholecystectomy compared with placebo or controls. The increased risk of gallbladder or biliary disease was observed both in pharmacotherapies subgroup and bariatric surgery subgroup. With regards of specific pharmacotherapies, an increased risk of gallbladder or biliary disease was observed in trials with glucagon‐like peptide 1 receptor agonist (GLP‐1 RA) treatments. In addition, trials with indication of obesity and overweight treatment and trials with higher doses showed significant higher risk of gallbladder or biliary disease compared with placebo or controls. In conclusion, weight management strategy was associated with an increased risk of gallbladder or biliary disease when compared with placebo or control groups. [ABSTRACT FROM AUTHOR]

Aims: Whether sodium‐glucose co‐transporter 2 inhibitors are effective for heart failure caused by ATTR‐CA (transthyretin cardiac amyloidosis) remains uncertain. The aim of this study is to investigate the cardiovascular prognosis in ATTR‐CA mice model with dapagliflozin treatment. Methods and results: Humanized RBP4/TTRVal50Met and RBP4/TTR mice models were constructed with clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease (CRISPR‐Cas9) techniques and multiple generations breeding. A total of 6 RBP4/TTR mice received placebo treatment, when 12 RBP4/TTRVal50Met received dapagliflozin (1 mg/kg/day, 6 mice) and placebo (6 mice) treatment. Fasting glucose, intraperitoneal glucose tolerance test, and plasma brain natriuretic peptide (BNP) concentration were measured at Day 0, Week 2, and Week 4. BNP, transforming growth factor‐beta (TGF‐β), collagen type I alpha 1 (COL1A1) protein levels, and Cola1, TGFβ1, TNFα, IL‐1β, BNP relative quantities in cardiac, along with cardiac pathology examination including right ventricular collagen percentage, ventricular septum thickness, left ventricular wall thickness, and left ventricular internal diameter were measured at Week 4 after treatment procedure. All 18 mice completed the experiment. The baseline characteristics were balanced among three treatment groups. In placebo‐treated mice, the cardiac BNP relative quantity was significantly higher in RBP4/TTRVal50Met mice than RBP4/TTR mice (RBP4[KI/KI], TTR [KI/KI]: 0.72 ± 0.46, RBP4[KI/KI], TTRVal50Met[KI/KI]: 1.44 ± 0.60, P = 0.043), indicating more significant heart failure progression in ATTR‐CA mice than normal mice. In ATTR‐CA mice, the cardiovascular prognosis measurements including heart failure (plasma BNP concentration and relative quantities of BNP), cardiac inflammation (relative quantities of Cola1, TGFβ1, TNFα, and IL‐1β), and pathological changes (right ventricular collagen percentage, ventricular septum thickness, left ventricular wall thickness, and left ventricular internal diameter) were statistically comparable between those under dapagliflozin and placebo treatment. Conclusions: Dapagliflozin did not improve cardiovascular prognosis including the progression of heart failure, cardiac inflammation, and pathological changes in ATTR‐CA mice compared with placebo. The results of this study were not in support of dapagliflozin's therapeutic effects for ATTR‐CA. More pre‐clinical and clinical researches to validate these findings and demonstrate the underlying mechanisms are still required. [ABSTRACT FROM AUTHOR]

Aim: To assess the population attributable fractions (PAFs) for modifiable risk factors for microvascular complications of type 2 diabetes (T2D) in China. Materials and Methods: Data collected from the China National HbA1c Surveillance System from 2009 to 2013 were used. The PAFs of four predefined risk factors, including an HbA1c of 7% or higher, blood pressure (BP) of 130/80 mmHg or higher, low‐density lipoprotein‐cholesterol (LDL‐C) of 1.8 mmol/L or higher and body mass index (BMI) of 24 kg/m2 or higher, were calculated for diabetic microvascular complications, including diabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN). PAFs were further adjusted for age, sex and duration of diabetes. Results: In total, there were 998 379 participants with T2D from nationwide mainland China included in this analysis. As for DR, an HbA1c of 7% or higher, BP of 130/80 mmHg or higher, LDL‐C of 1.8 mmol/L or higher and BMI of 24 kg/m2 or higher conferred PAFs of 16.2%, 15.2%, 5.8% and 2.8%, respectively. In the case of DKD, BP of 130/80 mmHg or higher provided a PAF of 25.2%, followed by an HbA1c of 7% or higher (13.9%), BMI of 24 kg/m2 or higher (8.0%) and LDL‐C of 1.8 mmol/L or higher (5.6%). As for DSPN, an HbA1c of 7% or higher, BP of 130/80 mmHg or higher, LDL‐C of 1.8 mmol/L or higher and BMI of 24 kg/m2 or higher contributed to PAFs of 14.2%, 11.7%, 5.9% and 5.8%, respectively. PAFs for diabetic microvascular complications were mildly to moderately reduced after adjusting for participants' age, sex and duration of diabetes. Conclusions: Suboptimal glycaemic and BP control were the main contributors to diabetic microvascular complications, while the PAFs of unmet LDL‐C and BMI control targets were quite limited for diabetic microvascular complications. In addition to glycaemic control, BP control should be especially prioritized in the management of diabetic microvascular complications to further reduce the disease burden. [ABSTRACT FROM AUTHOR]

