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Diabetic Medicine : a Journal of the... Mar 2022To compare the cardiovascular, renal and safety outcomes of second-line glucose-lowering agents used in the management of people with type 2 diabetes. (Comparative Study)
Comparative Study Meta-Analysis
Comparative effectiveness of cardiovascular, renal and safety outcomes of second-line antidiabetic drugs use in people with type 2 diabetes: A systematic review and network meta-analysis of randomised controlled trials.
AIMS
To compare the cardiovascular, renal and safety outcomes of second-line glucose-lowering agents used in the management of people with type 2 diabetes.
METHODS
MEDLINE, EMBASE and CENTRAL were searched from inception to 13 July 2021 for randomised controlled trials comparing second-line glucose lowering therapies with placebo, standard care or one another. Primary outcomes included cardiovascular and renal outcomes. Secondary outcomes were non-cardiovascular adverse events. Risk ratios (RRs) and corresponding confidence intervals (CI) or credible intervals (CrI) were reported within pairwise and network meta-analysis. The quality of evidence was evaluated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) criteria. Number needed to treat (NNT) and number needed (NNH) to harm were calculated at 5 years using incidence rates and RRs. PROSPERO (CRD42020168322).
RESULTS
We included 38 trials from seven classes of glucose-lowering therapies. Both sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1RA) showed moderate to high certainty in reducing risk of 3-point major adverse cardiovascular events, 3P-MACE (network estimates: SGLT2i [RR 0.90; 95% CrI 0.84-0.96; NNT, 59], GLP1RA [RR 0.88; 95% CrI 0.83-0.93; NNT, 50]), cardiovascular death, all-cause mortality, renal composite outcome and macroalbuminuria. SGLT2i also showed high certainty in reducing risk of hospitalization for heart failure (hHF), ESRD, acute kidney injury, doubling in serum creatinine and decline in eGFR. GLP1RA were associated with lower risk of stroke (high certainty) while glitazone use was associated with an increased risk of hHF (very low certainty). The risk of developing ESRD was lower with the use of sulphonylureas (low certainty). For adverse events, sulphonylureas and insulin were associated with increased hypoglycaemic events (very low to low certainty), while GLP1RA increased the risk of gastrointestinal side effects leading to treatment discontinuation (low certainty). DPP-4i increased risk of acute pancreatitis (low certainty). SGLT2i were associated with increased risk of genital infection, volume depletion (high certainty), amputation and ketoacidosis (moderate certainty). Risk of fracture was increased with the use of glitazones (moderate certainty).
CONCLUSIONS
SGLT2i and GLP1RA were associated with lower risk for different cardiorenal end points, when used as an adjunct to metformin in people with type 2 diabetes. Additionally, SGLT2i demonstrated benefits in reducing risk for surrogate end points in kidney disease progression. Safety outcomes differ among the available pharmacotherapies.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Insulin; Kidney Diseases; Metformin; Network Meta-Analysis; Pancreatitis; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors; Sulfonylurea Compounds; Thiazolidinediones
PubMed: 34962662
DOI: 10.1111/dme.14780 -
The Lancet. Diabetes & Endocrinology Mar 2020Considering the global burden of diabetes and associated cardiovascular disease, an urgent need exists for the best treatment, which should be based on the best... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Considering the global burden of diabetes and associated cardiovascular disease, an urgent need exists for the best treatment, which should be based on the best available evidence. We examined the association between glucose-lowering medications and a broad range of cardiovascular outcomes, and assessed the strength of evidence for these associations.
METHODS
For this umbrella review we searched PubMed, Embase, and the Cochrane Library to identify systematic reviews and meta-analyses of randomised controlled trials examining the cardiovascular safety of glucose-lowering medications. Cardiovascular outcomes examined included major adverse cardiovascular events, cardiovascular death, myocardial infarction, stroke, heart failure, unstable angina, and atrial fibrillation. For each meta-analysis, we estimated the relative risk (RR) and 95% CI. We also created an evidence map showing the plausible benefits or harms of each intervention and the certainty of the evidence.
