Effects of continuous use of metformin on cardiovascular outcomes in patients with type 2 diabetes after acute myocardial infarction: A protocol for systematic review and meta-analysis

Background:To our knowledge, no meta-analyses or reviews have investigated the efficacy and safety of metformin on cardiovascular outcomes after acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus (T2DM). We thus conduct a high-quality systematic review and meta-analysis to assess the efficacy and safety of metformin on cardiovascular outcomes after AMI in patients with T2DM.Methods:In this systematic review and meta-analysis, we will search PUBMED, Scopus, EMBASE, and Cochrane Library databases through April, 2021. The study is structured to adhere to PRISMA guidelines (i.e., Preferred Reporting Items for Systematic Reviews and Meta-analyses). The literature search, data extraction, and quality assessments are conducted independently by 2 authors. Outcome measures include all-cause mortality; complications such as acute kidney injury, lactic acidosis, hospitalization for AMI or stroke, or death. Where disagreement in the collection of data occurs, this is resolved through discussion. Review Manager Software (v 5.3; Cochrane Collaboration) is used for the meta-analysis. Two independent reviewers will assess the risk of bias of the included studies at study level.Results:It is hypothesized that metformin use at the post-AMI is associated with decreased risk of cardiovascular disease and death in patients with T2DM.Conclusions:This study expects to provide credible and scientific evidence for the efficacy and safety of metformin on cardiovascular outcomes after AMI in patients with T2DM.Registration number:10.17605/OSF.IO/S3MBP.     

Acupuncture therapy and cognitive dysfunction in patients with type 2 diabetes: A protocol for systematic review

Background:With the aging of society, the incidence of type 2 diabetes (T2DM) is increasing every year, and there is a clear correlation between T2DM and cognitive dysfunction. Acupuncture therapy has been widely used in the treatment of T2DM, but there is no systematic review on the treatment of T2DM associated with cognitive impairment. Therefore, this study aimed to conduct a meta-analysis of acupuncture in the treatment of T2DM with cognitive impairment to clarify its efficacy.Methods:A structured and systematic literature search will be conducted in the following databases up to April 26, 2021: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (WOS), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Chinese Scientific and Journal Database (VIP), and Wan Fang database (Wanfang). We will use the Review Manager 5.4 software provided by the Cochrane Collaborative Network for statistical analysis. We then assessed the quality and risk of the included studies and observed the outcome measures.Results:This meta-analysis further determined the beneficial effects of acupuncture on T2DM with cognitive impairment.Conclusion:The purpose of this meta-analysis was to explore the effect of acupuncture on patients T2DM with and cognitive impairment patients, and provide more options for clinicians and patients to treat T2DM with cognitive impairment.Ethics and dissemination:This systematics review will evaluate the efficacy and safety of acupuncture in the treatment of T2DM with cognitive impairment. Since all the data included were published, the systematic review did not require ethical approval.Registration number:CRD42021245681.     

The efficacy and safety of glucokinase activators for the treatment of type-2 diabetes mellitus: A meta-analysis

Background:Glucokinase activators (GKAs) are a novel family of glucose-lowering agents used for the treatment of type-2 diabetes mellitus. Treatment with different GKAs has been shown to reduce blood glucose levels in these patients. We compared the efficacy/safety of GKAs in patients with type-2 diabetes mellitus through a meta-analysis.Methods:We searched the PubMed, Excerpt Medica Database, and Cochrane Central Register of Controlled Trials databases for articles published before December 30, 2020. We computed the weighted mean difference (WMD) and 95% confidence interval (CI) for the change from baseline to the study endpoint for GKA versus placebo treatments.Results:A total of 4 articles (5 studies) were included in the meta-analysis. GKAs were associated with reductions in glycated hemoglobin levels from baseline (WMD, −0.3%; 95% CI, −0.466% to −0.134%). No significant difference between GKA and placebo treatment was observed in the results of fasting plasma glucose levels from baseline (WMD 0.013 mmol/L; 95% CI, −0.304–0.33 mmol/L). A significantly higher change in 2-hour postprandial plasma glucose (2-h PPG) levels (WMD −2.434 mmol/L; 95% CI, −3.304 to −1.564 mmol/L) was observed following GKA than placebo treatment. GKAs were associated with a higher prevalence of causing hypoglycemic events than placebo treatment (risk difference [RD], 0.06; 95% CI 0.013–0.106). GKAs had no association with the risk of developing adverse effects (RD, 0.038; 95% CI, −0.03–0.106) and serious adverse events (RD, 0.01; 95% CI, −0.004–0.023).Conclusions:GKAs were more effective for postprandial blood glucose control. However, these agents showed a significantly high risk of causing hypoglycemia.PROSPERO registration number:CRD42021220364.     

