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International Journal of... Apr 2024The current meta-analysis aims to explore the potential correlation between natural resistance-associated macrophage protein 1 (NRAMP1) (3'-Untranslated region [3'-UTR])... (Meta-Analysis)
Meta-Analysis Review
A Systemic Review and Meta-analysis on Natural Resistance-associated Macrophage Protein 1 (3'-Untranslated Region) and Nucleotide-binding Oligomerization Domain-2 (rs8057341) Polymorphisms and Leprosy Susceptibility in Asian and Caucasian Populations.
The current meta-analysis aims to explore the potential correlation between natural resistance-associated macrophage protein 1 (NRAMP1) (3'-Untranslated region [3'-UTR]) and nucleotide-binding oligomerization domain-2 (NOD2 [rs8057341]) gene polymorphisms and their association with leprosy susceptibility in both Asian and Caucasian populations. Datas were retrieved from case control studies with NOD 2 and NRAMP 1 gene polymorphism associated with leprosy disease. Leprosy emerges as a particularly distinctive ailment among women on a global scale. The NRAMP1 (3'-UTR) and NOD2 (rs8057341) genetic variations play a crucial role in the progression of leprosy. A systematic review of relevant case-control studies was conducted across several databases, including ScienceDirect, PubMed, Google Scholar, and Embase. Utilizing MetaGenyo and Review Manager 5.4 Version, statistical analyses were carried out. Nine case-control studies totaling 3281 controls and 3062 leprosy patients are included in the research, with the objective of examining the potential association between NRAMP1 (3'-UTR) and NOD2 (rs8057341) gene polymorphisms and leprosy risk. The review methodology was registered in PROSPERO (ID520883). The findings reveal a robust association between NRAMP1 (3'-UTR) and NOD2 (rs8057341) gene polymorphisms and leprosy risk across various genetic models. Although the funnel plot analysis did not identify publication bias, bolstering these findings and elucidating potential gene-gene and gene-environment interactions require further comprehensive epidemiological research. This study identified a strong correlation between polymorphisms in the NOD2 (rs8057341) genes and susceptibility to leprosy across two genetic models. Further comprehensive epidemiological investigations are warranted to validate these findings and explore potential interactions between these genes and environmental factors.
Topics: Humans; Leprosy; Genetic Predisposition to Disease; Asian People; White People; Cation Transport Proteins; Nod2 Signaling Adaptor Protein; 3' Untranslated Regions; Polymorphism, Single Nucleotide; Case-Control Studies; Female; Polymorphism, Genetic; Male
PubMed: 38916380
DOI: 10.4103/ijmy.ijmy_43_24 -
International Journal of Cardiology Sep 2024Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are anti-hyperglycemic drugs and have been proven to have cardiovascular protective effects for patients with heart... (Meta-Analysis)
Meta-Analysis
Effect of sodium-glucose co-transporter 2 inhibitors (SGLT2i) on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and structural changes following myocardial infarction: A systematic review and meta-analysis.
BACKGROUND
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are anti-hyperglycemic drugs and have been proven to have cardiovascular protective effects for patients with heart failure regardless of their diabetes status. However, the benefit of SGLT2i following myocardial infarction (MI) remains incompletely established. This review aimed to investigate the impact of SGLT2i on NT-proBNP levels and structural changes post-MI.
METHOD
Medline, ClinicalTrial.gov, Scopus, and Directory of open-access journals were searched to retrieve the relevant articles. Eligible studies were randomized clinical trials that assessed NT-proBNP and cardiac structural changes in patients who received SGLT2i compared to placebo following MI. Two reviewers independently screened articles, extracted data, and assessed study quality.
RESULT
Four studies were included in this review, including patients with and without diabetes. While two studies showed no marked decrease from the baseline in NT-proBNP levels between the SGLT2i group and the control group, two studies reported a substantial reduction. The meta-analysis included three of these studies, with a total of 238 participants. The meta-analysis did not find a statistically significant drop in NT-proBNP levels post-MI in the SGLT2 inhibitors group compared to placebo (pooled SMD = 0.16, 95% CI 0.57-0.26, P 0.45). Furthermore, different echocardiographic parameters were reported in the included trials, yet no meta-analysis could be conducted to assess the influence of SGLT2i on cardiac remodeling post-MI.