FINDINGS
We examined 232 meta-analyses evaluating ten classes of diabetes drugs. We identified six risk and 38 protective associations showing a high strength of evidence. Six associations increased the risk of cardiovascular disease, including glimepiride (stroke [RR 2·01; 95% CI 1·02-3·98]), rosiglitazone (myocardial infarction [1·28; 1·02-1·62] and heart failure [1·72, 1·31-2·27]), and pioglitazone (heart failure [1·40; 1·16-1·69]). 38 associations decreased the risk of cardiovascular disease, including glucagon-like peptide-1 receptor agonists as a class (major adverse cardiovascular events [RR 0·88; 95% CI 0·84-0·92], death from cardiovascular disease [0·87; 0·81-0·94], myocardial infarction [0·92; 0·86-0·99], stroke [0·84; 0·77-0·93], and heart failure [0·90; 0·83-0·99]), albiglutide (major adverse cardiovascular events [0·81; 0·68-0·96], myocardial infarction [0·77; 0·64-0·92], and heart failure [0·71; 0·55-0·93]), dulaglutide (stroke [0·78; 0·64-0·96]), exenatide (major adverse cardiovascular events [0·91; 0·83-1·00]), liraglutide (major adverse cardiovascular events [0·86; 0·77-0·96]), semaglutide (major adverse cardiovascular events [0·76; 0·62-0·92] and stroke [0·67; 0·45-1·00]), sodium-glucose co-transporter-2 inhibitors as a class (major adverse cardiovascular events [0·87; 0·82-0·93], death from cardiovascular disease [0·82; 0·75-0·90], myocardial infarction [0·86; 0·78-0·94], and heart failure [0·68; 0·63-0·73]), canagliflozin (major adverse cardiovascular events [0·84; 0·75-0·93], death from cardiovascular disease [0·82; 0·71-0·96], and heart failure [0·65; 0·54-0·78]), dapagliflozin (heart failure [0·70; 0·60-0·82]), empagliflozin (major adverse cardiovascular events [0·85; 0·77-0·94], death from cardiovascular disease [0·62; 0·50-0·78], and heart failure [0·64; 0·53-0·77]), and pioglitazone (major adverse cardiovascular events [0·84; 0·74-0·96], myocardial infarction [0·80; 0·67-0·95], and stroke [0·79; 0·65-0·95]).
INTERPRETATION
We found varied levels of evidence for the associations between diabetes drugs and cardiovascular outcomes; some drugs raised the risk of cardiovascular disease, whereas others showed benefit.
FUNDING
None.
Topics: Cardiovascular Diseases; Diabetes Mellitus; Humans; Hypoglycemic Agents; Incidence; Meta-Analysis as Topic; Prognosis
PubMed: 32006518
DOI: 10.1016/S2213-8587(19)30422-X -
International Journal of Molecular... Jun 2023The increase in life expectancy without a decrease in the years lived without disability leads to the rise of the population aged over 65 years prone to polypharmacy.... (Meta-Analysis)
Meta-Analysis Review
The increase in life expectancy without a decrease in the years lived without disability leads to the rise of the population aged over 65 years prone to polypharmacy. The novel antidiabetic drugs can improve this global therapeutic and health problem in patients with diabetes mellitus (DM). We aimed to establish the efficacy (A1c hemoglobin reduction) and safety of the newest antidiabetic drugs (considered so due to their novelty in medical practice use), specifically DPP-4i, SGLT-2i, GLP-1 Ra, and tirzepatide. The present meta-analysis followed the protocol registered at Prospero with the CRD42022330442 registration number. The reduction in HbA1c in the DPP4-i class for tenegliptin was 95% CI -0.54 [-1.1, 0.01], = 0.06; in the SGLT2-iclass for ipragliflozin 95% CI -0.2 [-0.87, 0.47], = 0.55; and for tofogliflozin 95% CI 3.13 [-12.02, 18.28], = 0.69, while for tirzepatide it was 0.15, 95% CI [-0.50, 0.80] ( = 0.65). The guidelines for treatment in type 2 DM are provided from cardiovascular outcome trials that report mainly major adverse cardiovascular events and data about efficacy. The newest antidiabetic non-insulinic drugs are reported to be efficient in lowering HbA1c, but this effect depends between classes, molecules, or patients' age. The newest antidiabetic drugs are proven to be efficient molecules in terms of HbA1c decrease, weight reduction, and safety, but more studies are needed in order to characterize exactly their efficacy and safety profiles.
Topics: Humans; Aged; Hypoglycemic Agents; Glycated Hemoglobin; Dipeptidyl-Peptidase IV Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor
PubMed: 37298707
DOI: 10.3390/ijms24119760 -
Clinical Pharmacokinetics Nov 2022An ever-growing body of evidence supports the impact of cytokine modulation on the patient's phenotypic drug response. The aim of this systematic review was to analyze... (Review)
Review
The Cytokine Release Syndrome and/or the Proinflammatory Cytokines as Underlying Mechanisms of Downregulation of Drug Metabolism and Drug Transport: A Systematic Review of the Clinical Pharmacokinetics of Victim Drugs of this Drug-Disease Interaction Under Different Clinical Conditions.
