Lower risk of gout in sodium glucose cotransporter 2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors in type-2 diabetes.

OBJECTIVES: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) vs dipeptidyl peptidase-4 inhibitors (DPP4I) on the risk of new-onset gout remains unknown. This study aims to compare the effects of SGLT2I against DPP4I on gout risks. METHODS: This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus treated with SGLT2I or DPP4I between 1 January 2015 and 31 December 2020 in Hong Kong. The study outcomes are new-onset gout and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I was performed. Univariable and multivariable Cox regression models were conducted. Competing risks models and multiple approaches based on the propensity score were applied. RESULTS: This study included 43 201 patients [median age: 63.23 years old (Interquartile range, IQR): 55.21-71.95, 53.74% males; SGLT2I group: n = 16 144; DPP4I group: n = 27 057] with a median follow-up of 5.59 years (IQR: 5.27-5.81 years) since initial drug exposure. The incidence rate of developing gout [Incidence rate (IR): 2.5; 95% CI: 2.2, 2.9] among SGLT2I users was significantly lower than DPP4I users (IR: 5.2; 95% CI: 4.8, 5.8). SGLT2I was associated with 51% lower risks of gout (HR: 0.49; 95% CI: 0.42, 0.58; P-value < 0.0001) and 51% lower risks of all-cause mortality (HR: 0.49; 95% CI: 0.42, 0.58; P-value < 0.0001) after adjusting for significant demographics, past comorbidities, medications and laboratory results. The results remained consistent on competing risk and other propensity score approaches. CONCLUSIONS: SGLT2I use was associated with lower risks of new gout diagnosis compared with DPP4I use.

Effectiveness of Taijiquan in treating insomnia: A systematic review and meta-analysis of randomized controlled studies.

Background: Sleep efficiency of <80% based on actigraphy was defined as insomnia as self-reported difficulty falling asleep or waking up at night three to four times per week. It is known that adequate sleep is very important for human wellbeing, affecting people's work and life, insomnia will seriously damage our daily life. There is no recognized non-drug treatment. Studies have found that Taijiquan has a positive effect on insomnia patients. This systematic review and meta-analysis will evaluate the effect of Taijiquan on insomnia. Methods: To find all randomized controlled trials exploring the effects of Taijiquan on insomnia patients in Chinese and English, eight databases (Pubmed, Embase, Cochrane library, Web of Science, CNKI, CBM, VIP, and Wanfang Data) were searched. The retrieval time is from database construction to October 2021. Searches were conducted in both English and Chinese language. A meta-analysis by mean difference (MD) and 95% confidence interval (CI) was performed with RevMan 5.3. The risk of bias for each study was accounted for according to the Cochrane Handbook. Our primary outcome was Pittsburg Sleep Quality Index. We explored sources of heterogeneity by comparing effect sizes across different types of etiology, country, control group, and intervention type. The protocol was pre-registered with PROSPERO, CRD42021284511. Results: Twenty-one RCTs published between 2004 and 2021 with 2,022 participants were included in this study. Twenty-one randomized controlled studies showed that Tai Chi significantly improved PSQI scores in patients with cancer, muscle fibrosis, and sub-health insomnia [MD = -1.16, 95% CI (-1.62, -0.71), P < 0.01]; There is insufficient evidence of improvement in patients with cerebrovascular disease [MD = -0.54, 95% CI (-1.58, 0.51), P = 0.31]; 8-form, 10-form or 24-form Yang's Taijiquan had the same effect in improving PSQI [MD = -1.33, 95% CI (-1.85, -0.81), P < 0.01]. When there is no treatment, exercise, exercise and health education as the control, taijiquan has a significant effect on insomnia treatment, and there is no difference in efficacy compared with cognitive behavioral therapy and health education (usual care) alone. Conclusions: The results of the study showed that Taijiquan significantly improved sleep quality in healthy adults and patients with chronic diseases, which suggests that Taijiquan may be considered as an alternative behavioral therapy in the treatment of insomnia. In the future, more high-quality, well-controlled randomized trials are needed to better inform clinical decisions.