CONCLUSION
SGLT2i did not result in a statistically significant reduction of NT-proBNP level subsequent to myocardial infarction. A knowledge gap exists regarding the impact of these agents on cardiac remodeling post-MI. Future high-quality clinical trials are needed to provide more robust evidence.
Topics: Humans; Natriuretic Peptide, Brain; Sodium-Glucose Transporter 2 Inhibitors; Peptide Fragments; Myocardial Infarction; Randomized Controlled Trials as Topic; Biomarkers; Diabetes Mellitus, Type 2; Treatment Outcome
PubMed: 38852858
DOI: 10.1016/j.ijcard.2024.132239 -
Cardiovascular Diabetology Jun 2024
Correction to: Effectiveness and safety of the combination of sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies.
PubMed: 38824524
DOI: 10.1186/s12933-024-02283-2 -
Journal of Alzheimer's Disease Reports 2024Alzheimer's disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in...
BACKGROUND
Alzheimer's disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in targeting core AD pathology, clinical studies are limited.
OBJECTIVE
A systematic review was performed to evaluate GLP-1 RAs in AD for their potential to target core AD pathology and improve cognition.
METHODS
Searches were conducted via three different databases (PubMed, Embase, and Cochrane Library). Search terms included Medical Subject Headings (MeSH) terms: 'glucagon-like peptide 1 receptor agonist' and 'Alzheimer's disease', as well as entry terms 'GLP-1 RA', 'AD', and three types of GLP-1 RA: 'liraglutide', 'exenatide', and 'lixisenatide'.
RESULTS
A total of 1,444 studies were screened. Six articles that met criteria were included (four randomized control trials [RCTs] and two protocol studies). Two RCTs with amyloid-β and tau biomarker endpoints did not observe an end of treatment difference between the placebo and treated groups. In three RCTs with cognitive endpoints, there was no end of treatment difference between placebo and treated groups. GLP-1 RA showed metabolic benefits, such as lower body mass index and improved glucose levels on oral glucose tolerance tests in treated groups. GLP-1 RA may mitigate the decline in cerebral glucose metabolism and show enhanced blood-brain glucose transport capacity using F-FDG PET, however, more data is needed.
CONCLUSIONS
GLP-1 RA therapy did not alter amyloid-β and tau biomarkers nor show improvements in cognition but showed potential metabolic and neuroprotective benefits.
PubMed: 38746639
DOI: 10.3233/ADR-230181 -
Revista Brasileira de Psiquiatria (Sao... 2024Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood...
OBJECTIVES
Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood biomarkers have also been observed; however, studies evaluating the potential relationship between brain alterations and the periphery are scarce. The objective of this systematic review is to investigate the relationship between blood-based biomarkers and WM in BD.
METHODS
PubMed, Embase, and PsycINFO were used to conduct literature searches. Cross-sectional or longitudinal studies reporting original data which investigated both a blood-based biomarker and WM (by neuroimaging) in BD were included.
RESULTS
Of 3,750 studies retrieved, 23 were included. Several classes of biomarkers were found to have a significant relationship with WM in BD. These included cytokines and growth factors (interleukin-8 [IL-8], tumor necrosis factor alpha [TNF-a], and insulin-like growth factor binding protein 3 [IGFBP-3]), innate immune system (natural killer cells [NK]), metabolic markers (lipid hydroperoxidase, cholesterol, triglycerides), the kynurenine (Kyn) pathway (5-hydroxyindoleacetic acid, kynurenic acid [Kyna]), and various gene polymorphisms (serotonin-transporter-linked promoter region).
CONCLUSION
This systematic review revealed that blood-based biomarkers are associated with markers of WM deficits observed in BD. Longitudinal studies investigating the potential clinical utility of these specific biomarkers are encouraged.
Topics: Bipolar Disorder; Humans; Biomarkers; White Matter; Myelin Sheath; Cytokines
PubMed: 38712923
DOI: 10.47626/1516-4446-2023-3267 -
Annals of Internal Medicine May 2024Newer diabetes medications may have beneficial effects on mortality, cardiovascular outcomes, and renal outcomes. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Newer diabetes medications may have beneficial effects on mortality, cardiovascular outcomes, and renal outcomes.
