Background Preclinical studies have suggested potential beneficial effects of newer glucose‐lowering drugs (GLDs) including dipeptidyl peptidase (DPP)‐4 inhibitors, glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), and sodium glucose co‐transporter‐2 (SGLT2) inhibitors, in protecting humans against cognitive decline and dementia. However, population studies aiming to demonstrate such cognitive benefits from newer GLDs have produced mixed findings. This meta‐analysis aimed to evaluate the association between newer GLDs and risk of dementia in adults with type 2 diabetes (T2D). Methods Electronic databases were searched up to March 11, 2022 to include observational studies that examined the association between DPP‐4 inhibitors, GLP‐1RAs, and SGLT2 inhibitors and risk of dementia (including all‐cause dementia, Alzheimer's disease [AD], and vascular dementia [VD]) in people with T2D. We conducted a random‐effects meta‐analysis to calculate the relative risk (RR) with 95% confidence interval (CI) for each class of newer GLD. Results Ten studies (from nine articles) involving 819,511 individuals with T2D were included. Three studies found that SGLT2 inhibitor users had a lower risk of all‐cause dementia than non‐SGLT2 inhibitor users (RR, 0.62; 95% CI, 0.39–0.97). Five studies found that users versus nonusers of GLP‐1RAs were associated with a significant reduction in the risk of all‐cause dementia (RR, 0.72; 95% CI, 0.54–0.97). However, a meta‐analysis for AD and VD was unavailable for SGLT2 inhibitors and GLP‐1RAs because only one study was included for each drug. In seven studies, users vs. nonusers of DPP‐4 inhibitors were significantly associated with a decreased risk of all‐cause dementia (RR, 0.84; 95% CI, 0.74–0.94) and VD (RR, 0.59; 95% CI, 0.47–0.75) but not AD (RR, 0.82; 95% CI, 0.63–1.08). Conclusion Newer GLDs were associated with a decreased risk of all‐cause dementia in people with T2D. Because of the observational nature and significant heterogeneity between studies, the results should be interpreted with caution. Further research is warranted to confirm our findings.
Incidence of cutaneous malignant melanoma has continued to rise despite public efforts to promote sun protection behaviors among populations at risk. However, dietary factors may also affect the development of melanoma. In the past few decades, findings from epidemiologic and experimental research have linked consumption of several foods and other nutrients to the risk of melanoma. Caffeine has been associated with a lower risk of melanoma, and citrus fruits and alcohol with increased risk. Associations between polyunsaturated fatty acid, niacin/nicotinamide, folate, and vitamin D with melanoma remain controversial. Diet likely influences melanoma development through several potential mechanisms, such as enhancing UV-induced apoptosis and increasing photosensitivity. We conducted a narrative review to summarize recent epidemiologic studies of diet and melanoma based on published literature. Given the high prevalence of the food items and nutrients covered in this review and the decades-long rising melanoma incidence worldwide, the associations we discuss may have important public health implications in terms of reducing melanoma incidence through dietary modification. .
The methylenetetrahydrofolate reductase () C677T gene polymorphism has been suggested to be associated with the risk of essential hypertension (EH), however, results remain inconclusive. To investigate this association, the present meta-analysis of 27 studies including 5,418 cases and 4,997 controls was performed. The pooled odds ratio (OR) and its corresponding 95% confidence interval were calculated using the random-effects model. A significant association between the C677T gene polymorphism and EH was found under the allelic (OR, 1.32; 95% CI, 1.20-1.45; P=0.000), dominant (OR, 1.39; 95% CI, 1.25-1.55; P=0.000), recessive (OR, 1.38; 95% CI, 1.18-1.62; P=0.000), homozygote (OR, 1.59; 95% CI, 1.32-1.92; P=0.000), and heterozygote (OR, 1.32; 95% CI, 1.20-1.45; P=0.000) genetic models. A strong association was also revealed in subgroups, including Asian, Caucasian and Chinese. The Japanese subgroup did not show any significant association under all models. Meta-regression analyses suggested that the study design was a potential source of heterogeneity, whereas the subgroup analysis additionally indicated that the population origin may also be an explanation. Another subgroup analysis revealed that hospital-based studies have a stronger association than population-based studies, however, the former suffered a greater heterogeneity. Funnel plot and Egger's test manifested no evidence of publicationbias. In conclusion, the present study supports the evidence for the association between the C677T gene polymorphism and EH in the whole population, as well as in subgroups, such as Asian, Caucasian and Chinese. The carriers of the 677T allele are susceptible to EH.