Acupuncture for type 2 diabetes mellitus with nonalcoholic fatty liver disease: A protocol for systematic review and meta-analysis

Background:T2DM with NAFLD is a common disorder of glucose and lipid metabolism affecting the quality of life of patients. Due to the limitations and adverse reactions of drug treatment, acupuncture has been proved to be an effective method for the treatment of T2DM with NAFLD. This study aims to evaluate the efficacy and safety of acupuncture in the treatment of NAFLD in T2DM class, and to provide high-quality evidence for acupuncture in the treatment of this disease.Methods:From establishment of the database to 31 July 2021, We will search the Cochrane Central Register of controlled trials, PubMed, MEDLINE, EMBASE, Web of science. Five Chinese databases, including China National Knowledge Infrastructure (CNKI), WanFang database, VIP, Chinese Biomedical Literature Database (CBM) and the Chinese clinical trial registry. There are no restrictions on language or publication, and they are independently screened and collected by two reviewers. Review Manager 5.3 software will be used for meta analysis. If necessary, heterogeneity testing, data synthesis, and subgroup analysis will be performed.Results:The effectiveness and safety of acupuncture in the treatment of T2DM with NAFLD will be assessed by the outcomes of test''s, including: imaging indicators, biomarkers of hepatic steatosis, serological indicators of hepatic fibrosis, improvement of serum NAFLD liver fat score, BMI, blood glucose indexes, blood lipid indexes, insulin level and safety indicators.Conclusion:This meta-analysis will further determine the beneficial efficacy and safety of acupuncture for T2DM combined with NAFLD.     

The efficacy of sodium glucose co-transport-2 inhibitors on glycemic control for patients with type 1 diabetes mellitus: A protocol for systematic review and meta-analysis

Background:Currently, there are a number of sodium glucose co-transport-2 (SGLT2) inhibitors that are under development or in clinical trials. Prior meta-analyses had established the safety and efficacy of SGLT2 inhibitors in type 1 diabetes mellitus (T1DM), but with low level of evidences and inconsistent conclusions. However, recently many new randomized clinical trials (RCTs) have been published, we hence try to design a study protocol to assess the effect of SGLT2 inhibitors on cardiovascular events via a comprehensive meta-analysis of data from much more RCTs, including sensitivity and subgroup analyses.Methods:We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines to conduct this meta-analysis. Two investigators will perform a systematic search of scientific literature in the databases (from conception through June 12, 2021), including PubMed, Embase, and Cochrane Central Register of Controlled Trials. This meta-analysis will be conducted using RevMan statistical software. The risk of bias for each included study will be assessed using the Cochrane Risk of Bias Assessment Tool.Results:Our protocol is conceived to test the hypothesis that SGLT2 inhibitors could lead to better outcomes in patients presenting with T1DM.Registration number:10.17605/OSF.IO/ZD8WX.     

Pancreatic safety of DPP-4 inhibitors in type 2 diabetes millitus: A protocol for systematic review and network meta-analysis

Background:Dipeptidyl-peptidase IV inhibitor (DPP-4i) is a common hypoglycemic medication in treating type 2 diabetes millitus. It has become widely utilized in clinical practice due to its ability to effectively manage blood glucose while posing a low risk of hypoglycemia and weight gain. However, there is no consensus on DPP-4i''s pancreatic safety due to a paucity of clinical evidence. The safe event appears to be easily overlooked. This review aims to evaluate the pancreatic safety of DPP-4i in patients with type 2 diabetes mellitus using the standard pairwise and network meta-analysis methods.Methods:MEDLINE, Embase, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials will be used to search for published literature on the pancreatic safety of DPP-4 inhibitors in type 2 diabetes millitus, and clinical trial registries will be used to look for unpublished trials. Two independent reviewers will screen literature for eligibility, extract available data, and assess the risk of bias. All divergences will be resolved after rechecking the source papers and further discussion among the reviewers with a complete consensus before inclusion. The risk of bias will be assessed by the Cochrane bias risk tool, and the quality of evidence will be interpreted by the GRADE Working Group approach. We will use STATA16.0 and WinBUGS1.4.3 for paired meta-analysis and Bayesian network meta-analysis.Results:This study will evaluate the pancreatic safety of DPP-4 inhibitors in type 2 diabetes millitus.Conclusion:This systematic review and network meta-analysis will evaluate the pancreatic safety of DPP-4i in patients with type 2 diabetes millitus. The findings of this study may supplement the evidence-based information on DPP-4i, improve existing understanding of this issue, and assist patients and clinicians in making better treatment decisions by raising their awareness of the problem.Protocol registration number:INPLASY202230014.     