Photoinduced reactive oxygen species (ROS)‐based pollutant removal is one of the ideal solutions to achieve the conversion of solar energy into chemical energy and thus to address environmental pollution. Here, earth‐abundant CaCO3‐decorated g‐C3N4 (g‐C3N4 labeled as CN, CaCO3‐decorated g‐C3N4 sample labeled as CN‐CCO) has been constructed by a facile thermal polymerization method for safe and efficient photocatalytic NO removal. The decorated CaCO3 as "transit hub" extends the π bonds of CN to deviate from the planes and steers the random charge carriers, which thus provides extra active sites and expedites spatial charge separation to facilitate adsorption/activation of reactants and promote formation of ROS participating in the removal of pollutant. Furthermore, boosted generation of ROS regulates the photocatalytic NO oxidation pathway and thus increases the selectivity of products. NO prefers to be directly oxidized into final product (nitrate) rather than toxic intermediates (NO2), which is well demonstrated by theoretically simulated ROS‐based reaction pathways and experimental characterization. The present work promotes the degradation of pollutant and simultaneously suppresses the formation of toxic by‐product, which paves the way for ROS‐based pollutant removal. [ABSTRACT FROM AUTHOR]

Purpose: Diabetes mellitus (DM) is common among recipients of heart transplantation (HTx) but its impact on clinical outcomes is unclear. We evaluated the associations between pretransplant DM and posttransplant DM (PTDM) and outcomes among adults receiving HTx at a single center. Methods: We performed a retrospective study (range 01/2008 – 07/2018), n = 244. The primary outcome was survival; secondary outcomes included acute rejection, cardiac allograft vasculopathy, infection requiring hospitalization, macrovascular events, and dialysis initiation post‐transplant. Comparisons were performed using Kaplan‐Meier and multivariable Cox regression analyses. Results: Pretransplant DM was present in 75 (30.7%) patients and was associated with a higher risk for infection requiring hospitalization (p < 0.05), but not with survival or other outcomes. Among the 144 patients without pretransplant DM surviving to 1 year, 29 (20.1%) were diagnosed with PTDM at the 1‐year follow‐up. After multivariable adjustment, PTDM diagnosis at 1‐year remained associated with worse subsequent survival (hazard ratio 2.72, 95% confidence interval 1.03‐7.16). Predictors of PTDM at 1‐year included cytomegalovirus seropositivity and higher prednisone dose (> 5 mg/day) at 1‐year follow‐up. Conclusions: Compared to HTx recipients without baseline DM, those with baseline DM have a higher risk for infections requiring hospitalization, and those who develop DM after HTx have worse survival. [ABSTRACT FROM AUTHOR]

Intensified photocatalytic performance through reducing the recombination of electron–hole pairs and enhancing the oxidation capacity is a key challenge in the field of photocatalytic removal of volatile organic compounds (VOCs). Acetone, as one of the emblematical contaminants VOCs, is a general solvent and widely applied in the pharmaceutical industry, contributing severely to air pollution. Most studies of photocatalysis have focused on the photocatalyst efficiency toward pollutant degradation, but the detailed mechanisms of charge separation as well as transfer and photocatalytic acetone oxidation pathways are not revealed clearly. In this work, it is found that hafnium metal doping on the n‐type semiconductor SnO2 can modify the electronic structures, restrain the recombination of electron–hole pairs, where the hafnium metal ion acts as the activation site, leading to improved oxidation ability to realize efficient acetone degradation. In addition, the specific path toward the acetone degradation is revealed by closely combined active radical detection, in situ diffuse reflectance infrared Fourier transform spectroscopy and theoretical calculation methods. It provides a new perspective about the detailed and comprehensive reaction mechanism of photocatalytic acetone degradation and carriers transfer between pollutants and photocatalysts, which is expected to promote the practical usage of photocatalytic technology for the expeditious removal VOCs. [ABSTRACT FROM AUTHOR]

