Efficacy and safety of subcutaneous semaglutide in adults with overweight or obese: a subgroup meta-analysis of randomized controlled trials.

Introduction: Semaglutide shows significant performance on weight reduction in several clinical trials. However, it is not clear what kind of administration frequency or dosage will achieve better effects. This study aims to explore the different therapeutic effect of semaglutide on weight control under the diverse administration circumstances. Methods: The PubMed, Embase, Web of Science, Cochrane Library, and the Clinical Trials.gov were searched from inception until 6 June, 2022 to include randomized controlled trials evaluating the Efficacy and safety of subcutaneous semaglutide in overweight or obese adults. Random effects or fixed effects model was conducted based on the heterogeneity among trials. Subgroup analysis was performed to identify the detailed effects under different intervention situations. Results and discussion: Our study included 13 RCTs involving 5,838 participants with 3,794 ones in semaglutide group and 2,044 in placebo group. Semaglutide was associated with a significant reduction on weight loss related outcomes, including the absolute value of weight loss (WMD -8·97, 95% CI -10·73 to -7·21), percentage of weight loss (WMD -10·00, 95% CI -11·99 to -8·00), body mass index (WMD-3·19, 95% CI -4·02 to -2·37) and waist circumference (WMD -7·21,95% CI -8·87 to -5·56). Subgroup analyses illustrated participants with high weekly dosage, long-term treatment duration and severe baseline BMI (Class II obesity) had a more remarkably decreasing on the main outcomes of weight loss (P for interaction<0·05). Total adverse reactions occurred more frequently in the daily administration group than that in the weekly group (P for interaction =0·01). During the treatment, the incidence rate of hypoglycemia was higher in the group without lifestyle intervention compared with that with lifestyle intervention (P for interaction =0·04). Interpretation Subcutaneous semaglutide had significant benefits on weight loss with reasonable safety in overweight or obese adults. Moreover, additional benefits on cardiometabolic profiles were also seen. We recommended semaglutide treatment to be coupled with lifestyle interventions, and target dose of 2·0 mg or more subcutaneously once weekly. Clinicians can choose suitable treatment schemes based on diverse individual situations. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=337099, identifier PROSPERO (CRD42022337099).

Rapamycin inhibits activation of AMPK-mTOR signaling pathway-induced Alzheimer's disease lesion in hippocampus of rats with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is strongly correlated with Alzheimer's disease (AD). Rapamycin has important uses in oncology, cardiology and transplantation medicine. This study aims to investigate effects of rapamycin on AD in hippocampus of T2DM rat by AMPK/mTOR signaling pathway. METHODS: Morris water maze test was applied to evaluate the learning and memory abilities. The fasting plasma glucose (FBG), glycosylated haemoglobin, total cholesterol, triglyceride and serum insulin level were measured. RT-qPCR and Western blot analysis were performed to test expression of AMPK and mTOR. Immunohistochemistry was used to detect the Aß deposition and immunoblotting to test the total tau, p-tau and Aß precursor APP expressions. RESULTS: After treated with rapamycin, T2DM rats and rats with T2DM and AD showed increased learning-memory ability, and decreased levels of FBG, glycosylated hemoglobin, total cholesterol, triglyceride and serum insulin, decreased expression of APP and p-tau, increased AMPK mRNA expression and p-AMPK and decreased Aß deposition, mTOR mRNA expression and p-mTOR. CONCLUSION: The study demonstrated that rapamycin reduces the risk of AD in T2DM rats and inhibits activation of AMPK-mTOR signaling pathway, thereby improving AD lesion in hippocampus of T2DM rats.

Synergistic effect of zinc and vitamin A on T cell functions.

OBJECTIVE: To determine whether supplementation of zinc and vitamin A may improve the function of T cells in human PBMC. METHODS: T cells were separated and cultured in vitro, supplemented with either Zn or vitamin A alone, or both Zn and vitamin A (10(-6) mol/L, 10(-5) mol/L, 10(-4) mol/L). After harvesting, cell proliferation, cell cycle, apoptosis, expression or function of cell-surface molecules, such as CD3+, CD4+, and CD8+ were detected. RESULTS: Higher proliferation level and lower apoptosis level were observed in cells supplemented with both Zn and vitamin A, showing the strongest effect (P < 0.05). Zn-supplement increased the CD4+/CD3+ cell percentage, and simultaneously decreased the CD8+/CD3+ cell population. VA-supplement showed the opposite effect in comparison with Zn-supplement. CONCLUSION: T-cell function can be improved, depending on the zinc and/or vitamin A supplemented.

[Combination effects of vitamin A and zinc on human's PMBC DNA damage in vitro].

OBJECTIVE: To study the combination effects of vitamin A (Vit. A) and zinc on human's PBMC DNA damage in vitro. Methods The PBMC from healthy volunteer was purification and cultured in the basic culture medium with Vit.A of 10(-4), 10(-5) and 10(-6) mol/L, or/and with Zn of 10(-6), 10(-5) 10(-4) and 10(-3) mol/L. The basic culture medium with K2Cr2O7 of 1 mmol/L was the male control. The damage of PBMC DNA was respectively examined by SCGE and the image analyzer measured the comet tail rate and length. The apoptosis of each group PBMC was detected by FCM. RESULTS: The overdose supplement of zinc and Vit. A can damage the PBMC DNA in vitro culture (P < 0.01), while the suitable supplement doesn't find. When the Vit. A supplement has been excessive, giving suitable zinc could repair the damage of DNA, but would expand the injured cell. While when the zinc supplement has been excessive, giving suitable Vit. A could protect the healthy cells, but would aggravate the damage degree of injured cell. CONCLUSION: In vitro culture, the overdose Vit. A and zinc supplement could damage the human's PBMC DNA significantly. This need more researches to provide.