Efficacy and safety of novel dual glucokinase activator dorzagliatin in type-2 diabetes A meta-analysis

Background & aimsGlucokinase has a critical role in regulating glucose homeostasis in humans, and has been a target for diabetes drug development since 1990s. Dorzagliatin is a novel allosteric dual glucokinase activator targeting both pancreatic and hepatic glucokinase. No meta-analysis has analysed the efficacy and safety of dorzagliatin in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge-gap.MethodsElectronic databases were searched for RCTs involving T2DM patients receiving dorzagliatin in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in blood glucose parameters, lipids, insulin-resistance and adverse events.ResultsFrom initially screened 17 articles, data from 3 RCTs (1333 patients) was analysed. Over 12–24 weeks use, dorzagliatin had significantly higher lowering of HbA1c [MD -0.66% (95%CI: ?0.74 to ?0.59); P < 0.01; I² = 99%], fasting glucose [MD -32.03 mg/dl (95%CI: 45.12 to ?18.94); P < 0.01; I² = 100%], 2-h post-prandial glucose [MD -43.49 mg/dl (95%CI: ?46.26 to ?40.72); P < 0.01; I² = 90%] along with greater number of patients achieving HbA1c<7% [OR 6.01 (95% CI: 2.50–14.46); P < 0.01; I² = 83%], as compared to placebo. Dorzagliatin was associated with significant elevation of triglycerides [MD 0.43 mmol/L (95%CI:0.30–0.56); P < 0.01; I² = 0%], greater occurrence of hyperlipidaemia [RR 1.52 (95% CI:1.05–2.18); P = 0.03; I² = 0%], and increase in body-weight [MD 0.40 kg (95%CI:0.06–0.75); P = 0.03; I² = 0%], compared to placebo. The occurrence of total-adverse-events [RR 1.43 (95%CI:1.11–1.83); P < 0.01; I² = 0%] but not severe adverse-events [RR 0.92 (95%CI:0.54–1.57); P = 0.76; I² = 0%] was significantly higher with dorzagliatin.ConclusionDorzagliatin has good glycaemic efficacy and well tolerated over 6-months use. Mild increase in body-weight, serum triglycerides and overall adverse events remain issues of concern warranting further evaluation in longer clinical trials with active controls.     

Efficacy and safety of pasireotide for Cushing's disease: A protocol for systematic review and meta-analysis

Background:Cushing''s disease (CD) is associated with increased risk of mortality, myocardial infarction, stroke, peptic ulcers, fractures and infections. The prevalence of CD is nearly 40 per million and higher in women than in men. When surgery has failed, is not feasible, or has been refused, pharmacotherapy can be considered a valuable option. Pasireotide is the first medical therapy officially approved for adult patients with CD. We will conduct a comprehensive systematic review and meta-analysis to systematically evaluate the efficacy and safety of pasireotide for CD.Methods:Five English databases (PubMed, Web of Science, Embase, Cochrane Library, and OVID) and 3 Chinese databases (China National Knowledge Infrastructure, China Science and Technology Journal Database, and Chinese Biomedical Literature Database) will be searched from their respective inception of databases to December 2020. Two reviewers will select articles, extract data and assess the risk of bias independently. Any disagreement will be resolved by discussion with the third reviewer. Review Manager 5.3 software will be used for data synthesis. The Cochrane risk of bias assessment tool will be used to evaluate the bias risk.Results:This systematic review and meta-analysis will conduct a comprehensive literature search and provide a systematic synthesis of current published data to explore the efficacy and safety of pasireotide for CD.Conclusions:This systematic review and meta-analysis will provide clinical evidence for the efficacy and safety of pasireotide for CD, and inform our understanding of the value of pasireotide in improving CD clinical signs and symptoms. The conclusions drawn from this study may be beneficial to patients, clinicians, and health-related policy makers.Study registration number:INPLASY2020110070.     