Aims: This meta‐analysis aimed to evaluate the risk of developing bullous pemphigoid (BP) and other skin‐related adverse events (AEs) in patients with type 2 diabetes (T2DM) undergoing dipeptidyl peptidase‐4 inhibitor (DPP‐4i) treatment in randomized controlled trials (RCTs). Methods: In this meta‐analysis, the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for RCTs, which involve patients with T2DM reporting skin‐related AEs. RCTs that comparatively evaluated the effects of DPP‐4i treatment and placebo on patients with T2DM and reported skin‐related AEs were included in the analysis. The odds ratio (OR) and 95% confidence interval (CI) were calculated using the Peto's methods. The GRADE approach was used to rate the quality of evidence. Results: A total of 46 randomized placebo‐controlled trials, including 3 trials with reports of BP (n = 38 011), that reported skin‐related AEs were included (n = 59 332). Compared to the placebo group, the risk of developing BP was significantly higher in the DPP‐4i treatment group (OR = 7.38, 95% CI 2.00‐27.25, I2 = 0%, P =.003; quality rating: very low). Additionally, DPP‐4i treatment was associated with an increased overall risk of developing skin‐related AEs (OR = 1.22, 95% CI 1.02‐1.46, I2 = 32%, P =.03; quality rating: moderate). Conclusions: This meta‐analysis suggested that treatment with DPP‐4is, including sitagliptin, saxagliptin, and linagliptin, was associated with an increased risk of developing BP. Additionally, the risk of developing skin‐related AEs increased when all DPP‐4is were combined. Skin lesion, especially BP, should be monitored in patients with diabetes undergoing DPP‐4i treatment. Future studies should evaluate the susceptible population and develop strategies for early detection of skin‐related AEs. [ABSTRACT FROM AUTHOR]

