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Medicine May 2017We aimed to assess the safety and efficiency of the novel sodium glucose co-transporter 2 (SGLT2) inhibitor in combinations with insulin for type 1 and type 2 diabetes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We aimed to assess the safety and efficiency of the novel sodium glucose co-transporter 2 (SGLT2) inhibitor in combinations with insulin for type 1 and type 2 diabetes mellitus (T1DM and T2DM).
METHODS
We searched Medline, Pubmed, Embase, and the Cochrane Collaboration Library from January 2010 to December 2016 without restriction of language. FDA data and Clinical Trials (http://www.clinicaltrials.gov) were also searched. Study selection, data extraction, and evaluation of risk of bias were performed by 2 persons independently. The risk of bias was assessed by Cochrance System Evaluate Method and Q test was used to evaluate the heterogeneity between studies. We used random effect model to analyze the results by Revman 5.3. This meta-analysis has been registered at online public registry PROSPERO (registration number is: CRD42017054718).
RESULTS
Nine trials including 3069 patients were analyzed. Compared with control group, SGLT2 inhibitor produced absolute reduction in glycosylated hemoglobin A1c (HbA1c) (MD -1.35%, 95% confidence interval [CI] [-2.36 to -0.34], P = .009), fasting plasma glucose (FPG) (MD -1.01 mmol/L, 95%CI [-1.98 to 0.04], P = .04), insulin dosage (MD -4.85 U/24 hours, 95%CI [-7.42 to -2.29], P = .002), and body weight (MD -2.30 kg, 95%CI [-3.09 to -1.50], P < .00001). But the risk of hypoglycemia (OR 1.18, 95%CI [0.86, 1.61], P = . 30) and urinary tract infection (UTI) (OR 1.34, 95%CI [0.79, 2.27], P = .28) were proved as no difference and genital tract infection (GTI) with SGLT2 inhibitors was higher than control group (OR 2.96, 95%CI [1.05, 8.37], P = .04), in which cases were mild and responded to the therapy. According to the subgroup analysis, SGLT2 inhibitors had a similar effect in effective factors of both T1DM and T2DM, but the risk of GTI mainly increased in T2DM versus T1DM (T1DM OR 0.27 [0.01, 7.19], P = .43 vs T2DM OR 4.28 [2.00, 9.16], P = .0002).
CONCLUSION
SGLT2 inhibitors have improved the HbA1c, FPG, and body weight when combined with insulin and decreased the dose of insulin without increasing the risk of hypoglycemia. However, SGLT2 inhibitor was proved to be related to the events of GTI, despite SGLT2 inhibitors appeared to be well tolerated. We suggest that more monitoring should be done to prevent the events of GTI, and more randomized controlled trials should be planned next step.
Topics: Diabetes Mellitus; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 28538386
DOI: 10.1097/MD.0000000000006944 -
Movement Disorders : Official Journal... May 2021This comprehensive MDSGene review is devoted to 7 genes - TOR1A, THAP1, GNAL, ANO3, PRKRA, KMT2B, and HPCA - mutations in which may cause isolated dystonia. It followed... (Review)
Review
This comprehensive MDSGene review is devoted to 7 genes - TOR1A, THAP1, GNAL, ANO3, PRKRA, KMT2B, and HPCA - mutations in which may cause isolated dystonia. It followed MDSGene's standardized data extraction protocol and screened a total of ~1200 citations. Phenotypic and genotypic data on ~1200 patients with 254 different mutations were curated and analyzed. There were differences regarding age at onset, site of onset, and distribution of symptoms across mutation carriers in all 7 genes. Although carriers of TOR1A, THAP1, PRKRA, KMT2B, or HPCA mutations mostly showed childhood and adolescent onset, patients with GNAL and ANO3 mutations often developed first symptoms in adulthood. GNAL and KMT2B mutation carriers frequently have 1 predominant site of onset, that is, the neck (GNAL) or the lower limbs (KMT2B), whereas site of onset in DYT-TOR1A, DYT-THAP1, DYT-ANO3, DYT-PRKRA, and DYT-HPCA was broader. However, in most DYT-THAP1 and DYT-ANO3 patients, dystonia first manifested in the upper half of the body (upper limb, neck, and craniofacial/laryngeal), whereas onset in DYT-TOR1A, DYT-PRKRA and DYT-HPCA was frequently observed in an extremity, including both upper and lower ones. For ANO3, a segmental/multifocal distribution was typical, whereas TOR1A, PRKRA, KMT2B, and HPCA mutation carriers commonly developed generalized dystonia. THAP1 mutation carriers presented with focal, segmental/multifocal, or generalized dystonia in almost equal proportions. GNAL mutation carriers rarely showed generalization. This review provides a comprehensive overview of the current knowledge of hereditary isolated dystonia. The data are also available in an online database (http://www.mdsgene.org), which additionally offers descriptive summary statistics. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Adolescent; Adult; Anoctamins; Apoptosis Regulatory Proteins; Child; DNA-Binding Proteins; Dystonia; Dystonic Disorders; Genotype; Humans; Molecular Chaperones; Mutation; Phenotype
PubMed: 33502045
DOI: 10.1002/mds.28485 -
Annals of Medicine and Surgery (2012) May 2022We aim to evaluate the impacts of sodium-glucose co-transporter 2 inhibitors (SGLT-2), glucagon-like peptide 1 agonist (GLP-1RAs), and dipeptidyl peptidase-four (DPP4)... (Review)
Review
AIM
We aim to evaluate the impacts of sodium-glucose co-transporter 2 inhibitors (SGLT-2), glucagon-like peptide 1 agonist (GLP-1RAs), and dipeptidyl peptidase-four (DPP4) inhibitors on the levels of high-density lipoprotein, low-density lipoprotein, triglyceride and total cholesterol.