The efficacy and safety of moxibustion for pressure injury: A protocol for systematic review and meta-analysis

Background:Pressure injury is an important global health issue characterized by the high incidence, rapid progression, and difficult healing. How to perform timely treatment and care have been the current focus and challenge for health care professionals. Moxibustion can improve skin microcirculation, promote blood circulation, activate tissue cells, inhibit, and kill bacteria on the wounded surface, thus promoting wound healing. However, the clinically reported efficacy of moxibustion in the treatment of pressure injuries varies a lot and lacks evidence-based medical evidence. Therefore, this meta-analysis aims to evaluate the efficacy and safety of moxibustion on the treatment of pressure injuries.Methods:Randomized controlled trials (RCTs) reporting the moxibustion for pressure injury published before January 2022 will be searched in online databases, including the Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, Wanfang Database, China Biomedical Literature Database, PubMed, Cochrane Library, Embase, and Web of Science. References of eligible literatures will be manually reviewed. According to inclusion and exclusion criteria, literature screening, data extraction and quality assessment will be independently performed by 2 reviewers, and meta-analysis of relevant data will be conducted using Stata14.0 software.Results:The study will provide a high-quality convincing assessment of efficacy and safety of moxibustion for pressure injury.Conclusion:The results of this study will provide the latest evidence support for judging the efficacy and safety of moxibustion on the treatment of pressure injury.OSF Registration number:DOI 10.17605/OSF.IO/T543Y.     

Semaglutide for the treatment of type 2 Diabetes Mellitus: A systematic review and network meta-analysis of safety and efficacy outcomes

Background and aimsTo assess the safety and efficacy of semaglutide compared with placebo and other anti-hyperglycaemic agents in type 2 diabetes (T2DM).MethodsWe searched PubMed, Scopus, Web of Science, and Cochrane library for relevant randomized controlled trials (RCTs). A network meta-analysis was conducted to compare different doses, durations, and interventions in T2DM. We presented results as mean difference (MD) or relative risk (RR) and 95% confidence interval (CI).ResultsTwenty-six included RCTs studied different doses of subcutaneous (SC) and oral semaglutide, tirzepatide, liraglutide, sitagliptin, canagliflozin, and empagliflozin compared with placebo. Tirzepatide showed the highest efficacy, however, it was comparable to semaglutide. SC semaglutide 1 mg once-weekly showed higher reduction in HbA_1c (MD = ?1.72, 95% CI [-2.32; ?1.12]), and fasting blood glucose (MD = ?1.93, 95% CI [-2.81; ?1.04]) versus placebo at 30 weeks and other timepoints. Adverse events (ADs) were comparable to placebo with oral and SC semaglutide, oral sitagliptin, SC liraglutide, and oral empagliflozin at most timepoints. However, SC semaglutide 0.8 mg and tirzepatide 10 mg groups had the highest gastrointestinal adverse events.ConclusionTirzepatide, oral and SC semaglutide has a favourable efficacy in treating T2DM. The adverse events were comparable to placebo; however, gastrointestinal adverse events were highly recorded in tirzepatide, oral and SC semaglutide groups.     

Which of the acupuncture treatment regimen for lumbar disc herniation is more effective and safer: A protocol for systematic review and network meta-analysis

Introduction:Lumbar disc herniation (LDH) is the most common cause of low back pain and severely affects people''s quality of life and ability to work. Although many clinical trials and medical reports conducted over the years have shown that acupuncture treatments are effective for LDH, the comparative effectiveness of these different acupuncture therapies is still unclear. This protocol of a network meta-analysis was designed to compare the effects and safety of acupuncture treatment regimens on LDH using both direct and indirect evidence.Methods and analysis:This protocol is reported according to the 2015 PRISMA-P and PRISMA guidelines for acupuncture. Eight databases and two platforms will be searched for articles published from their establishment to 1 December 2020 with medical subject heading terms and keywords. Three reviewers will verify the eligible randomized controlled trials independently. NoteExpress (3.2.0) software will be utilized to manage the literature. The overall quality of evidence will be evaluated by Confidence In Network Meta-Analysis (CINeMA). Additionally, we will conduct a meta-analysis of the effectiveness, recurrence rate, and symptom score of acupuncture in treating LDH using Review Manager (RevManV.5.4.1) and R4.0.2 software (The R Foundation for Statistical Computing).Results:The results of the study will be published in journals or relevant conferences.Conclusion:This proposed systematic review will evaluate the comparative efficacy and safety of various acupuncture methods and combination protocols for LDH.     