BACKGROUND AND OBJECTIVE
An ever-growing body of evidence supports the impact of cytokine modulation on the patient's phenotypic drug response. The aim of this systematic review was to analyze the clinical studies that assessed the pharmacokinetics of victim drugs of this drug-disease interaction in the presence of different scenarios of cytokine modulation in comparison with baseline conditions.
METHODS
We conducted a systematic review by searching the PubMed-MEDLINE database from inception until February 2022 to retrieve prospective and/or retrospective observational studies, population pharmacokinetic studies, phase I studies, and/or case series/reports that investigated the impact of cytokine modulation on the pharmacokinetic behavior of victim drugs. Only studies providing quantitative pharmacokinetic data of victim drugs by comparing normal status versus clinical conditions with documented cytokine modulation or by assessing the influence of anti-inflammatory biological agents on metabolism and/or transport of victim drugs were included.
RESULTS
Overall, 26 studies were included. Rheumatoid arthritis (6/26; 23.1%) and sepsis (5/26; 19.2%) were the two most frequently investigated pro-inflammatory clinical scenarios. The victim drug most frequently assessed was midazolam (14/26; 53.8%; as a probe for cytochrome P450 [CYP] 3A4). Cytokine modulation showed a moderate inhibitory effect on CYP3A4-mediated metabolism (area under the concentration-time curve increase and/or clearance decrease between 1.98-fold and 2.59-fold) and a weak-to-moderate inhibitory effect on CYP1A2, CYP2C9, and CYP2C19-mediated metabolism (in the area under the concentration-time curve increase or clearance decrease between 1.29-fold and 1.97-fold). Anti-interleukin-6 agents showed remarkable activity in counteracting downregulation of CYP3A4-mediated activity (increase in the area under the concentration-time curve between 1.75-fold and 2.56-fold).
CONCLUSIONS
Cytokine modulation may cause moderate or weak-to-moderate downregulation of metabolism/transport of victim drugs, and this may theoretically have relevant clinical consequences.
Topics: Humans; Cytochrome P-450 CYP3A; Cytokine Release Syndrome; Cytokines; Down-Regulation; Prospective Studies; Retrospective Studies; Drug Interactions
PubMed: 36059001
DOI: 10.1007/s40262-022-01173-8 -
Advances in Therapy Oct 2023Evidence from cardiovascular outcome trials (CVOTs) for newer antidiabetic drugs is increasingly influencing revised recommendations for second-line therapy in type 2... (Review)
Review
INTRODUCTION
Evidence from cardiovascular outcome trials (CVOTs) for newer antidiabetic drugs is increasingly influencing revised recommendations for second-line therapy in type 2 diabetes (T2D). This systematic review aimed to compare the cost-effectiveness of newer antidiabetic drugs specified as sodium-glucose cotransporter 2 inhibitor (SGLT2i), glucagon-like peptide 1 receptor agonist (GLP-1RA), and dipeptidyl peptidase 4 inhibitor (DPP-4i) for T2D in a second-line setting.
METHODS
A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, and all relevant published studies were searched comprehensively in electronic databases, including PubMed, Embase, Web of Science, and International Health Technology Assessment database published from April 2023. The quality of the included studies was evaluated using Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 reporting checklists.
RESULTS
We included 28 studies that met the inclusion criteria. Overall reporting of the identified studies largely met CHEERS 2022 recommendations. The CORE and Cardiff models were the most frequently utilized for pharmacoeconomic evaluation in T2D. Four studies consistently discovered that SGLT2i was more cost-effective than GLP-1RA in T2D who were not adequately controlled by metformin monotherapy. Four studies compared GLP-1RA with DPP-4i, sufonylurea (SU), or insulin. Except for one that demonstrated SU was cost-effective, all were GLP-1RA. Five studies revealed that SGLT2i was more cost-effective than DPP-4i or SU. Eleven studies indicated that DPP-4i was more cost-effective than traditional antidiabetic drugs. Four additional studies explored the cost-effectiveness of various antidiabetic drugs as second-line options, indicating that SU, SGLT2i, or meglitinides were more economically advantageous. The most common driven factors were the cost of new antidiabetic drugs.
