-
PloS One 2024Stroke stands as a significant macrovascular complication among individuals with Type 2 diabetes mellitus (T2DM), often resulting in the primary cause of mortality and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stroke stands as a significant macrovascular complication among individuals with Type 2 diabetes mellitus (T2DM), often resulting in the primary cause of mortality and disability within this patient demographic. Presently, numerous studies have been conducted to investigate the underlying causes of stroke in individuals with T2DM, yet the findings exhibit inconsistencies.
OBJECTIVE
This paper aims to consolidate and summarize the available evidence concerning the influential factors contributing to stroke among patients diagnosed with T2DM.
METHODS
We conducted a comprehensive search across multiple databases, including Cochrane Library, PubMed, Web Of Science, Embase, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wanfang and Weipu up to August 2023. Google Scholar was also searched to retrieve gray literature. We calculated odds ratios (OR) and 95% confidence intervals (CI) using Stata software.
RESULTS
Our analysis encompassed 43 observational studies, exploring factors across sociodemographic, biochemical, complications, and hypoglycemic agent categories. The findings identified several risk factors for stroke in patients with T2DM: age, gender, T2DM duration, hypertension, body-mass index (BMI), smoking, Glycated hemoglobin (HbA1c), estimated Glomerular Filtration Rate (eGFR), albuminuria, Triglycerides (TG), Low density lipoprotein cholesterol (LDL-C), Coronary heart disease (CHD), Atrial fibrillation (AF), diabetic retinopathy (DR), Peripheral vascular disease (PVD), and carotid plaque. Conversely, exercise, High density lipoprotein cholesterol (HDL-C), metformin (MET), pioglitazone, and metformin combination therapy emerged as protective factors.
CONCLUSION
This study underscores the multitude of influencing factors contributing to stroke in people with T2DM patients, among which the microvascular complications of T2DM play an most important role. Therefore, we emphasize the importance of screening for microvascular complications in patients with T2DM. However, due to limitations arising from the number of articles reviewed, there remain areas where clarity is lacking. Further research efforts are warranted to expand upon and reinforce our current findings.
Topics: Diabetes Mellitus, Type 2; Humans; Stroke; Risk Factors; Hypoglycemic Agents; Glycated Hemoglobin
PubMed: 38913694
DOI: 10.1371/journal.pone.0305954 -
Frontiers in Endocrinology 2024The progression of carotid intima-media thickness (cIMT) can partially predict the occurrence of future cardiovascular events. This network meta-analysis compared the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The progression of carotid intima-media thickness (cIMT) can partially predict the occurrence of future cardiovascular events. This network meta-analysis compared the effects of 14 antidiabetic drugs (acarbose, alogliptin, exenatide, glibenclamide, glimepiride, ipragliflozin, metformin, nateglinide, pioglitazone, rosiglitazone, sitagliptin, tofoglifozin, troglitazone, voglibose) on the progression of cIMT.
METHOD
PubMed, EMBASE, Cochrane Library, and Web of Science were searched to screen all clinical trials of treatment of cIMT with hypoglycemic agents before March 1, 2024. The differences in the changes in cIMT between the treatment group and control group were evaluated.
RESULT
After screening 8395 citations, 25 studies (6675 patients) were included. The results indicated that exenatide had the best efficacy in slowing down cIMT progress, and exenatide [MD=-0.13,95%CI (-0.25, -0.01)], alogliptin [MD=-0.08,95%CI (-0.13, -0.02)] and metformin [MD=-0.05, 95%CI (-0.09, -0.02)] are more effective than placebo.
CONCLUSION
Long-term treatment of exenatide, alogliptin, and metformin may be more effective than other hypoglycemic drugs in slowing the progression of cIMT.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024519474.
Topics: Humans; Hypoglycemic Agents; Carotid Intima-Media Thickness; Network Meta-Analysis; Disease Progression; Diabetes Mellitus, Type 2
PubMed: 38883606
DOI: 10.3389/fendo.2024.1403606 -
Progress in Neuro-psychopharmacology &... Jun 2024The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic... (Review)
Review
BACKGROUND
The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD.
METHODS
PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected.
RESULTS
Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1β, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients.
CONCLUSION
Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.