Evaluation of efficacy and safety of propofol in the treatment of procedural sedation/anesthesia in neonates: A protocol for systematic review and meta-analysis

Background:In newborns, propofol anesthesia is commonly utilized. Propofol is increasingly being shown to be effective and safe in treating procedural sedation and anesthesia in neonates. This research aims to evaluate the efficacy and safety of propofol in neonates using systematic review and meta-analysis methodologies.Methods:A thorough review and meta-analysis of studies on propofol anesthesia in neonates will be conducted. Conduct comprehensive searches in Web of Science, PubMed, Cochrane Library, EMBASE database, WanFang database, and Chinese biomedical literature database before May 25, 2021, to obtain published and qualified research. Two reviewers will assess the quality of the included papers and extract the data independently. Then, for meta-analysis, we will utilize RevMan 5.3 software.Results:This study will pool the data of separate trials to analyze the efficacy and safety of propofol in the treatment of procedural sedation/anesthesia in neonates.Conclusion:Our findings will give strong data for determining whether propofol is an effective treatment for procedural anesthesia in neonates.     

Efficacy and safety of colchicine in the treatment of acute myocardial infarction: A protocol for systematic review and meta-analysis

Background:There are no meta-analyses evaluating the efficacy and safety of colchicine in the treatment of acute myocardial infarction (AMI). Our protocol is conceived to evaluate the efficacy and safety of colchicine in comparison of placebo and test the hypothesis that a short course of treatment with colchicine could lead to reduced infarct size in patients presenting with AMI.Methods:We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines and the recommendations of the Cochrane Collaboration to conduct this meta-analysis. Reviewers will search the PubMed, Cochrane Library, Web of Science, and EMBASE online databases for all English-language cohort studies published up to April, 2021. The cohort studies focusing on assess the efficacy and safety of colchicine in the treatment of AMI will be included in our meta-analysis. At least one of the following outcomes should have been measured: reduced infarct size, C-reactive protein (CRP) level, adverse events, death and major cardiovascular events. Review Manager software will be used for the meta-analysis. All outcomes are pooled on random-effect model. A P value of <.05 is considered to be statistically significant.Results:Our protocol is conceived to evaluate the efficacy and safety of colchicine in comparison of placebo and test the hypothesis that a short course of treatment with colchicine could lead to reduced infarct size in patients presenting with AMI.Registration number:10.17605/OSF.IO/NTU5F.     

Association of vitamin D receptor gene polymorphism with type 1 diabetes mellitus risk in children: A protocol for systematic review and meta-analysis

Background:Recent genetic association studies showed that there are contradictory results on the relationship between vitamin D receptor (VDR) gene polymorphisms and type 1 diabetes mellitus (T1DM) risk in children. The purpose of this systematic review is to collect the currently available evidence to evaluate the relationship between VDR gene polymorphisms and the risk of T1DM in children.Methods:Such medical databases as Wanfang Data, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science were extensively searched for relevant literatures published before June 2021 with the focus on the relationship between VDR gene polymorphisms and the risk of T1DM in children. The risk of bias was evaluated as per the Newcastle-Ottawa Scale by 2 independent researchers. Meta-analysis was performed to quantify the relationship between VDR gene polymorphisms and T1DM risk in children.Results:The results of this meta-analysis would be submitted to a peer-reviewed journal for publication.Conclusion:The relationship between VDR gene polymorphisms and T1DM risk in children is explored via this meta-analysis.Ethics and dissemination:Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms.Osf Registration Number:DOI 10.17605/OSF.IO/Q8XA5.     

