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Parkinson's Disease 2019In the early sixties, a discussion started regarding the association between Parkinson's disease (PD) and type II diabetes mellitus (T2DM). Today, this potential... (Review)
Review
In the early sixties, a discussion started regarding the association between Parkinson's disease (PD) and type II diabetes mellitus (T2DM). Today, this potential relationship is still a matter of debate. This review aims to analyze both diseases concerning causal relationships and treatments. A total of 104 articles were found, and studies on animal and "in vitro" models showed that T2DM causes neurological alterations that may be associated with PD, such as deregulation of the dopaminergic system, a decrease in the expression of peroxisome proliferator-activated receptor-gamma coactivator-1 (), an increase in the expression of phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes 15 (PED/PEA-15), and neuroinflammation, as well as acceleration of the formation of alpha-synuclein amyloid fibrils. In addition, clinical studies described that Parkinson's symptoms were notably worse after the onset of T2DM, and seven deregulated genes were identified in the DNA of T2DM and PD patients. Regarding treatment, the action of antidiabetic drugs, especially incretin mimetic agents, seems to confer certain degree of neuroprotection to PD patients. In conclusion, the available evidence on the interaction between T2DM and PD justifies more robust clinical trials exploring this interaction especially the clinical management of patients with both conditions.
PubMed: 31871617
DOI: 10.1155/2019/4951379 -
Systematic Reviews Jan 2024Up to 40% of UDCA-treated patients do not have an adequate clinical response. Farnesoid X receptor agonists, peroxisome proliferator-activated receptor agonists, and... (Meta-Analysis)
Meta-Analysis
Optimal drug regimens for improving ALP biochemical levels in patients with primary biliary cholangitis refractory to UDCA: a systematic review and Bayesian network meta-analysis.
BACKGROUND
Up to 40% of UDCA-treated patients do not have an adequate clinical response. Farnesoid X receptor agonists, peroxisome proliferator-activated receptor agonists, and fibroblast growth factor 19 analogs were developed as adjunctive therapy. The aim of this network meta-analysis was to compare the efficacy of these drugs as add-on therapy for patients with primary biliary cholangitis (PBC) refractory to UDCA in improving ALP levels.
METHODS
We searched PubMed, Embase, Web of Science, and the Cochrane Library for eligible studies until 1 December 2023. Randomized controlled trials, cohort studies, and case-control studies comparing the efficacy of different combination treatments and UDCA monotherapy in UDCA-refractory PBC patients were included in the analysis. Cumulative probability was used to rank the included treatments.
RESULTS
A total of 23 articles were eligible for our network meta-analysis. In terms of improving ALP levels, In terms of improving ALP biochemical levels, bezafibrate combined with UDCA (MD 104.49, 95% CI 60.41, 161.92), fenofibrate combined with UDCA (MD 87.81, 95% CI (52.34, 129.79), OCA combined with UDCA (MD 65.21, 95% CI 8.99, 121.80), seladelpar combined with UDCA (MD 117.39, 95% CI 19.97, 213.95), elafibranor combined with UDCA (MD 140.73, 95% CI 74.34, 209.98), saroglitazar combined with UDCA (MD 132.09, 95% CI 13.99, 247.04) was more effective than UDCA monotherapy. Elafibranor in combination with UDCA was the most likely (32%) to be the optimal drug regimen.
CONCLUSION
As second-line therapy for UDCA-refractory PBC, PPAR agonists were more effective than any other drugs with other mechanisms in improving ALP biochemical levels, with elafibranor being the best.
Topics: Humans; Liver Cirrhosis, Biliary; Ursodeoxycholic Acid; Bayes Theorem; Network Meta-Analysis; Drug Therapy, Combination; Treatment Outcome; Randomized Controlled Trials as Topic; Propionates; Chalcones
PubMed: 38287391
DOI: 10.1186/s13643-024-02460-0 -
International Journal of Molecular... Apr 2024Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver conditions, and its progression is marked by evolution to non-alcoholic steatosis,... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver conditions, and its progression is marked by evolution to non-alcoholic steatosis, steatohepatitis, cirrhosis related to non-alcoholic steatohepatitis, and the potential occurrence of hepatocellular carcinoma. In our systematic review, we searched two databases, Medline (via Pubmed Central) and Scopus, from inception to 5 February 2024, and included 73 types of research (nine clinical studies and 64 pre-clinical studies) from 2854 published papers. Our extensive research highlights the impact of Berberine on NAFLD pathophysiology mechanisms, such as Adenosine Monophosphate-Activated Protein Kinase (AMPK), gut dysbiosis, peroxisome proliferator-activated receptor (PPAR), Sirtuins, and inflammasome. Studies involving human subjects showed a measurable reduction of liver fat in addition to improved profiles of serum lipids and hepatic enzymes. While current drugs for NAFLD treatment are either scarce or still in development or launch phases, Berberine presents a promising profile. However, improvements in its formulation are necessary to enhance the bioavailability of this natural substance.