Purpose: This study aimed to systematically evaluate the association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and pancreatic safety in patients with type 2 diabetes mellitus (T2DM).Methods: Electronic databases were searched before September 2019 to include randomized controlled trials (RCTs) of SGLT2 inhibitors that reported any event on pancreatitis or pancreatic cancer among patients with T2DM. Peto odds ratio (OR) with 95% confidence interval (CI) was used to pool the data. The GRADE framework was introduced to assess the quality of evidence. Results: Of the 35 trials involving 44 912 patients with T2DM included, 41 events of acute pancreatitis (19 trials; 32 932 patients), 72 events of overall pancreatitis (including acute pancreatitis, chronic pancreatitis, or nonspecific pancreatitis; 26 trials; 36 688 patients), and 40 events of pancreatic cancer (18 trials; 27 806 patients) werereported during a median follow-up of 52 weeks. SGLT2 inhibitors were not associated with an increased risk of acute pancreatitis compared to controls (placebo or other active drugs; Peto OR, 1.13; 95% CI, 0.60-2.13; moderate quality evidence). A similar result was found for risk of overall pancreatitis (Peto OR, 1.08; 95% CI, 0.67-1.75; moderate quality evidence) and pancreatic cancer (Peto OR, 1.34; 95% CI, 0.71-2.54; very low-quality evidence).Conclusions: Moderate quality evidence from RCTs shows no significantly increased risk of acute pancreatitis associated with SGLT2 inhibitors, while there is very lowquality evidence suggesting no significant association between SGLT2 inhibitors and pancreatic cancer among patients with T2DM. K E Y W O R D Sacute pancreatitis, meta-analysis, pancreatic cancer, pharmacoepidemiology, SGLT2 inhibitors, type 2 diabetes
SummaryIt has been reported that sodium‐glucose cotransporter 2 (SGLT2) inhibitors could increase blood viscosity, which may further increase risk of venous thromboembolism (VTE). Therefore, we conducted this meta‐analysis to evaluate the association between SGLT2 inhibitors and risk of VTE in patients with type 2 diabetes. We systematically searched electronic databases up to April 2019 to identify randomized trials that reported the events of VTE in SGLT2 inhibitors group and control group (placebo or other active antidiabetic drugs). The primary outcome was VTE, and secondary outcomes included deep venous thrombosis (DVT) and pulmonary embolism (PE). A fixed‐effects meta‐analysis was performed to calculate the risk ratio (RR) with 95% CI. In total, 29 randomized trials involving 56 035 patients with type 2 diabetes were included. Incidence of VTE was not significantly different between SGLT2 inhibitors group and control group (128/32 038 vs 92/23 997), yielding an RR of 0.98 (95% CI, 0.75‐1.28). Similarly, null associations were observed in the subgroup analyses. Our cumulative meta‐analysis demonstrated the stability of our overall result over time. There was no significant association between SGLT2 inhibitors and risk of both DVT (17 trials; 31/17 442 vs 15/10 930; RR, 1.06; 95% CI, 0.60‐1.89) and PE (19 trials; 56/26 118 vs 41/19 517; RR, 0.99; 95% CI, 0.67‐1.46). Low statistical heterogeneity and no evidence of publication bias were observed. Current evidence from randomized trials found no association between SGLT2 inhibitors and risk of VTE among patients with type 2 diabetes.
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