Efficacy and safety of acupuncture combined with Chinese herbal medicine in the treatment of type 2 diabetes mellitus: A protocol for a systematic review and meta-analysis

Background:Diabetes has become a global public health problem and danger to human health. Diabetes is the main cause of blindness, kidney failure, heart attack, stroke, and lower limb amputation. According to the latest epidemiological survey and research, the overall prevalence of diabetes in mainland China is 11.2%, of which type 2 diabetes mellitus (T2DM) accounts for more than 90% acupuncture combined with Chinese herbal medicine have been widely used in the treatment of T2DM. However, we have not found a meta-analysis of their synergistic effects. Therefore, this systematic review and meta-analysis aims to evaluate the efficacy and safety of acupuncture combined with Chinese herbal medicine in the treatment of T2DM.Method:From inception up to September 20, 2021, the PubMed, Web of Science, Embase, AMED, Cochrane Library, CNKI, VIP, CBM, and Wanfang databases will be searched. The publication date or language will not be limited. We will apply a combination of medical keywords, including “acupuncture”, “Chinese herbal medicine”, and “type 2 diabetes mellitus”. We will also check other ongoing and unpublished studies in the clinical trial registry. At the same time, we will manually search all reference lists from relevant systematic reviews to find other eligible studies. We will use Review Manager software (REVMAN v5.3 Cochrane Collaboration) to meta-analyze the selected literature. The study for acupuncture combined with Chinese herbal medicine in the treatment of T2DM was a randomized controlled study. Two researchers will independently review the research selection, data extraction, and research quality assessments. Finally, we will observe the outcome measures.Results:This study will generate evidence-based data on the treatment of T2DM with acupuncture combined with Chinese herbal medicine and will provide new ideas and treatment modalities to investigate in future research.     

Efficacy and safety evaluation of acupuncture in the treatment of impaired glucose regulation: A protocol for systematic review and meta-analysis

Background:Impaired of glucose regulation belongs to the stage of prediabetes, which is a state of glucose metabolism between diabetes and normal blood glucose. The prevalence of prediabetes in people over 20 years old in China is significantly higher than that in diabetic patients. If no measures are taken to prevent the transition from prediabetes to diabetes, the number of diabetic patients in China will further increase. This study conducted a meta-analysis of the effectiveness of acupuncture in the treatment of impaired glucose regulation by collecting relevant literatures.Methods:Nine electronic databases: PubMed, EMBASE, Cochrane library, Web of Science, Google Scholar, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific and Journal Database, Wan Fang database, and 2 clinical trials register platforms: Chinese Clinical Trial Registry, ClinicalTrials.gov (www.ClinicalTrials.gov/) will be searched for randomized clinical trails of acupuncture for impaired glucose regulation. The screening process will be developed by 2 independent reviewers, and meta-analysis will be performed with RevMan (V5.3.5) software.Results:This meta-analysis further confirmed the benefits of acupuncture in the treatment of impaired of glucose regulation.Conclusion:This study will provide a high-quality evidence of the efficacy and safety of acupuncture on patients with impaired glucose regulation.PROSPERO registration number:INPLASY202170058.Ethics and dissemination:This systematics review will evaluate the efficacy and safety of acupuncture in the treatment of impaired of glucose regulation. Since all the data included were published, the systematic review did not require ethical approval.     

Glucokinase activation or inactivation: Which will lead to the treatment of type 2 diabetes?

Glucokinase, which phosphorylates glucose to form glucose-6-phosphate, plays a critical role in regulating blood glucose levels. On the basis of data of glucokinase-knockout and transgenic mice and humans with glucokinase mutations, glucokinase was targeted for drug development aiming to augment its activity, and thereby reduce hyperglycaemia in patients with diabetes. In fact, various small molecule compounds have been developed and clinically tested as glucokinase activators. However, some have been discontinued because of efficacy and safety issues. One of these issues is loss of the drug's efficacy over time. This unsustained glycaemic efficacy may be associated with the excess glycolysis by glucokinase activation in pancreatic beta cells, resulting in beta-cell failure. Recently, we have shown that glucokinase haploinsufficiency ameliorated glucose intolerance by increasing beta-cell function and mass in a mouse model of diabetes. Given that a similar phenotype has been observed in glucokinase-activated beta cells and diabetic beta cells, glucokinase inactivation may be a new therapeutic target for type 2 diabetes.     

Efficacy and safety of Huangkui capsule for diabetic nephropathy: A protocol for systematic review and meta-analysis

Background:Diabetic nephropathy (DN) is 1 of the most serious complications of diabetes mellitus and the leading cause of end-stage renal disease in the world. Huangkui capsule, extracted from Abelmoschus manihot (L.) medic (AM), has been widely used to treat DN. However, there is no consensus on the efficacy of Huangkui capsule for DN. This study aims to perform meta-analysis to systematically review the efficacy and safety of Huangkui capsule.Methods:The following 9 electronic databases will be comprehensively searched: PubMed, web of science, MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang data, and Chinese BioMedicine Literature Database. The retrieval time is from their inception to May 2021. According to the inclusion and exclusion criteria, 2 reviewers independently completed the study selection, data extraction, risk of bias assessment, and data synthesis. Review Manager Version 5.3 software will be used to conduct meta-analysis.Results:This study provides a high-quality synthesis to assess the efficacy of Huangkui capsule for treating diabetic nephropathy.Conclusion:The result of this systematic review will provide objective evidence-based basis to judge the effectiveness and safety of Huangkui capsule on diabetic nephropathy.     