PubMed: 38879067
DOI: 10.1016/j.pnpbp.2024.111056 -
Medicine and Pharmacy Reports Jan 2024Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, with an increasing prevalence in all regions of the world. Its spectrum includes... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, with an increasing prevalence in all regions of the world. Its spectrum includes hepatic steatosis (HS) and non-alcoholic steatohepatitis (NASH) with progression to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). NAFLD may represent the hepatic manifestation of the metabolic syndrome (MS), with a prevalence directly proportional to the prevalence of obesity and MS. The standard treatment for patients with NAFLD is lifestyle modification, which in medical practice has many limitations. To overcome them, numerous drugs with benefits in the prevention and treatment of the disease have been studied. Currently, the most used substances are vitamin E and Pioglitazone, with numerous benefits. Furthermore, new strategies and beneficial treatments are needed for the prevention of the disease, which is currently a priority in both the health and research fields. One of the most studied agents in the last decades has been ursodeoxycholic acid (UDCA), which is of great interest in the treatment of NAFLD due to its hepatoprotective effects.
PubMed: 38344336
DOI: 10.15386/mpr-2629 -
Neurology India 2023Disease-modifying agents like Pioglitazone have shown promising effects on neuroinflammation and homeostasis of amyloid plaques, but there is a lack of research papers... (Meta-Analysis)
Meta-Analysis Review
Drug Repositioning of Pioglitazone in Management and Improving the Cognitive Function among the Patients With Mild to Moderate Alzheimer's Disease: A Systematic Review and Meta-Analysis.
BACKGROUND
Disease-modifying agents like Pioglitazone have shown promising effects on neuroinflammation and homeostasis of amyloid plaques, but there is a lack of research papers providing conclusive evidence.
OBJECTIVES
This study is aimed to determine the safety and efficacy of Pioglitazone in improving cognitive function in patients with mild-moderate Alzheimer's disease (AD).
MATERIALS AND METHODS
Trials published in the last 12 years were identified from PubMed, Scopus, Cochrane Central, and other trial registries. Five hundred twenty-five records were obtained, from which five studies were included for quantitative analysis. Studies comparing Pioglitazone with a suitable placebo or other oral hypoglycemic agent were considered for review. Data was extracted using a pretested form, which was followed by a risk of bias assessment (ROB) with Cochrane's ROB assessment tool.
RESULTS
This meta-analysis included studies where Pioglitazone (15-30 mg) was compared to other oral hypoglycemic agents, placebo, or diabetic diet for a minimum duration of 6 months. Pioglitazone did not show a statistically significant improvement in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores [mean difference (MD): -1.16; 95% confidence interval (CI): -4.14-1.81]. By conducting sensitivity analysis with the removal of one study, significant efficacy was obtained [MD: -2.75; 95% CI: -4.84--0.66]. The Wechsler Memory Scale-Revised logical memory I (WMS-R) scores had a significant improvement in the Pioglitazone group [MD: 2.02; 95% CI: 0.09-3.95].
CONCLUSION
Pioglitazone is a safe medication that has a promising effect in slowing the advancement of AD.
Topics: Humans; Alzheimer Disease; Pioglitazone; Drug Repositioning; Cognition
PubMed: 38174446
DOI: 10.4103/0028-3886.391397 -
BMC Medicine Nov 2023Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely related and mutually contribute to the disease's development. There are many... (Meta-Analysis)
Meta-Analysis
Comparative effectiveness of multiple different treatment regimens for nonalcoholic fatty liver disease with type 2 diabetes mellitus: a systematic review and Bayesian network meta-analysis of randomised controlled trials.
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely related and mutually contribute to the disease's development. There are many treatment options available to patients. We provide a comprehensive overview of the evidence on the treatment effects of several potential interventions for NAFLD with T2DM.
METHODS
This systematic review and network meta-analysis included searches of PubMed, Embase, Cochrane Library, and Web of Science from inception to June 30, 2023, for randomised controlled trials of treatment of NAFLD with T2DM. We performed Bayesian network meta-analyses to summarise effect estimates of comparisons between interventions. We applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) frameworks to rate all comparative outcomes' certainty in effect estimates, categorise interventions, and present the findings. This study was registered with PROSPERO, CRD42022342373.