Background: Metformin is first‐line therapy for patients with diabetes. However, it may lower vitamin B12 concentrations, which could have hematological or neurological implications. This meta‐analyses reviewed all available studies on associations between metformin use and vitamin B12 levels, anemia, and neuropathy in diabetic patients. Methods: PubMed, Web of Knowledge, Cochrane Library, and Embase were searched to identify all relevant studies published in English prior to March 2018. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes and pooled mean differences (MDs) and 95% CIs were calculated for continuous outcomes. Results: Thirty‐one studies were included in the meta‐analyses. Compared with diabetic patients not taking metformin, patients taking metformin had a significantly higher risk of vitamin B12 deficiency (RR 2.09; 95% CI 1.49, 2.93; P < 0.0001; I2 = 64%) and significantly lower serum vitamin B12 concentrations (MD −63.70; 95% CI −74.35, −53.05] pM; P < 0.00001; I2 = 87%), which depended on dose and duration of treatment. Metformin use was also associated with significantly greater percentage decrease in serum vitamin B12 concentrations from baseline in diabetic patients (MD −14.68%; 95% CI −17.98%, −11.39%; P < 0.00001; I2 = 33%). Analyses revealed no significant association between metformin use and the prevalence of anemia or neuropathy. Conclusions: Metformin use led to significantly lowered vitamin B12 concentrations and significantly higher risk of vitamin B12 deficiency in diabetic patients. More quality studies are needed to explore the associations between metformin use and anemia and neuropathy in these patients. Annual vitamin B12 assessment in diabetic patients taking metformin is recommended. [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: To evaluate the efficacy and safety of combining insulin therapy with dipeptidyl peptidase‐4 (DPP‐4) inhibitors compared with combining insulin therapy with a placebo or other antihyperglycemic agents. Materials and Methods: A literature search was carried out via electronic databases. The inclusion criteria were randomized controlled trials comparing the addition of DPP‐4 inhibitors to insulin with the addition of a placebo or other active hypoglycemic agents to insulin therapy, study duration of no less than 12 weeks carried out in type 2 diabetes patients and the availability of outcome data to evaluate a change in the glycated hemoglobin. Results: The glycated hemoglobin‐lowering efficacy was significantly greater with DPP‐4 inhibitor/insulin (DPP‐4i/INS) than with placebo/insulin (weighted mean difference −0.53%, 95% confidence interval −0.63, −0.43, P < 0.01). The postprandial plasma glucose‐lowering efficacies was also significantly greater with DPP‐4i/INS than with placebo/insulin (weighted mean difference −1.65 mmol/L, 95% CI: −2.34, −0.96, P < 0.05). The risk of hypoglycemia or severe hypoglycemia was similar for DPP4i/INS and placebo/insulin treatments. There was no significant difference in the glycemia‐lowering efficacy between DPP‐4i/INS and alpha‐glucosidase inhibitors/insulin, thiazolidinedione/insulin and glucagon‐like peptide‐1 receptor agonist/insulin. Sodium–glucose cotransporter 2 inhibitor/insulin treatment achieved better placebo‐corrected efficacy in lowering postprandial plasma glucose, with less weight gain and no higher risk of hypoglycemia. Conclusions: Treatment with DPP‐4 inhibitors combined with insulin improved glycemic control without an increased risk of hypoglycemia or weight gain compared with insulin treatment alone. [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: To evaluate whether there is disparity of the efficacy and all‐cause mortality and other adverse effects between Asian and non‐Asian patients with sodium–glucose cotransporter 2 (SGLT2) inhibitors treatment. Materials and Methods: Randomized clinical trials publicly available before January 2017, comparing SGLT2 inhibitors treatment with a placebo in type 2 diabetes patients were identified. The association between treatment and outcomes was estimated by computing the weighted mean difference for glycated hemoglobin level, blood pressure level, lipid profile levels and bodyweight, and the odds ratios for adverse events. Results: A total of 17 trials with Asian patients were included and 39 trials with non‐Asian patients were included. Comparison of the glycated hemoglobin decreases corrected by a placebo between Asian and non‐Asian patients showed that there was a non‐significant difference of 0.05% between groups (P > 0.05). Comparisons of the bodyweight changes and blood pressure changes corrected by a placebo between Asian and non‐Asian patients did not show a significant difference between groups (P > 0.05). The risk of all‐cause mortality was not increased when compared with a placebo both in Asian and non‐Asian populations, and the risk of genital infection in Asian and non‐Asian populations were both significant increased. Conclusions: Overall, according to the present meta‐analysis, comparison of the efficacy in SGLT2 inhibitors treatment between Asian and non‐Asian type 2 diabetes patients showed no significant difference in glycated hemoglobin reduction and bodyweight reduction. Furthermore, no disparity was found in the risk of all‐cause mortality or hypoglycemia in SGLT2 inhibitors treatment between Asian and non‐Asian patients. [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: To evaluate the efficacy and safety of alpha‐glucosidase inhibitors (AGI) in Asian and non‐Asian type 2 diabetes patients. Materials and Methods: Studies were identified through a literature search of MEDLINE, EMBASE and other databases until December 2016. All statistical analyses were carried out in Review Manager statistical software by computing the weighted mean difference or odds ratio and 95% confidence interval. Results: A total of 67 studies were included. AGI vs placebo: compared with the placebo, AGI treatment led to a greater decrease in hemoglobin A1c (HbA1c), fasting plasma glucose and postprandial plasma glucose. No significant difference was observed in HbA1c change, fasting plasma glucose change, postprandial plasma glucose change or incidence of hypoglycemia between Asian and non‐Asian patients. AGI vs active controls: in Asian patients, AGI treatment showed a lower reduction in HbA1c compared with dipeptidyl peptidase‐4 inhibitors and sulfonylurea. In non‐Asian patients, AGI treatment showed a lower reduction in HbA1c compared with thiazolidinedione. No significant difference was observed in HbA1c change and bodyweight change when comparing AGI with other oral hypoglycemic agents between Asian and non‐Asian patients. Conclusions: The effects of AGI treatment on glycemic control and bodyweight reduction were superior to the placebo without an increased incidence of hypoglycemia, but with an increased incidence of gastrointestinal discomforts. The hypoglycemic effects of AGI were comparable between Asian and non‐Asian patients. [ABSTRACT FROM AUTHOR]