Risk of New-Onset Prostate Cancer for Metformin Versus Sulfonylurea Use in Type 2 Diabetes Mellitus: A Propensity Score-Matched Study.

BACKGROUND: The aim of this study was to compare the risks of new-onset prostate cancer between metformin and sulfonylurea users with type 2 diabetes mellitus (T2DM). METHODS: This population-based retrospective cohort study included male patients with T2DM presenting to public hospitals/clinics in Hong Kong between January 1, 2000, and December 31, 2009. We only included patients prescribed either, but not both, metformin or sulfonylurea. All patients were followed up until December 31, 2019. The primary outcome was new-onset prostate cancer and the secondary outcome was all-cause mortality. One-to-one propensity score matching was performed between metformin and sulfonylurea users based on demographics, comorbidities, antidiabetic and cardiovascular medications, fasting blood glucose level, and hemoglobin A1c level. Subgroup analyses based on age and use of androgen deprivation therapy were performed. RESULTS: The final study cohort consisted of 25,695 metformin users (mean [SD] age, 65.2 [11.8] years) and 25,695 matched sulfonylurea users (mean [SD] age, 65.3 [11.8] years) with a median follow-up duration of 119.6 months (interquartile range, 91.7-139.6 months) after 1:1 propensity score matching of 66,411 patients. Metformin users had lower risks of new-onset prostate cancer (hazard ratio, 0.80; 95% CI, 0.69-0.93; P=.0031) and all-cause mortality (hazard ratio, 0.89; 95% CI, 0.86-0.92; P<.0001) than sulfonylurea users. Metformin use was more protective against prostate cancer but less protective against all-cause mortality in patients aged <65 years (P for trend <.0001 for both) compared with patients aged ≥65 years. Metformin users had lower risk of all-cause mortality than sulfonylurea users, regardless of the use of androgen deprivation therapy (P for trend <.0001) among patients who developed prostate cancer. CONCLUSIONS: Metformin use was associated with significantly lower risks of new-onset prostate cancer and all-cause mortality than sulfonylurea use in male patients with T2DM.

Cell-permeable Tat-NBD peptide attenuates rat pancreatitis and acinus cell inflammation response.

AIM: To investigate the effects of Tat-NEMO-binding domain (NBD) peptide on taurocholate-induced pancreatitis and lipopolysaccharide (LPS)-stimulated AR42J acinus cells inflammatory response in rats. METHODS: Sodium taurocholate (5%) was used to induce the pancreatitis model. Forty-eight rats from the taurocholate group received an intravenous bolus of 13 mg/kg Tat-NBD (wild-type, WT) peptide, Tat-NBD (mutant-type, MT) peptide, NBD peptide or Tat peptide. The pancreatic histopathology was analyzed by hematoxylin staining. LPS was added to the culture medium to stimulate the AR42J cells. For pretreatment, cells were incubated with different peptides for 2 h before LPS stimulation. Expression of IL-1beta and TNF-alpha mRNA was analyzed using a semi-quantitative reverse-transcript polymerase chain reaction (RT-PCR) method. IL-1beta and TNF-alpha protein in culture medium were detected by enzyme linked immunosorbent assay (ELISA). NF-kappaB DNA-binding in pancreas was examined by electrophoretic mobility shift assays. P65 expression of AR42J was determined by Strept Actividin-Biotin Complex (SABC) method. RESULTS: Pretreatment with Tat-NBD (WT) peptide at a concentration of 13 mg/kg body wt showed beneficial effect in pancreaitis model. LPS (10 mg/L) resulted in an increase of IL-1beta mRNA, IL-1beta protein, TNF-alpha mRNA and TNF-alpha protein, whereas significantly inhibitory effects were observed when cells were incubated with Tat-NBD (WT). Consisting with p65 expression decrease analyzed by SABC method, NF-kappaB DNA-binding activity significantly decreased in Tat-NBD (WT) pretreatment group, especially at the largest dose. No significant changes were found in the control peptide group. CONCLUSION: Our result supports that active NF-kappaB participates in the pathogenesis of STC-induced acute pancreatitis in rats. Tat-NBD (WT) peptide has anti-inflammatory effects in this model and inhibits the inflammation of acinus simulated by LPS.