METHODS
The MEDLINE database was searched from inception till October 2021, for randomized controlled trials assessing the effects of sodium-glucose co-transporter two inhibitors (SGLT-2), glucagon-like peptide 1 agonist (GLP-1RAs), and dipeptidyl peptidase-four (DPP4) inhibitors on lipid levels.
RESULTS
A total of 57 trials were included in the analysis. Our pooled analysis demonstrates that SGLT-2 inhibitors significantly increase the levels of HDL (WMD = 0.07 mg/dL [0.06 to 0.08], P < 0.00001). SGLT-2 inhibitors were also found to be significantly associated with an increase in the levels of LDL (WMD = 0.11 mg/dL, [0.09-0.13 mg/dL, P < 0.00001). Pooled analysis also demonstrates that SGLT-2 inhibitors significantly reduce the levels of triglyceride (WMD = -0.10 mg/dL, [-0.13 to -0.06], P < 0.00001). Our pooled analysis demonstrates that SGLT-2 inhibitors significantly increased the levels of total cholesterol (WMD = 0.10 mg/dL, [0.06 to 0.15], P < 0.0001), whereas, GLP-1RAs significantly reduced the levels of total cholestrol (WMD = -0.18 mg/dL, [-0.34 to -0.02], P = 0.03).
CONCLUSION
This is the first head-to-head study comparing the effects of 3-novel glucose-lowering agents to lipid parameters. However, more trials are crucial to better understand the impact of glucose-lowering drugs on lipid parameters.
PubMed: 35637990
DOI: 10.1016/j.amsu.2022.103633 -
Diabetes Research and Clinical Practice Feb 2021We aimed to conduct a systematic review and meta-analysis regarding the use of incretin-based therapies including dipeptidyl peptidase-4 (DPP-4) inhibitors and... (Meta-Analysis)
Meta-Analysis
AIMS
We aimed to conduct a systematic review and meta-analysis regarding the use of incretin-based therapies including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists as well as sodium-glucose co-transporter-2 (SGLT2) inhibitorsin persons with posttransplantation diabetes mellitus (PTDM) so as to assess both their efficacy and safety.
METHODS
We searched for publications on Kidney/Renal Transplantation and DPP-4 inhibitors, GLP-1-receptor agonists and SGLT-2 inhibitors and included every study using these antidiabetics. A p-value < 0.05 was considered statistical significant.
RESULTS
Sixteen studies and 310 individuals with a mean age of 55.98 ± 8.81 years were included in the analysis. Participants received DPP-4 inhibitors in 8 studies, SGLT-2 inhibitors in 6 studies and GLP-1 receptor agonists in 2 studies, with a mean follow-up of 22.03 ± 14.95 weeks. Hemoglobin A1c (HbA1c) reduction was demonstrated in 10 studies (mean +/- standard deviation (MD) = - 0.38%, I = 45%). MD of HbA1c was -0.3741 and -0.4596 mg/dl for DPP-4 inhibitors and SGLT-2 inhibitors respectively. Nine studies demonstrated differences in fasting plasma glucose (FPG) (MD = - 25,76) and 5 studies in post-prandial glucose (PPG) (MD = - 6.61) before and following treatment. Most studies did not show adverse effects on the glomerular filtration rate (GFR) and hepatic function.