Objective: Sodium glucose cotransporter 2 (SGLT2) inhibitors may induce urinary glucose excretion via the inhibition of renal glucose reabsorption, improve glycemic control, and lower body weight. The aim of this meta-analysis was to evaluate weight changes in patients who received different dosages of SGLT2 inhibitors.Methods: Overall, 55 placebo-controlled trials were included.Results: The results indicated that treatment with 2.5 mg, 5 mg, 10 mg, and 20 mg of dapagliflozin led to significant decreases in body weight compared with a placebo (weighted mean difference [WMD], -1.30 kg, -1.51 kg, -1.79 kg, -2.24 kg, respectively; P < 0.001). Treatment with 50 mg, 100 mg, 200 mg, and 300 mg of canagliflozin also led to significant decreases in weight (WMD, -1.20 kg, -1.82 kg, -1.83 kg, -2.37 kg, respectively; P < 0.001). In the treatment with empagliflozin, ipragliflozin, tofogliflozin, and luseogliflozin, body weight also significantly decreased. The decrease in weight was associated with the dosage of dapagliflozin (P < 0.05).Conclusions: Body weight significantly decreased in patients with type 2 diabetes who received different dosages of SGLT2 inhibitors compared with patients who received a placebo. Moreover, in patients treated with dapagliflozin, there was a statistically significant dosage-dependent trend in body weight reduction. [ABSTRACT FROM AUTHOR]

Aims/Introduction To evaluate the efficacy of weight changes from baseline of the sodium-glucose cotransporter 2 (SGLT2) inhibitors treatment and glucagon-like peptide-1 (GLP-1) analogs treatment after comparisons with a placebo in type 2 diabetes patients, and the associated factors. Materials and Methods Studies were searched from when recording began, June 2004, until June 2015, and re-searched in July 2016, and placebo-controlled randomized trials in type 2 diabetes patients with a study length of ≥12 weeks were included. Results A total of 97 randomized controlled trials were included. Compared with a placebo, treatment with SGLT2 inhibitors was associated with a significantly greater decrease in weight change from baseline (weighted mean differences −2.01 kg, 95% confidence interval −2.18 to −1.83 kg, P < 0.001). Compared with a placebo, changes with GLP -1 treatment were also associated with a comparable decrease in weight change from baseline (weighted mean differences −1.59 kg, 95% confidence interval −1.86 to −1.32 kg, P < 0.001). Meta-regression analysis showed that the baseline age, sex, baseline glycated hemoglobin, diabetes duration or baseline body mass index were not associated with the weight change from baseline in SGLT2 inhibitors or in GLP-1 treatment corrected by placebo. Comparisons of weight changes from baseline corrected by placebo between SGLT2 inhibitors and GLP-1 treatment showed that the difference was not significant ( P > 0.05). Conclusions According to the present meta-analysis, treatment with SGLT2 inhibitors and treatment with GLP-1 analogs led to comparable weight changes from baseline, which are both with significance when compared with placebo treatment. [ABSTRACT FROM AUTHOR]

Background: To evaluate the risk of infections in the treatment of type 2 diabetes patients with dipeptidyl-peptidase 4 (DPP-4) inhibitors.Methods: A literature search was conducted through electronic databases. The inclusion criteria included study duration of no less than 12 weeks developed in type 2 diabetes patients, the use of a randomized control group receiving a DPP-4 inhibitor and the availability of outcome data for infections. Out of 2181 studies, 74 studies were finally included.Results: The risk of overall infection for DPP-4 inhibitors treatment was comparable to placebo (odds ratio (OR) = 0.97, 95% confidence interval (CI), 0.91 to 1.04, p = 0.40), metformin treatment (OR = 1.22, 95% CI, 0.95 to 1.56, p = 0.12), sulphonylurea treatment (OR = 1.09, 0.93 to 1.29, p = 0.29), thiazolidinedione treatment (OR = 0.86, 95% CI, 0.65 to 1.14, p = 0.29) and alpha glucosidase inhibitor treatment (OR = 1.03, 95% CI, 0.33 to 3.22, p = 0.96). When compared different DPP-4 inhibitors with placebo treatment, risks of infections were comparable for alogliptin, linagliptin, sitagliptin, saxagliptin and vildagliptin. Compared with placebo or active comparator treatment, risks of infection in different systems for DPP-4 inhibitors were all comparable.Conclusions: The overall risk of infections of DPP-4 inhibitor was not increased compared with control groups. [ABSTRACT FROM AUTHOR]