Dipeptidyl peptidase-4 inhibitors and protection against stroke: A systematic review and meta-analysis

BackgroundType 2 diabetes mellitus (T2DM) is associated with an increased risk of stroke and an unfavourable outcome following stroke. Apart from pioglitazone, glucose-lowering modalities have not been shown to protect against stroke. Nevertheless, there is evidence from experimental studies of potential neuroprotective effects with dipeptidyl peptidase (DPP)-4 inhibitors, especially if treatment starts before stroke.ObjectiveTo perform a meta-analysis of available evidence regarding the risk of stroke in individuals taking DPP-4 inhibitors.MethodsAll available data from prospective randomized placebo-controlled trials involving DPP-4 inhibitors in T2DM patients published up to December 2015 were considered. The included trials reported data on the incidence of stroke with a recruitment rate of at least 100 diabetes patients and a follow-up of at least 12 weeks.ResultsA total of 19 small randomized clinical trials (RCTs) evaluating the efficacy and safety of gliptins (n = 9278), along with three multicentre prospective double-blind placebo-controlled RCTs assessing cardiovascular outcomes as the primary endpoint and involving 36,395 T2DM patients, were included in the analysis. Pooled analysis of the small RCTs showed a non-significant trend towards benefit with DPP-4 inhibitors against stroke [odds ratio (OR): 0.639, 95% confidence interval (CI): 0.336–1.212; P = 0.170]. In contrast, in the analysis of RCTs reporting on cardiovascular safety, there was no difference in the risk of stroke with gliptin treatment compared with a placebo (OR: 0.996, 95% CI: 0.850–1.166; P = 0.958).ConclusionThe promising data from experimental studies regarding cardioprotective gliptin-associated effects against stroke were not supported by available data from trials specifically looking at cardiovascular safety.     

The efficacy and safety of traditional Chinese medicine's tonifying-kidney,strengthening-spleen,and invigorating-blood circulation (Bushen-Jianpi-Huoxue) principle for type 2 diabetes mellitus with osteoporosis: A protocol for systematic review and meta-analysis

Background:Type 2 diabetes mellitus (T2D) and osteoporosis (OP) often coexist, and both are systemic metabolic diseases and seriously increase the risk of fragility fracture. However, there is no specific Western medicine for the treatment of T2D with OP (T2DOP). As reported in clinical and experimental studies, traditional Chinese medicine (TCM) based on principle of tonifying-kidney, strengthening-spleen, and invigorating blood circulation (Bushen-Jianpi-Huoxue) (BSJPHX) has significant efficacy against T2DOP. This protocol will be designed for a systematic review and meta-analysis to assess the efficacy and safety of TCM BSJPHX principle in the treatment of T2DOP.Methods:All relevant randomized controlled trials (RCTs) related to TCM therapies conducted in BSJPHX principle for T2DOP will be searched in the 8 electronic databases: PubMed, Cochrane Library, Wed of Science, EMBASE, Chinese National Knowledge Infrastructure Database (CNKI), Chinese Biomedical Literatures Database (CBM), Chinese Scientific Journal Database (VIP), Wanfang Database, from inception to October 2020. The main outcomes will contain: fasting blood glucose (FPG), 2 hours postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA1c), serum calcium, bone mineral density (BMD), TCM syndrome integral, and the additional outcomes will consist of visual analog scale (VAS), and adverse events. Two reviewers will independently carry out literature search, data selection and synthesis, and literature quality assessment. In case of any dispute, it will be settled by group discussion. Assessment of risk of bias, reporting bias, and data synthesis would be performed with Review Manager software (Rev-Man 5.3).Result:This study will collate and summarize the various current evidences of TCM BSJPHX principle for T2DOP.Conclusion:This study will offer convincing evidence for judging the efficacy and safety of TCM BSJPHX principle for T2DOP.PROSPERO registration number:CRD42020218877.