CONCLUSION
Newer antidiabetic drugs as second line are the cost-effective option for T2D from the cost-effectiveness perspective, especially SGLT2i.
Topics: Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Cost-Benefit Analysis; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Glucagon-Like Peptide-1 Receptor
PubMed: 37515713
DOI: 10.1007/s12325-023-02612-z -
Journal of Sports Sciences Feb 2020High-intensity-interval-training (HIIT) has been suggested to have beneficial effects in multiple populations across individual systematic reviews, although there is a... (Meta-Analysis)
Meta-Analysis
High-intensity-interval-training (HIIT) has been suggested to have beneficial effects in multiple populations across individual systematic reviews, although there is a lack of clarity in the totality of the evidence whether HIIT is effective and safe across different populations and outcomes. The aim of this meta-review was to establish the benefits, safety and adherence of HIIT interventions across all populations from systematic reviews and meta-analyses. Major databases were searched for systematic reviews (with/without meta-analyses) of randomised & non-randomised trials that compared HIIT to a control. Thirty-three systematic reviews (including 25 meta-analyses) were retrieved encompassing healthy subjects and people with physical health complications. Evidence suggested HIIT improved cardiorespiratory fitness, anthropometric measures, blood glucose and glycaemic control, arterial compliance and vascular function, cardiac function, heart rate, some inflammatory markers, exercise capacity and muscle mass, versus non-active controls. Compared to active controls, HIIT improved cardiorespiratory fitness, some inflammatory markers and muscle structure. Improvements in anxiety and depression were seen compared to pre-training. Additionally, no acute injuries were reported, and mean adherence rates surpassed 80% in most systematic reviews. Thus, HIIT is associated with multiple benefits. Further large-scale high-quality studies are needed to reaffirm and expand these findings. ACSM: American College of Sports Medicine; BMI: Body Mass Index; BNP: Brain Natriuretic Peptide; BP: Blood Pressure; CAD: Coronary Artery Disease; CHD: Coronary Heart Disease; COPD: Chronic Obstructive Pulmonary Disease; CRP: c- reactive Protein; CVD: Cardiovascular Disease; DBP: Diastolic Blood Pressure; ES: Effect Size; FAS: Reduced Fatty Acid Synthase; FATP-1: Reduced Fatty Acid Transport Protein 1; FMD: Flow Mediated Dilation; Hs-CRP: High-sensitivity c- reactive Protein; HDL: High Density Lipoprotein; HIIT: High-Intensity Interval Training; HOMA: Homoeostatic Model Assessment; HR: Heart Rate; HTx: Heart Transplant Recipients; IL-6: Interleukin-6; LDL: Low Density Lipoprotein; LV: Left Ventricular; LVEF: Left Ventricular Ejection Fraction; MD: Mean Difference; MetS: Metabolic Syndrome; MPO: Myeloperoxidase; MICT: Moderate-Intensity Continuous Training; NO: Nitric Oxide; NRCT: Non-Randomised Controlled Trial; PA: Physical Activity; PAI-1: Plasminogen-activator-inhibitor-1; QoL: Quality of Life; RCT: Randomised Controlled Trial; RoB: Risk of Bias; RPP: Rate Pressure Product; RT: Resistance Training; SBP: Systolic Blood Pressure; SD: Standardised Difference; SMD: Standardised Mean Difference; TAU: Treatment-As-Usual; T2DM: Type 2 Diabetes Mellitus; TC: Total Cholesterol; TG: Triglycerides; TNF-alfa: Tumour Necrosis Factor alpha; UMD: Unstandardised Mean Difference; WC: Waist Circumference; WHR: Waist-to-Hip Ratio; WMD: Weighted Mean Difference: HIIT may improve cardiorespiratory fitness, cardiovascular function, anthropometric variables, exercise capacity, muscular structure and function, and anxiety and depression severity in healthy individuals and those with physical health disorders.Additionally, HIIT appears to be safe and does not seem to be associated with acute injuries or serious cardiovascular events.
Topics: Anthropometry; Anxiety; Biomarkers; Cardiorespiratory Fitness; Depression; Exercise Tolerance; High-Intensity Interval Training; Humans; Inflammation; Mental Health; Muscle, Skeletal; Quality of Life
PubMed: 31889469
DOI: 10.1080/02640414.2019.1706829 -
Medicine Jul 2021Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been demonstrated to be able to improve the... (Meta-Analysis)
Meta-Analysis
Comparative efficacy of 5 sodium glucose cotransporter 2 inhibitor and 7 glucagon-like peptide 1 receptor agonists interventions on cardiorenal outcomes in type 2 diabetes patients: A network meta-analysis based on cardiovascular or renal outcome trials.