PURPOSE
To evaluate the effectiveness, comparative effectiveness, and harms of sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP1) agonists, dipeptidyl peptidase-4 (DPP4) inhibitors, and long-acting insulins as monotherapy or combination therapy in adults with type 2 diabetes mellitus (T2DM).
DATA SOURCES
MEDLINE and EMBASE for randomized controlled trials (RCTs) published from 2010 through January 2023.
STUDY SELECTION
RCTs lasting at least 52 weeks that included at least 500 adults with T2DM receiving eligible medications and reported any outcomes of interest.
DATA EXTRACTION
Data were abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE) were done.
DATA SYNTHESIS
A total of 130 publications from 84 RCTs were identified. CoE was appraised using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria for direct, indirect, and network meta-analysis (NMA); the highest CoE was reported. Compared with usual care, SGLT2 inhibitors and GLP1 agonists reduce all-cause mortality (high CoE) and major adverse cardiovascular events (MACE) (moderate to high CoE), SGLT2 inhibitors reduce progression of chronic kidney disease (CKD) and heart failure hospitalizations and GLP1 agonists reduce stroke (high CoE), and SGLT2 inhibitors reduce serious adverse events and severe hypoglycemia (high CoE). The threshold for minimally important differences, which was predefined with the American College of Physicians Clinical Guidelines Committee, was not met for these outcomes. Compared with usual care, insulin, tirzepatide, and DPP4 inhibitors do not reduce all-cause mortality (low to high CoE). Compared with insulin, SGLT2 inhibitors and GLP1 agonists reduce all-cause mortality (low to moderate CoE). Compared with DPP4 inhibitors, GLP1 agonists reduce all-cause mortality (moderate CoE). Compared with DPP4 inhibitors and sulfonylurea (SU), SGLT2 inhibitors reduce MACE (moderate to high CoE). Compared with SU and insulin, SGLT2 inhibitors and GLP1 agonists reduce severe hypoglycemia (low to high CoE).
LIMITATIONS
Infrequent direct comparisons between drugs of interest; sparse data for NMA on most outcomes; possible incoherence due to differences in baseline patient characteristics and usual care; insufficient data on predefined subgroups, including demographic subgroups, patients with prior cardiovascular disease, and treatment-naive persons.
CONCLUSION
In adults with T2DM, SGLT2 inhibitors and GLP1 agonists (but not DPP4 inhibitors, insulin, or tirzepatide) reduce all-cause mortality and MACE compared with usual care. SGLT2 inhibitors reduce CKD progression and heart failure hospitalization and GLP1 agonists reduce stroke compared with usual care. Serious adverse events and severe hypoglycemia are less frequent with SGLT2 inhibitors and GLP1 agonists than with insulin or SU.
PRIMARY FUNDING SOURCE
American College of Physicians. (PROSPERO: CRD42022322129).
Topics: Humans; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemic Agents; Network Meta-Analysis; Insulin; Adult; Cardiovascular Diseases; Glucagon-Like Peptide 1; Hypoglycemia; Drug Therapy, Combination
PubMed: 38639549
DOI: 10.7326/M23-1490 -
Annals of Internal Medicine May 2024In the United States, costs of antidiabetes medications exceed $327 billion. (Review)
Review
Cost-Effectiveness of Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review of Cost-Effectiveness Studies for the American College of Physicians.
BACKGROUND
In the United States, costs of antidiabetes medications exceed $327 billion.
PURPOSE
To systematically review cost-effectiveness analyses (CEAs) of newer antidiabetes medications for type 2 diabetes.
DATA SOURCES
Bibliographic databases from 1 January 2010 through 13 July 2023, limited to English.
STUDY SELECTION
Nonindustry-funded CEAs, done from a U.S. perspective that estimated cost per quality-adjusted life-year (QALY) gained for newer antidiabetic medications. Two reviewers screened the literature; disagreements were resolved with a third reviewer.
DATA EXTRACTION
Cost-effectiveness analyses were reviewed for treatment comparisons, model inputs, and outcomes. Risk of bias (RoB) of the CEAs was assessed using Drummond criteria and certainty of evidence (CoE) was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluations). Certainty of evidence was determined using cost per QALY thresholds predetermined by the American College of Physicians Clinical Guidelines Committee; low (>$150 000), intermediate ($50 to $150 000), or high (<$50 000) value per QALY compared with the alternative.
