Objectives: To evaluate the risk of cancers of digestive system with incretin-based therapies among patients with type 2 diabetes mellitus. Research design and methods: Medline, Embase, Cochrane Library and ClinicalTrials.gov databases were searched for randomized controlled clinical trials that compared incretin-based drugs with placebo or other antidiabetic drugs. Paired reviewers independently screened citations, extracted data and assessed risk of bias of included studies. Network meta-analysis was performed, followed by subgroup analysis. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence. Results: A total of 84 studies (n=101 595) involving cancers of digestive system were identified (a median follow-up of 30 weeks). The risk of cancers of digestive system with incretin-based therapies was comparable with insulin (OR: 0.86, 95% CI 0.27 to 2.69), metformin (OR: 0.32, 95% CI 0.07 to 1.38), sodium-glucose co-transporter 2 (OR: 5.26, 95% CI 0.58 to 47.41), sulfonylureas (OR: 1.27, 95% CI 0.68 to 2.39), thiazolidinediones (OR: 0.42, 95% CI 0.13 to 1.42), alpha-glucosidase inhibitors (OR: 2.98, 95% CI 0.12 to 73.80), and placebo (OR: 0.87, 95% CI 0.71 to 1.05). The results of subgroup analysis based on the type of digestive system cancers indicated that incretin-based therapies did not increase the risk of gastrointestinal cancers, respectively. The results of subgroup analysis based on age, duration, mean HbA1c, trial duration, and sample size did not indicate the risk of digestive system cancers. Conclusions: Moderate to high Grading of Recommendations Assessment, Development and Evaluation evidence suggests that incretin-based therapies were not associated with an increased risk of cancer of digestive system in patients with type 2 diabetes mellitus.

Purpose: To evaluate the effects of serum thyroid hormone levels on advanced liver fibrosis in cases with NAFLD (non-alcoholic fatty liver disease) and T2DM (type 2 diabetes mellitus). Patients and Methods: A total of 1422 cases with T2DM who were admitted to Peking University International Hospital between December 2014 and October 2019 were retrospectively analyzed. Standard anthropometry as well as clinical and laboratory evaluation were performed on all patients. Abdominal ultrasonography was performed to diagnose NAFLD. NFS (NAFLD fibrosis score) was used to identify advanced fibrosis in patients with T2DM and NAFLD. Results: In cases with T2DM and NAFLD, the serum FT3 level in cases with advanced fibrosis was lower than that in those without advanced fibrosis (4.79± 0.89 vs 4.28± 1.19, P < 0.05), and significant difference was not found in serum levels of FT4 and TSH between cases with advanced fibrosis and those without advanced fibrosis (P > 0.05). The incidence of advanced fibrosis declined as the rise of serum FT3 levels (P _trend < 0.05). Besides, FT3 (OR, 0.492; 95% CI, 0.384– 0.631) was noted as a factor influencing advanced fibrosis in cases with T2DM and NAFLD (P< 0.05). Conclusion: In cases with T2DM and NAFLD, the incidence of advanced fibrosis is negatively correlated with serum FT3 levels, and a low FT3 level is an independent risk factor of advanced fibrosis.

Aims/introduction: Cognitive dysfunction, including mild cognitive impairment and dementia, is increasingly recognized as an important complication of type 2 diabetes mellitus. The aims of the preset study was to investigate the cognitive protection of incretin‐based therapies, including glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors, in patients with type 2 diabetes mellitus.Materials and Methods: PubMed, EMBASE, Cochrane library, Web of Science and PsycINFO were searched from the inception through 17 January 2023 for randomized controlled trials and cohort studies on the association between incretin‐based therapies and cognitive function. A total of 15 studies were finally included in our systematic review, and eight of which were incorporated into our meta‐analysis.Results: Pooled results showed that the Mini‐Mental State Examination score in incretin‐based therapy groups was increased by 1.20 compared with the control group (weighted mean difference 1.20, 95% confidence interval 0.39–2.01). The results of eight studies assessed by the Newcastle Ottawa Quality Assessment Scale and the Cochrane Collaboration's tool, and the quality of the eight studies were at a relatively high level. Egger's regression did not show significant publication bias.Conclusions: Current evidence shows that incretin‐based therapies might be more effective, when compared with the other hypoglycemic drugs, for cognitive improvement in patients with type 2 diabetes mellitus.