CONCLUSIONS
DPP-4 inhibitors and SGLT2 inhibitors appear both efficacious and safe in renal transplant recipients. More high-quality studies are required to guide therapeutic choices for PTDM.
Topics: Diabetes Mellitus, Type 2; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Incretins; Kidney Function Tests; Kidney Transplantation; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33338553
DOI: 10.1016/j.diabres.2020.108604 -
Frontiers in Endocrinology 2023Diabetic retinopathy (DR) is the most frequent complication of type 2 diabetes and remains the leading cause of preventable blindness. Current clinical decisions... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic retinopathy (DR) is the most frequent complication of type 2 diabetes and remains the leading cause of preventable blindness. Current clinical decisions regarding the administration of antidiabetic drugs do not sufficiently incorporate the risk of DR due to the inconclusive evidence from preceding meta-analyses. This umbrella review aimed to systematically evaluate the effects of antidiabetic drugs on DR in people with type 2 diabetes.
METHODS
A systematic literature search was undertaken in Medline, Embase, and the Cochrane Library (from inception till 17th May 2022) without language restrictions to identify systematic reviews and meta-analyses of randomized controlled trials or longitudinal studies that examined the association between antidiabetic drugs and DR in people with type 2 diabetes. Two authors independently extracted data and assessed the quality of included studies using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist, and evidence assessment was performed using the GRADE (Grading of recommendations, Assessment, Development and Evaluation). Random-effects models were applied to calculate relative risk (RR) or odds ratios (OR) with 95% confidence intervals (CI). This study was registered with PROSPERO (CRD42022332052).
RESULTS
With trial evidence from 11 systematic reviews and meta-analyses, we found that the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or dipeptidyl peptidase-4 inhibitors (DPP-4i) was not statistically associated with the risk of DR, compared to either placebo (RR: GLP-1 RA, 0.98, 0.89-1.08; SGLT-2i, 1.00, 95% CI 0.79-1.27; DPP-4i, 1.17, 0.99-1.39) or other antidiabetic drugs. Compared to other antidiabetic drugs, meglitinides (0.34, 0.01-8.25), SGLT-2i (0.73, 0.10-5.16), thiazolidinediones (0.92, 0.67-1.26), metformin (1.15, 0.81-1.63), sulphonylureas (1.24, 0.93-1.65), and acarbose (4.21, 0.44-40.43) were not statistically associated with the risk of DR. With evidence from longitudinal studies only, insulin was found to have a higher risk of DR than other antidiabetic drugs (OR: 2.47, 95% CI: 2.04-2.99).
CONCLUSION
Our results indicate that antidiabetic drugs are generally safe to prescribe regarding the risk of DR among people with type 2 diabetes. Further robust and large-scale trials investigating the effects of insulin, meglitinides, and acarbose on DR are warranted.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=332052, identifier CRD42022332052.
Topics: Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Sodium-Glucose Transporter 2 Inhibitors; Acarbose; Dipeptidyl-Peptidase IV Inhibitors; Insulin; Glucagon-Like Peptide 1
PubMed: 38239984
DOI: 10.3389/fendo.2023.1303238 -
International Journal of Molecular... Apr 2023As the pathophysiologic mechanisms of type 2 diabetes mellitus (T2DM) are discovered, there is a switch from glucocentric to a more comprehensive, patient-centered... (Review)
Review
As the pathophysiologic mechanisms of type 2 diabetes mellitus (T2DM) are discovered, there is a switch from glucocentric to a more comprehensive, patient-centered management. The holistic approach considers the interlink between T2DM and its complications, finding the best therapies for minimizing the cardiovascular (CV) or renal risk and benefitting from the treatment's pleiotropic effects. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) fit best in the holistic approach because of their effects in reducing the risk of CV events and obtaining better metabolic control. Additionally, research on the SGLT-2i and GLP-1 RA modification of gut microbiota is accumulating. The microbiota plays a significant role in the relation between diet and CV disease because some intestinal bacteria lead to an increase in short-chain fatty acids (SCFA) and consequent positive effects. Thus, our review aims to describe the relation between antidiabetic non-insulin therapy (SGLT-2i and GLP-1 RA) with CV-proven benefits and the gut microbiota in patients with T2DM. We identified five randomized clinical trials including dapagliflozin, empagliflozin, liraglutide, and loxenatide, with different results. There were differences between empagliflozin and metformin regarding the effects on microbiota despite similar glucose control in both study groups. One study demonstrated that liraglutide induced gut microbiota alterations in patients with T2DM treated initially with metformin, but another failed to detect any differences when the same molecule was compared with sitagliptin. The established CV and renal protection that the SGLT-2i and GLP-1 RA exert could be partly due to their action on gut microbiota. The individual and cumulative effects of antidiabetic drugs on gut microbiota need further research.