RESULTS
Four thousand three hundred and sixty-nine records were retrieved from the database and other methods, of which 24 records were eligible for studies enrolling 1589 participants. Eight clinical indicators and 14 interventions were finally in focus. Referring to the lower surface under the cumulative ranking curves (SUCRA) and the league matrix table, exenatide and liraglutide, which are also glucagon-like peptide-1 receptor agonists (GLP-1RAs), showed excellent potential to reduce liver fat content, control glycemia, reduce body weight, and improve liver function and insulin resistance. Exenatide was more effective in reducing glycated haemoglobin (HbA) (mean difference (MD) 0.32, 95%CI 0.12 to 0.52), lowering BMI (MD 0.81, 95%CI 0.18 to 1.45), and lowering alanine transaminase (ALT) (MD 10.96, 95%CI 5.27 to 16.66) compared to liraglutide. However, this evidence was assessed as low certainty. Omega-3 was the only intervention that did not have a tendency to lower HbA, with standard-treatment (STA-TRE) as reference (MD - 0.17, 95%CI - 0.42 to 0.07). Glimepiride is the only intervention that causes an increase in ALT levels, with standard-treatment (STA-TRE) as reference (MD - 11.72, 95%CI - 17.82 to - 5.57). Based on the available evidence, the treatment effects of pioglitazone, dapagliflozin, and liraglutide have a high degree of confidence.
CONCLUSIONS
The high confidence mandates the confident application of these findings as guides for clinical practice. Dapagliflozin and pioglitazone are used for glycaemic control in patients with NAFLD combined with T2DM, and liraglutide is used for weight loss therapy in patients with abdominal obesity. The available evidence does not demonstrate the credibility of the effectiveness of other interventions in reducing liver fat content, visceral fat area, ALT, and insulin resistance. Future studies should focus on the clinical application of GLP-1Ras and the long-term prognosis of patients.
Topics: Humans; Diabetes Mellitus, Type 2; Exenatide; Hypoglycemic Agents; Liraglutide; Non-alcoholic Fatty Liver Disease; Network Meta-Analysis; Pioglitazone; Insulin Resistance; Bayes Theorem
PubMed: 37974258
DOI: 10.1186/s12916-023-03129-6 -
Cureus Oct 2023Modern diabetic treatment has gone beyond glycemic control, with the choice of different medications to attain therapeutic targets also affected by the risk of long-term... (Review)
Review
Modern diabetic treatment has gone beyond glycemic control, with the choice of different medications to attain therapeutic targets also affected by the risk of long-term outcomes and safety profiles. The effect of diabetes on increased morbidity and mortality and its relationship to cardiovascular outcomes and coronary artery diseases have driven recent diabetes studies toward medications that improve cardiovascular outcomes and reduce all-cause mortality. This is attained by holistically treating cardiovascular complications in type 2 diabetic patients beyond glycemic control. Moreover, both diabetes and pre-diabetes are considered risk factors for both microvascular and macrovascular cardiac events. Despite the fact that initial research acknowledged fluid retention as a safety issue in pioglitazone use, clinical trial data have not presented conclusive proof of a positive or negative impact on cardiac function. This comprehensive literature review aims to evaluate the effect of pioglitazone on all-cause mortality, hospitalizations for heart failure, and major adverse cardiovascular outcomes, including the individual outcomes of non-fatal stroke, non-fatal myocardial infarction, and cardiovascular mortality.
PubMed: 37954768
DOI: 10.7759/cureus.46911 -
European Neuropsychopharmacology : the... Jan 2024Growing evidence suggests an association between inflammatory processes and depressive disorders (DD). DD typically emerge during adolescence. Treatment effects of... (Meta-Analysis)
Meta-Analysis Review
Growing evidence suggests an association between inflammatory processes and depressive disorders (DD). DD typically emerge during adolescence. Treatment effects of agents with anti-inflammatory properties in youth DD have not been systematically reviewed. Here, the existing evidence on the use of anti-inflammatory drugs (including polyunsaturated fatty acids, nonsteroidal anti-inflammatory drugs, cytokine inhibitors, statins, pioglitazone, corticosteroids, and minocycline or modafinil) in children and adolescents with DD was synthesized using meta-analysis. The PROSPERO preregistered search yielded 22 records meeting search criteria. Of these, data from 19 primary studies (n = 1366 subjects) were subjected to meta-analysis. A significant but small effect in favor of anti-inflammatory agents in reducing depressive symptoms in youth with DD was found (SMD = -0.29, 95 % CI = -0.514; -0.063, p = 0.01). Post-hoc analyzes of drug subclasses found a significant effect of omega-3 fatty acids in reducing depressive symptoms. Results underline the importance to consider inflammatory pathways in the supplemental treatment of youth with DD. Further research is warranted, to clarify if anti-inflammatory agents are only effective in a subpopulation of patients (inflammatory biotype of depression in youth) and/or to alleviate specific symptom domains of depression (e.g., cognitive symptoms).