BACKGROUND
Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been demonstrated to be able to improve the cardiovascular and renal prognosis in patients with type 2 diabetes (T2D). However, the relative efficacy of various SGLT2 inhibitors and GLP-1 RAs on cardiorenal outcomes is unestablished.
METHODS
We searched PubMed and Embase for relevant cardiovascular or renal outcome trials (CVOTs). Endpoints of interest were major adverse cardiovascular events (MACE), stroke, myocardial infarction (MI), cardiovascular death (CVD), all-cause death (ACD), kidney function progression (KFP), and hospitalization for heart failure (HHF). Bayesian network meta-analysis was conducted to produce pooled hazard ratio (HR) and 95% confidence interval (CI). We calculated the probability values of surface under the cumulative ranking curve to rank active and placebo interventions.
RESULTS
Fourteen COVTs were included in analysis. Sotagliflozin (HR 0.76, 95% CI 0.61-0.94), subcutaneous semaglutide, and albiglutide lowered MACE versus lixisenatide among others. Sotagliflozin (HR 0.59, 95% CI 0.40-0.89), canagliflozin, and empagliflozin lowered HHF versus subcutaneous semaglutide among others. Dapagliflozin and empagliflozin lowered KFP versus exenatide among others. Empagliflozin and oral semaglutide lowered CVD versus dapagliflozin among others. Sotagliflozin (HR 0.65, 95% CI 0.47-0.91) and albiglutide lowered MI versus ertugliflozin among others. Sotagliflozin (HR 0.56, 95% CI 0.37-0.85) and subcutaneous semaglutide lowered stroke versus empagliflozin among others. Oral semaglutide and empagliflozin lowered ACD versus subcutaneous semaglutide among others. The maximum surface under the cumulative ranking curve values followed sotagliflozin, subcutaneous semaglutide, and albiglutide in lowering MACE; sotagliflozin, canagliflozin, and empagliflozin in lowering HHF; dapagliflozin and empagliflozin in lowering KFP; empagliflozin and oral semaglutide in lowering CVD; sotagliflozin and albiglutide in lowering MI; sotagliflozin and subcutaneous semaglutide in lowering stroke; and oral semaglutide and empagliflozin in lowering ACD.
CONCLUSIONS
This updated network meta-analysis reproduced the findings in the first network meta-analysis, and moreover revealed that sotagliflozin was one of the most effective drugs as for lowering MI, stroke, MACE, and HHF, whereas ertugliflozin was not. These findings will provide the according evidence regarding the usage of specific SGLT2 inhibitors and GLP-1 RAs in T2D patients for prevention of specific cardiorenal endpoints.
Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Heart; Humans; Kidney; Network Meta-Analysis; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome
PubMed: 34397684
DOI: 10.1097/MD.0000000000026431 -
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 -
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 -
Critical Reviews in Food Science and... 2022Lactoferrin (Lf), a bioactive protein initially found in many biological secretions including milk, is regarded as the nutritional supplement or therapeutic ligand due...
Lactoferrin (Lf), a bioactive protein initially found in many biological secretions including milk, is regarded as the nutritional supplement or therapeutic ligand due to its multiple functions. Research on its mode of action reveals that intact Lf or its active peptide (i.e., lactoferricin) shows an important multifunctional performance. Oral delivery is considered as the most convenient administration route for this bioactive protein. Unfortunately, Lf is sensitive to the gastrointestinal (GI) physicochemical stresses and lactoferricin is undetectable in GI digesta. This review introduces the functionality of Lf at the molecular level and its degradation behavior in GI tract is discussed in detail. Subsequently, the absorption and transport of Lf from intestine into the blood circulation, which is pivotal to its health promoting effects in various tissues, and some assisting labeling methods are discussed. Stabilization technologies aiming at preserving the structural integrity and functional properties of orally administrated Lf are summarized and compared. Altogether, this work comprehensively reviews the structure-function relationship of Lf, its oral fate and the development of stabilization technologies for the enhancement of the oral bioavailability of Lf. The existing limitations and scope for future research are also discussed.
Topics: Animals; Chemical Phenomena; Gastrointestinal Tract; Lactoferrin; Milk
PubMed: 33749401
DOI: 10.1080/10408398.2021.1900774