IMPORTANCE Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been widely recommended for glucose control and cardiovascular risk reduction in patients with type 2 diabetes, and more recently, for weight loss. However, the associations of GLP-1 RAs with gallbladder or biliary diseases are controversial.OBJECTIVE To evaluate the association of GLP-1 RA treatment with gallbladder and biliary diseases and to explore risk factors for these associations.DATA SOURCES MEDLINE/PubMed, EMBASE, Web of Science, and Cochrane Library (inception to June 30, 2021), websites of clinical trial registries (July 10, 2021), and reference lists. There were no language restrictions. STUDY SELECTION Randomized clinical trials (RCTs) comparing the use of GLP-1 RA drugs with placebo or with non−GLP-1 RA drugs in adults.DATA EXTRACTION AND SYNTHESIS Two reviewers independently extracted data according to the PRISMA recommendations and assessed the quality of each study with the Cochrane Collaboration risk-of-bias tool. Pooled relative risks (RRs) were calculated using random or fixed-effects models, as appropriate. The quality of evidence for each outcome was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. MAIN OUTCOMES AND MEASURESThe primary outcome was the composite of gallbladder or biliary diseases. Secondary outcomes were biliary diseases, biliary cancer, cholecystectomy, cholecystitis, and cholelithiasis. Data analyses were performed from August 5, 2021, to September 3, 2021.RESULTS A total of 76 RCTs involving 103 371 patients (mean [SD] age, 57.8 (6.2) years; 41 868 [40.5%] women) were included. Among all included trials, randomization to GLP-1 RA treatment was associated with increased risks of gallbladder or biliary diseases (RR, 1.37; 95% CI, 1.23-1.52); specifically, cholelithiasis (RR, 1.27; 95% CI, 1.10-1.47), cholecystitis (RR, 1.36; 95% CI, 1.14-1.62), and biliary disease (RR, 1.55; 95% CI, 1.08-2.22). Use of GLP-1 RAs was also associated with increased risk of gallbladder or biliary diseases in trials for weight loss (n = 13; RR, 2.29; 95% CI, 1.64-3.18) and for type 2 diabetes or other diseases (n = 63; RR, 1.27; 95% CI, 1.14-1.43; P <.001 for interaction). Among all included trials, GLP-1 RA use was associated with higher risks of gallbladder or biliary diseases at higher doses (RR, 1.56; 95% CI, 1.36-1.78) compared with lower doses (RR, 0.99; 95% CI, 0.73-1.33; P = .006 for interaction) and with longer duration of use (RR, 1.40; 95% CI, 1.26-1.56) compared with shorter duration (RR, 0.79; 95% CI, 0.48-1.31; P = .03 for interaction).CONCLUSIONS AND RELEVANCE This systematic review and meta-analysis of RCTs found that use of GLP-1 RAs was associated with increased risk of gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss.
Highlights: Definitive RT/CRT for OSCC achieved acceptable rate of locoregional control. Definitive RT is a reasonable alternative treatment strategy if surgery is not possible. cN2-3 is associated with poor distant control, DFS, and OS.
Objective This study aimed to systematically evaluate the association between triceps skinfold (TSF) thickness (which indicates subcutaneous fat) mid‐arm muscle circumference (MAMC; which reflects muscle mass), mid‐upper arm circumference (MUAC), and all‐cause mortality. Methods A total of 17,717 adults from the China Health and Nutrition Survey (1993‐2015) were included. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all‐cause mortality. The joint effect of TSF thickness and MAMC was examined, and planned subgroup analyses were performed. Results The highest quartiles of TSF thickness, MAMC, and MUAC were significantly associated with low all‐cause mortality, independent of BMI (TSF thickness: HR = 0.704 [95% CI: 0.575‐0.862]; MAMC: HR = 0.729 [95% CI: 0.607‐0.876]; MUAC: HR = 0.713 [95% CI: 0.583‐0.872]). A 1‐SD increase showed comparable risk reductions for TSF thickness and MAMC (14.6% and 14.0%), with 16.1% risk reductions in MUAC. There were positive additive interactions between TSF thickness and MAMC. The inverse association existed in young, middle‐aged, and elderly participants (P‐heterogeneity > 0.05). Conclusions Mid‐arm muscle and subcutaneous fat were inversely associated with all‐cause mortality, independent of BMI, beyond the elderly population. Mid‐arm muscle and subcutaneous fat made comparable contributions to and had positive joint effects on all‐cause mortality.
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