Topics: Child; Humans; Adolescent; Depression; Anti-Inflammatory Agents; Minocycline; Pioglitazone; Fatty Acids, Omega-3
PubMed: 37864981
DOI: 10.1016/j.euroneuro.2023.09.006 -
Hormones (Athens, Greece) Dec 2023To assess the comparative efficacy of glucose-lowering drugs on liver steatosis as assessed by means of magnetic resonance imaging (MRI) in patients with T2D. (Meta-Analysis)
Meta-Analysis
Comparative efficacy of glucose-lowering drugs on liver steatosis as assessed by means of magnetic resonance imaging in patients with type 2 diabetes mellitus: systematic review and network meta-analysis.
PURPOSE
To assess the comparative efficacy of glucose-lowering drugs on liver steatosis as assessed by means of magnetic resonance imaging (MRI) in patients with T2D.
METHODS
We searched several databases and grey literature sources. Eligible trials had at least 12 weeks of intervention, included patients with T2D, and assessed the efficacy of glucose-lowering drugs as monotherapies. The primary outcome of interest was absolute reduction in liver fat content (LFC), assessed by means of MRI. Secondary efficacy outcomes were reduction in visceral and subcutaneous adipose tissue. We performed random effects frequentist network meta-analyses to estimate mean differences (MDs) with 95% confidence intervals (CIs). We ranked treatments based on P-scores.
RESULTS
We included 29 trials with 1906 patients. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (P-score 0.84) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (0.71) were the most efficacious in terms of liver fat content reduction. Among individual agents, empagliflozin was the most efficacious (0.86) and superior to pioglitazone (MD -5.7, 95% CI -11.2 to -0.3) (very low confidence). GLP-1 RAs had also the most favorable effects on visceral and subcutaneous adipose tissue.
CONCLUSIONS
GLP-1 RAs and SGLT-2 inhibitors seem to be the most efficacious glucose-lowering drugs for liver steatosis in patients with T2D. Assessment of their efficacy on NAFLD in patients irrespective of presence of T2D is encouraged.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Network Meta-Analysis; Glucose; Non-alcoholic Fatty Liver Disease; Glucagon-Like Peptide 1
PubMed: 37770761
DOI: 10.1007/s42000-023-00493-z -
Cureus Sep 2023Non-alcoholic fatty liver disease (NAFLD) is a complication related to obesity and metabolic syndrome. There are increased incidences of NAFLD/non-alcoholic... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is a complication related to obesity and metabolic syndrome. There are increased incidences of NAFLD/non-alcoholic steatohepatitis (NASH) due to rising obesity and type 2 diabetes mellitus (T2DM). This has resulted in significant morbidity and mortality. The two promising therapeutic agents for treating NAFLD/NASH are sodium-glucose cotransporter 2 (SGLT2) inhibitors and pioglitazone. The reason is their potential to target underlying pathophysiological mechanisms. SGLT2 inhibitors may help treat NAFLD/NASH by reducing insulin resistance and improving glucose control, thereby lowering hepatic fat accumulation and inflammation, although their exact mechanism in this context is still being studied. This systematic review aims to compare the efficacy of SGLT2 inhibitors and pioglitazone in treating NAFLD/NASH. Major research literature databases were searched, and appropriate keywords were used to find relevant articles published in the last three years. Eighteen studies were critically evaluated using standardized quality assessment tools. Among those, nine studies qualified as medium or high quality and were included in the review. Both SGLT2 inhibitors and pioglitazone showed promising results in improving NAFLD/NASH. The efficacy outcomes assessed liver fat content, liver enzyme levels, histological improvement, and metabolic parameters. The safety outcomes considered adverse events and cardiovascular events. The conducted review suggests that SGLT2 inhibitors and pioglitazone are potential treatment options for NAFLD/NASH. Having said that, individualized considerations are essential. It includes patient comorbidities, preferences, and overall safety profiles. Further research is needed to assess long-term effects and outcomes. It would provide more definitive evidence of these treatment options' comparative efficacy and safety for NAFLD/NASH.
PubMed: 37745748
DOI: 10.7759/cureus.45789