DATA SYNTHESIS
Nine CEAs were eligible (2 low, 1 high, and 6 some concerns RoB), evaluating glucagon-like peptide-1 agonists (GLP1a), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucose-dependent insulinotropic peptide agonist (GIP/GLP1a), and insulin. Comparators were metformin, sulfonylureas, neutral protamine Hagedorn (NPH) insulin, and others. Compared with metformin, GLP1a and SGLT2i are low value as first-line therapy (high CoE) but may be of intermediate value when added to metformin or background therapy compared with adding nothing (low CoE). Insulin analogues may be similarly effective but more expensive than NPH insulin (low CoE). The GIP/GLP1a value is uncertain (insufficient CoE).
LIMITATIONS
Cost-effectiveness analyses varied in methodological approach, assumptions, and drug comparisons. Risk of bias and GRADE method for CEAs are not well established.
CONCLUSION
Glucagon-like peptide-1 agonists and SGLT2i are of low value as first-line therapy but may be of intermediate value when added to metformin or other background therapy compared with adding nothing. Other drugs and comparisons are of low or uncertain value. Results are sensitive to drug effectiveness and cost assumptions.
PRIMARY FUNDING SOURCE
American College of Physicians. (PROSPERO: CRD42022382315).
Topics: Diabetes Mellitus, Type 2; Humans; Cost-Benefit Analysis; Hypoglycemic Agents; Quality-Adjusted Life Years; United States; Dipeptidyl-Peptidase IV Inhibitors; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38639547
DOI: 10.7326/M23-1492 -
PloS One 2024An important cellular barrier to maintain the stability of the brain's internal and external environment is the blood-brain barrier (BBB). It also prevents harmful... (Meta-Analysis)
Meta-Analysis
Electroacupuncture stimulation enhances the permeability of the blood-brain barrier: A systematic review and meta-analysis of preclinical evidence and possible mechanisms.
An important cellular barrier to maintain the stability of the brain's internal and external environment is the blood-brain barrier (BBB). It also prevents harmful substances from entering brain tissue through blood circulation while providing protection for the central nervous system. It should be noted, however, that the intact BBB can be a barrier to the transport of most drugs into the brain via the conventional route of administration, which can prevent them from reaching effective concentrations for the treatment of disorders affecting the central nervous system. Electroacupuncture stimulation has been shown to be effective at opening the BBB in a series of experimental studies. This study systematically analyzes the possibility and mechanism by which electroacupuncture opens the BBB. In PubMed, Web of Science, VIP Database, Wanfang Database, and the Chinese National Knowledge Infrastructure, papers have been published for nearly 22 years aimed at opening the BBB and its associated structures. A comparison of EB content between electroacupuncture and control was selected as the primary outcome. There were also results on vascular endothelial growth factor (VEGF), nerve growth factor (NGF), P-Glycoprotein (P-gp), Matrix Metalloproteinase 9 (MMP-9), and glial fibrillary acidic protein (GFAP). We utilized Review Manager software analysis to analyze correlations between studies with a view to exploring the mechanisms of similarity. Evans Blue infiltration forest plot: pooled effect size of 2.04, 95% CI: 1.21 to 2.87, P < 0.01. These results indicate that electroacupuncture significantly increases EB penetration across the BBB. Most studies have reported that GFAP, MMP-9, and VEGF were upregulated after treatment. P-gp expression decreased as well. Electroacupuncture can open the BBB, and the sparse-dense wave is currently the most effective electroacupuncture frequency for opening the BBB. VEGF plays an important role in opening the BBB. It is also important to regulate the expression of MMP-9 and GFAP and inhibit the expression of P-gp.
Topics: Rats; Animals; Blood-Brain Barrier; Vascular Endothelial Growth Factor A; Matrix Metalloproteinase 9; Electroacupuncture; Rats, Sprague-Dawley; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily B; Permeability
PubMed: 38536776
DOI: 10.1371/journal.pone.0298533 -
Journal of Diabetes Research 2024Beyond glycemic control, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been proposed to reduce the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Beyond glycemic control, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been proposed to reduce the risk of cardiovascular events. The aim of the present systematic review and meta-analysis is to demonstrate the effects of GLP-1 RA and SGLT2is on intima-media thickness (IMT).