Topics: Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Liraglutide; Sodium-Glucose Transporter 2 Inhibitors; Metformin; Cardiovascular Diseases; Microbiota; Glucagon-Like Peptide-1 Receptor
PubMed: 37108347
DOI: 10.3390/ijms24087184 -
Toxins Apr 2020Centipedes are among the oldest venomous arthropods that use their venom to subdue the prey. The major components of centipede venom are a variety of...
Centipedes are among the oldest venomous arthropods that use their venom to subdue the prey. The major components of centipede venom are a variety of low-molecular-weight peptide toxins that have evolved to target voltage-gated ion channels to interfere with the central system of prey and produce pain or paralysis for efficient hunting. Peptide toxins usually contain several intramolecular disulfide bonds, which confer chemical, thermal and biological stability. In addition, centipede peptides generally have novel structures and high potency and specificity and therefore hold great promise both as diagnostic tools and in the treatment of human disease. Here, we review the centipede peptide toxins with reported effects on ion channels, including Nav, Kv, Cav and the nonselective cation channel polymodal transient receptor potential vanilloid 1 (TRPV1).
Topics: Animals; Arthropod Proteins; Arthropod Venoms; Bites and Stings; Chilopoda; Drug Discovery; Humans; Ion Channels; Membrane Transport Modulators; Protein Conformation; Signal Transduction; Structure-Activity Relationship
PubMed: 32260499
DOI: 10.3390/toxins12040230 -
Acta Gastro-enterologica Belgica 2022Metabolic dysfunction-associated fatty liver disease (MAFLD) is the evidence of steatosis in the setting of a metabolic risk condition such as type 2 diabetes mellitus... (Review)
Review
Non-invasive screening, staging and management of metabolic dysfunction-associated fatty liver disease (MAFLD) in type 2 diabetes mellitus patients: what do we know so far ?
Metabolic dysfunction-associated fatty liver disease (MAFLD) is the evidence of steatosis in the setting of a metabolic risk condition such as type 2 diabetes mellitus (T2DM). Indeed, T2DM and liver steatosis share common pathophysiological mechanisms, and one can lead to the other. MAFLD can progress from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis as well as hepatocellular carcinoma (HCC). Because of the lack / disparity of guidelines for MAFLD screening, which is asymptomatic in its early stages, it is not rare that diabetic patients are belatedly diagnosed with NASH cirrhosis or HCC. We therefore recommend systematic non-invasive tests (NITs) that calculate an estimate of the risk based on readily available anthropometric and biological parameters. These include the fatty liver index (FLI) for steatosis detection and at least one of the following for fibrosis: non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4) or Hepamet fibrosis score (HFS). Indeed, NFS and FIB-4 are the best predictors of liver-related events, while FIB-4 and HFS correlate with overall mortality. Systematic literature review found only few retrospective or cross-sectional studies using NITs for systematic steatosis and fibrosis screening in T2DM patients, with a crucial need for prospective studies. This screening strategy will allow targeted patients to be referred for further liver investigation (e.g. ultrasound, elastometry) and care. Current treatment modalities of MAFLD in T2DM patients range from lifestyle and dietary interventions to specific glucose-lowering drugs that recently showed some benefits regarding MAFLD, such as pioglitazone, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Other treatments are currently under investigation.
Topics: Carcinoma, Hepatocellular; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Glucose; Humans; Liver Cirrhosis; Liver Neoplasms; Non-alcoholic Fatty Liver Disease; Prospective Studies; Retrospective Studies; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 35709779
DOI: 10.51821/85.2.9775 -
Clinics and Research in Hepatology and... 2022The efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease (NAFLD) in patients with and without type-2 diabetic patients (T2DM) remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease (NAFLD) in patients with and without type-2 diabetic patients (T2DM) remains unclear.
AIM
To conduct a meta-analysis to evaluate the efficacy of 3 novel glucose-lowering drug classes, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 (SGLT2) inhibitors, and dipeptidyl-peptidase-4 (DPP4) inhibitors on hepatic parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-Glutamyl Transferase (GGT), Bilirubin, and FIB-4 (Fibrosis).