Background: Despite significant advances in durable mechanical support survival, infectious complications remain the most common adverse event after ventricular assist device (VAD) implantation and the leading cause of early death after transplantation. In this study, we aim to describe our local infectious epidemiology and review short‐term survival and infectious incidence rates in the post‐transplantation period and assess risk factors for infectious episodes after transplantation. Methods: Retrospective single‐center study of all consecutive adult heart transplant patients from 2008 to 2017. Survival data were estimated and summarized using the Kaplan‐Meier method. We quantified and evaluated the difference in the incidence rate between patients with and without infection using a Fine‐Gray model. The outcome of interest is the time to first infection diagnosis with post‐transplant death as the competing event. Results: Among 278 heart transplant patients, 74 (26.5%) underwent LVAD implantation. Twenty‐one patients (28.3%) developed an infection while supported by an LVAD. When compared to patients supported by an LVAD without a preceding infection, BMI was significantly greater (31.2 vs 27.8 kg/m2, P = .03). Median follow‐up post‐transplantation was 3.01 years. Significant risk factors for the competing risk regression for infection after heart transplantation include LVAD infection (HR 1.94, [95% CI] 1.11‐3.39, P = .020) and recipient COPD (HR 2.14, [95% CI] 1.39‐3.32, P = .001) when adjusted for recipient age, gender, hypertension, diabetes mellitus, and body mass index. Conclusions: Patients with LVAD‐related infection had a significantly increased risk of infectious complications after heart transplantation. Further research on the avoidance of induction agents and reduced maintenance immunosuppression in this patient population is warranted. [ABSTRACT FROM AUTHOR]

Background: Two or more different epidermal growth factor receptor (EGFR) mutations can be detected within a single tumor sample, which represents complex mutations. However, the frequency and efficacy of tyrosine kinase inhibitor (TKI) treatments for patients harboring these mutations are unknown.Methods: From January 2011 to January 2017, patients diagnosed with EGFR mutations were screened. The effectiveness of TKIs in patients with complex mutations was retrospectively analyzed.Results: A total of 16,840 subjects were screened, and there were 5898 positive patients. One hundred eighty-seven patients (3.2% of all patients with EGFR mutations) had complex EGFR mutations, and 51 of the patients with advanced adenocarcinoma were treated with TKIs as a first-line treatment. The objective response rates for patients who had Del-19+21L858R mutations (n = 15), Del-19/21L858R+atypical mutations (n = 16), double atypical mutations (n = 8), and complex mutations with a primary drug-resistant pattern (n = 12) were 75.0%, 60.0%, 71.0%, and 8.3%, respectively. The median progression-free survival times for the 4 groups were 18.2 months (95% confidence interval [CI], 10.6-25.9 months), 9.7 months (95% CI, 3.3-15.8 months), 9.6 months (95% CI, 3.3-19.0 months), and 1.4 months (95% CI, 0.4-2.3 months), respectively.Conclusions: These results from the largest sample size suggest that EGFR-TKI therapy is effective in patients with Del-19+21L858R mutations, Del-19/21L858R+atypical mutations, and double atypical mutations but is less effective in patients with a primary drug-resistant pattern. Patients with the Del-19+21L858R mutations may, therefore, benefit more from treatment with first-generation TKIs. Cancer 2018;124:2399-406. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have shown their beneficial effects on cardiovascular outcomes and multiple cardiovascular risk factors, including hypertension. However, the mechanism of blood pressure (BP)-lowering effects of these agents has not been elucidated. This study aims to evaluate the effect of hemoglobin A1c reduction or body weight reduction with GLP-1RA treatment and SGLT2i treatment on BP changes in patients with type 2 diabetes mellitus. Methods and Results Studies were identified by a search of MEDLINE, EMBASE, and the Cochrane Central Register until June 2019. Meta-regression analysis was performed to evaluate the association between hemoglobin A1c reduction or body weight reduction and changes of BP. A total of 184 trials were included. Both GLP-1RA and SGLT2i led to significant reductions in systolic BP (weighted mean difference, -2.856 and -4.331 mm Hg, respectively; P <0.001 for both) and diastolic BP (weighted mean difference, -0.898 and -2.279 mm Hg, respectively; P <0.001 for both). For both drug classes, hemoglobin A1c reduction was not independently associated with systolic BP reduction or diastolic BP reduction. In GLP-1RA treatment, weight reduction was positively associated with systolic BP reduction and diastolic BP reduction (β=0.821 and β=0.287, respectively; P <0.001 for both). In SGLT2i treatment, weight loss was significantly associated with systolic BP reduction (β=0.820; P =0.001) but was not associated with diastolic BP reduction. Conclusions Treatment with GLP-1RA and SGLT2i led to significant reductions in BP in patients with type 2 diabetes mellitus. Weight reduction was significantly and independently associated with BP reductions in GLP-1RA treatment and SGLT2i treatment.