Background: The objective was to evaluate the efficacy of the combination of Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), dipeptidyl peptidase‐4 inhibitors (DPP‐4i), and sodium‐glucose cotransporter 2 inhibitor (SGLT‐2i) in the treatment of Type 2 diabetes with poor efficacy of basic insulin and metformin/sulfonylurea by umbrella review.Materials and Methods: Forming the data of publication of each database through 13 September 2022, PubMed, EMBASE, and Cochrane Library were surveyed.Results: A total of seven meta‐analyses were included in the umbrella review. The combination of GLP‐1 RA (WMD −3.41 [−5.61, −1.21], p = 0.002), SGLT‐2i (WMD −5.34 [−9.56, −1.13], p = 0.013), and DPP‐4i (WMD −5.56 [−7.39, −3.73], p ≤ 0.001) can significantly reduce HbA1c levels, respectively. The combination of GLP‐1 RA (WMD −1.55 [−2.92, −0.18], p = 0.027), SGLT‐2i (WMD −2.96 [−6.68, 0.77], p = 0.12), and DPP‐4i (WMD −2.05 [−2.82, −1.28], p ≤ 0.001) can significantly reduce fasting plasma glucose (FPG) levels, respectively. The combination of GLP‐1 RA (WMD −3.24 [−5.14, −1.34], p < 0.001) can significantly reduce body weight of Type 2 diabetes mellitus (T2DM). The dose of basic insulin in diabetes patients after combined use of GLP‐1 RA (WMD −2.74 [−4.26, −1.22], p ≤ 0.001) was significantly reduced. The combination use of GLP‐1 RAs (OR 1.28 [1.05, 1.56], p = 0.017) increases the risk of hypoglycemia.Conclusions: The combination of GLP‐1 RAs, DPP‐4i, and SGLT‐2i can effectively lower HbA1c and FPG in T2DM patients who have poor therapeutic effects on basic insulin combined with metformin/sulfonylureas, respectively. Compared to placebo, GLP‐1 RAs can significantly reduce body weight and basic insulin dosage, while DPP‐4i and SGLT‐2i have a lower risk of hypoglycemia.Trial Registration:CRD42023410345.

Background The aim of the present study was to investigate alterations in the plasma level of coupling factor 6 (CF6), a novel endogenous inhibitor of prostacyclin, in patients with coronary heart disease. Methods and Results In total, 35 patients with coronary heart disease and 20 age-matched healthy subjects were examined. Plasma levels of CF6 and 6-keto-prostaglandin (PG)F_1a (a stable metabolite of prostacyclin) were measured using radioimmunoassay. The plasma level of CF6 was significantly increased in patients (254.1±29.8 pg/ml vs 219.4 ±36.7 pg/ml in controls, p<0.0001), whereas that of 6-keto-PGF_1a was significantly decreased (23.4 ±2.3 pg/ml vs 26.1±4.5 pg/ml in controls, p=0.001). Moreover, after percutaneous transluminal coronary angioplasty (PTCA) and stent therapy, the level of CF6 was further increased by 30% to 330.4±26.0 pg/ml, and that of 6-keto-PGF _1a was decreased by 42% to 13.5±2.0 pg/ml, compared with baseline (all p<0.01). Univariate analysis showed a significant result that the plasma level of CF6 was inversely correlated with that of 6-keto-PGF_1a in the patients. The plasma ratio of CF6 to 6-keto-PGF_1a was 8.4 in the control group and that in patients with coronary heart disease was increased to 24.4 after the therapy from 10.9 before therapy. Conclusions The results suggest that an increased CF6 level may be responsible in part for the decreased prostacyclin level observed in patients with coronary heart disease, in particular after PTCA and stent therapy. As a potential risk factor for coronary heart disease, CF6 might have important clinical significance. (Circ J 2007; 71: 693 - 697)