METHODS
PubMed, EMBASE, Web of Science, SCOPUS, and Google Scholar databases were searched from inception to September 9, 2023. All interventional and observational studies that provided data on the effects of GLP-1 RAs or SGLT2is on IMT were included. Critical appraisal was performed using the Joanna Briggs Institute checklists. IMT changes (preintervention and postintervention) were pooled and meta-analyzed using a random-effects model. Subgroup analyses were based on type of medication (GLP-1 RA: liraglutide and exenatide; SGLT2i: empagliflozin, ipragliflozin, tofogliflozin, and dapagliflozin), randomized clinical trials (RCTs), and diabetic patients.
RESULTS
The literature search yielded 708 related articles after duplicates were removed. Eighteen studies examined the effects of GLP-1 RA, and eleven examined the effects of SGLT2i. GLP-1 RA and SGLT2i significantly decreased IMT (MD = -0.123, 95% CI (-0.170, -0.076), < 0.0001, = 98% and MD = -0.048, 95% CI (-0.092, -0.004), = 0.031, = 95%, respectively). Metaregression showed that IMT change correlated with baseline IMT, whereas it did not correlate with gender, duration of diabetes, and duration of treatment.
CONCLUSIONS
Treatment with GLP-1 RA and SGLT2i can lower IMT in diabetic patients, and GLP-1 RA may be more effective than SGLT2i.
Topics: Humans; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide-1 Receptor Agonists; Hypoglycemic Agents; Sodium-Glucose Transporter 2 Inhibitors; Cardiovascular Diseases
PubMed: 38529046
DOI: 10.1155/2024/3212795 -
Cardiovascular Diabetology Mar 2024Randomized controlled trials and real-world studies suggest that combination therapy with sodium-glucose transport protein 2 inhibitors (SGLT2is) and glucagon-like... (Meta-Analysis)
Meta-Analysis
Effectiveness and safety of the combination of sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies.
BACKGROUND
Randomized controlled trials and real-world studies suggest that combination therapy with sodium-glucose transport protein 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is associated with improvement in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), systolic blood pressure (SBP), body mass index (BMI), and total cholesterol levels. However, a systematic review of available real-world evidence may facilitate clinical decision-making in the real-world scenario. This meta-analysis assessed the safety and effectiveness of combinations of SGLT2is + GLP-1RAs with a focus on their cardioprotective effects along with glucose-lowering ability in patients with type 2 diabetes mellitus (T2DM) in a real-world setting.
METHODS
Electronic searches were performed in the PubMed/MEDLINE, PROQuest, Scopus, CINAHL, and Google Scholar databases. Qualitative analyses and meta-analyses were performed using the Joanna Briggs Institute SUMARI software package and Review Manager v5.4, respectively.
RESULTS
The initial database search yielded 1445 articles; of these, 13 were included in this study. The analyses indicated that SGLT2is + GLP-1RAs combinations were associated with significantly lower all-cause mortality when compared with individual therapies (odds ratio [95% confidence interval [CI] 0.49 [0.41, 0.60]; p < 0.00001). Significant reductions in BMI (- 1.71 [- 2.74, - 0.67]; p = 0.001), SBP (- 6.35 [- 10.17, - 2.53]; p = 0.001), HbA1c levels (- 1.48 [- 1.75, - 1.21]; p < 0.00001), and FPG (- 2.27 [- 2.78, - 1.76]; p < 0.00001) were associated with the simultaneous administration of the combination. Changes in total cholesterol levels and differences between simultaneous and sequential combination therapies for this outcome were not significant.
CONCLUSION
This systematic review and meta-analysis based on real-world data suggests that the combination of SGLT2is + GLP-1RAs is associated with lower all-cause mortality and favorable improvements in cardiovascular, renal, and glycemic measurements. The findings drive a call-to-action to incorporate this combination early and simultaneously in managing T2DM patients and achieve potential cardiovascular benefits and renal protection.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Glucagon-Like Peptide-1 Receptor Agonists; Glycated Hemoglobin; Blood Glucose; Cholesterol; Glucagon-Like Peptide-1 Receptor
PubMed: 38500154
DOI: 10.1186/s12933-024-02192-4