Topics: Berberine; Non-alcoholic Fatty Liver Disease; Humans; Animals; Liver Cirrhosis; Liver
PubMed: 38673787
DOI: 10.3390/ijms25084201 -
Journal of Gastrointestinal Surgery :... Feb 2022The peroxisome proliferator-activated receptor (PPAR)-γ plays a key role in adipose tissue differentiation and fat metabolism. However, it is unclear which factors may...
BACKGROUND
The peroxisome proliferator-activated receptor (PPAR)-γ plays a key role in adipose tissue differentiation and fat metabolism. However, it is unclear which factors may regulate its expression and whether obese patients have changes in adipose tissue expression of PPAR-γor potential regulators such as miR-27. Thus, our aims were to analyze PPAR-γ and miR-27 expression in adipose tissue of obese patients, and to correlate their levels with clinical variables.
SUBJECTS AND METHODS
We included 43 morbidly obese subjects who underwent sleeve gastrectomy (31 of them completed 1-year follow-up) and 19 non-obese subjects. mRNA expression of PPAR-γ1 and PPAR-γ2, miR-27a, and miR-27b was measured by qPCR in visceral and subcutaneous adipose tissue. Clinical variables and serum adipokine and hormone levels were correlated with PPAR-γ and miR-27 expression. In addition, a systematic review of the literature regarding PPAR-γ expression in adipose tissue of obese patients was performed.
RESULTS
We found no differences in the expression of PPAR-γ and miR-27 in adipose tissue of obese patients vs. controls. The literature review revealed discrepant results regarding PPAR-γ expression in adipose tissue of obese patients. Of note, we described a significant negative correlation between pre-operative PPAR-γ1 expression in adipose tissue of obese patients and post-operative weight loss, potentially linked with insulin resistance markers.
CONCLUSION
PPAR-γ1 expression in adipose tissue is associated with weight loss after sleeve gastrectomy and may be used as a biomarker for response to surgery.
Topics: Adipose Tissue; Gastrectomy; Gene Expression; Humans; MicroRNAs; Obesity, Morbid; PPAR gamma; Peroxisome Proliferator-Activated Receptors; Weight Loss
PubMed: 34882294
DOI: 10.1007/s11605-021-05216-6 -
Frontiers in Physiology 2022Blood flow restriction (BFR) exercise may be a potential exercise program to promote angiogenesis. This review aims to compare the effects of exercise with and without...
BACKGROUND
Blood flow restriction (BFR) exercise may be a potential exercise program to promote angiogenesis. This review aims to compare the effects of exercise with and without BFR on angiogenesis-related factors in skeletal muscle among healthy adults.
METHODOLOGY
Searches were made in Web of Science, Scopus, PubMed, and EBSCO databases from January 2001 to June 2021. Studies were screened, quality was evaluated, and data were extracted. The review protocol was registered at PROSPERO (PROSPERO registration number: CRD42021261367). Standardized mean differences (SMD) of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR-2), hypoxia inducible factor 1α (HIF-1α), peroxisome proliferator-activated receptorγcoactivator-1α (PGC-1α) and endothelial nitric oxide synthase (eNOS) were analyzed using Revman 5.4 software with a 95% confidence interval (95% CI).
RESULTS
Ten studies fulfilled the inclusion criteria with a total of 75 participants for BFR group and 77 for CON group. BFR exercise elicits greater expression of VEGF (heterogeneity test, = 0.09, I = 44%; SMD, 0.93 [0.38, 1.48], < 0.05), VEGFR-2 (heterogeneity test, = 0.81, I = 0%; SMD, 0.64 [0.08, 1.21], < 0.05), HIF-1α (heterogeneity test, = 0.67, I = 0%; SMD, 0.43 [0.03, 0.82], < 0.05), PGC-1α (heterogeneity test, = 0.02, I = 54%; SMD, 0.74 [0.21, 1.28], < 0.05) and eNOS (heterogeneity test, = 0.88, I = 0%; SMD, 0.60 [0.04, 1.17], < 0.05) mRNA than non-BFR exercise. In the sub-group analysis, resistance exercise with BFR elicits greater expression of VEGF (heterogeneity test, = 0.36, I = 6%; SMD, 1.66 [0.97, 2.35], < 0.05) and HIF-1α (heterogeneity test, = 0.56, I = 0%; SMD, 0.51 [0.01, 1.02], < 0.05) mRNA than aerobic exercise with BFR.