METHODS
MEDLINE was searched from inception through October 2021 for randomized placebo or active glucose-lowering drug-controlled trials. A random-effects model was used to pool the results. A p-value of less than or equal to 0.05 was considered significant. Results were presented as weighted mean differences (WMD) and corresponding 95% confidence intervals (CIs).
RESULTS
Our pooled analysis consisted of 40 studies. A significant reduction was seen in AST with SGLT2 inhibitors (WMD = -2.31 IU/L, 95%CI: -3.16 to -1.47 IU/L, P < 0.00001) and GLP-1RA (WMD = -3.29 IU/L, 95%CI: -5.98 to -0.61 IU/L, P = 0.02). Similarly, significant reduction was seen in ALT with SGLT2 inhibitors (WMD = -5.93 IU/L, 95%CI: -7.70 to -4.16 IU/L, P < 0.00001) and GLP-1RAs (WMD = -9.92 IU/L, 95%CI: -19.89 to 0.05 IU/L, P = 0.05). In contrast, DPP-4 inhibitors showed no significant reduction in AST (WMD = -3.20 IU/L, 95%CI: -11.13 to 4.73 IU/L, P = 0.43) or ALT (WMD = -4.81 IU/L, 95%CI: -15.83 to 6.21 IU/L, P = 0.39). A significant reduction in GGT was seen with SGLT2 inhibitors (WMD = -6.49 IU/L, 95%CI: -11.09 to -1.89 IU/L, P = 0.006) and GLP-1RAs (WMD = -12.38 IU/L, 95%CI: -15.69 to -9.07 IU/L, P < 0.00001). However, significant results were not observed with DPP-4 inhibitors (WMD = -0.92 IU/L, 95%CI: -5.80 to 3.96 IU/L, P = 0.71). There was a statistically significant reduction in FIB-4 index with SGLT2 inhibitors (WMD = -0.21, 95%CI: -0.40 to -0.03, P = 0.02) and GLP-1 RA (WMD = -0.15, 95%CI: -0.29 to 0.00, P = 0.05). Lastly, SGLT2 inhibitors led to a significant change in bilirubin levels (WMD = 2.03, 95%CI: 0.76 to 3.30, P = 0.002) while the change in bilirubin was not significant with GLP-1 agonists (WMD = -0.21, 95%CI: -1.09 to 0.66, P = 0.63) and DPP-4 inhibitors (WMD = 0.14, 95%CI: -1.55 to 1.83, P = 0.87).
CONCLUSION
SGLT2 inhibitors and GLP-1 agonists have a beneficial effect on hepatic parameters in patients with NAFLD. However, further research is needed to evaluate the effect of DPP-4 inhibitors on hepatic function properly.
Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucose; Humans; Hypoglycemic Agents; Non-alcoholic Fatty Liver Disease; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 35659603
DOI: 10.1016/j.clinre.2022.101970 -
Pancreas Oct 2018The aim of this study was to evaluate the connection between pancreatic cancer (PC) and genetic variants associated with chronic pancreatitis via systematic review and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study was to evaluate the connection between pancreatic cancer (PC) and genetic variants associated with chronic pancreatitis via systematic review and meta-analysis.
METHODS
The data search was performed in 3 major databases (PubMed, Embase, and Cochrane Library). The selected studies have looked into the presence of the pancreatitis-associated genes in patients with PC and in control subjects, the outcome being the frequency of the mutations in the 2 groups. For the binary outcomes, pooled odds ratio (OR) and 95% confidence interval (CI) were calculated.
RESULTS
Ten articles proved to be eligible for the qualitative synthesis, and 8 articles were suitable for statistical analysis. Six case-control studies, comprising 929 PC cases and 1890 control subjects for serine protease inhibitor Kazal type 1 (SPINK1) mutations, and 5 case-control studies, comprising 1674 PC cases and 19,036 control subjects for CFTR mutations, were enrolled in our analysis. SPINK1 mutations showed no association with PC (OR, 1.52; 95% CI, 0.67-3.45; P = 0.315), whereas mutations in CFTR modestly increased the risk of PC (OR, 1.41; 95% CI, 1.07-1.84; P = 0.013).
CONCLUSION
Our meta-analysis showed that mutations in CFTR modestly increase the risk of PC, whereas no association was found between SPINK1 and PC.
Topics: Cystic Fibrosis Transmembrane Conductance Regulator; Genetic Predisposition to Disease; Humans; Mutation; Odds Ratio; Pancreatic Neoplasms; Pancreatitis, Chronic; Risk Factors; Trypsin Inhibitor, Kazal Pancreatic
PubMed: 30134356
DOI: 10.1097/MPA.0000000000001145