CONCLUSION
Exercise with BFR elicited more angiogenesis-related factors mRNA expression than exercise without BFR, but not VEGF and PGC-1α protein expression. Therefore, BFR training may be a potential training program to improve vascular function.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021261367].
PubMed: 35250618
DOI: 10.3389/fphys.2022.814965 -
Oxidative Medicine and Cellular... 2021() and its ingredients (IFP) have a variety of biological activities and are widely used to treat osteoporosis (OP). Herein, we conducted a systematic review to... (Meta-Analysis)
Meta-Analysis
Antiosteoporosis Effect and Possible Mechanisms of the Ingredients of Fructus Psoraleae in Animal Models of Osteoporosis: A Preclinical Systematic Review and Meta-Analysis.
OBJECTIVE
() and its ingredients (IFP) have a variety of biological activities and are widely used to treat osteoporosis (OP). Herein, we conducted a systematic review to evaluate the efficacy of IFP for an animal model of OP from the current literatures. Potential mechanisms of IFP in the treatment of OP were also summarized.
MATERIALS AND METHODS
We carried out a search for electronic literature in the PubMed, Chinese National Knowledge Infrastructure, EMBASE, Wanfang, Web of Science, Chinese Biomedical Literature Database, and Cochrane Library, as well as Chinese VIP databases targeting articles published from inception to June 2021. The inclusion criteria were animal studies that assessed the efficacy and safety of IFP for OP, regardless of publication status or language. The exclusion criteria included (1) other types of studies (in vitro studies, case reports, clinical trials, reviews, abstracts, comments, and editorials), (2) combination with other compounds, (3) compared with other traditional Chinese medicine, (4) not osteoporosis or bone loss model, (5) studies with insufficient data, (6) lack of a control group, and (7) duplicate publications. The modified Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Stroke (CAMARADES) 10-item quality checklist was used to evaluate the risk of bias of included studies. We computed the relative risk (RR) and the standard mean difference (SMD) for dichotomous outcomes and continuous outcomes, respectively. When heterogeneity was detected or there was significant statistical heterogeneity ( < 0.05 or > 50%), a random-effects model was employed, followed by further subgroup analysis and metaregression estimations to ascertain the origins of heterogeneity. Otherwise, we used a fixed-effects model ( ≥ 0.05 or ≤ 50%). The primary outcome measures were bone mineral density (BMD), serum osteocalcin(S-OCN), bone volume over total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), bone maximum load, and elasticity modulus. The secondary outcome measure was the antiosteoporosis mechanisms of IFP. The STATA 12.0 software was used to analyze the data.
RESULTS
Overall, 16 studies focusing on 379 animals were enrolled into the study. The risk of bias score of included studies ranged from 4 to 7 with an average score of 5.25. The present study provided the preliminary preclinical evidence that administration of IFP could significantly increase the S-OCN, BMD, BV/TV, and Tb.N while Tb.Th and Tb.Sp were remarkably decreased by IFP in OP model animals ( < 0.05). Moreover, IFP could significantly improve the bone biomechanical indicator bone maximum load and elasticity modulus ( < 0.05). In terms of the possible mechanisms of treatment of OP, IFP exerts anti-OP effects in animal models probably through osteoprotegerin/receptor activator of the nuclear factor-B ligand/receptor activator of nuclear factor-B (OPG/RANKL/RANK), peroxisome proliferator activated receptor (PPAR-)/Axin2/Wnt, antioxidative stress via forkhead box O3a (FoxO3a)/Axin2/Wnt, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), estrogen-like effect, and gamma-aminobutyric acid/gamma-aminobutyric acid receptor (GABA/GABARI) signaling pathway.
CONCLUSION
Taken together, the findings suggest the possibility of developing IFP as a drug or an ingredient in diet for the clinical treatment of OP. We recommend that rigorous, as well as high-quality, trials involving large sample sizes should be conducted to confirm our findings.
Topics: Animals; Fruit; Medicine, Chinese Traditional; Osteoporosis
PubMed: 34868453
DOI: 10.1155/2021/2098820 -
Cureus Dec 2023This systematic review evaluates the effects of the daily intake of rosehip extract on low-density lipoprotein cholesterol (LDL-C) and blood glucose levels. It... (Review)
Review
This systematic review evaluates the effects of the daily intake of rosehip extract on low-density lipoprotein cholesterol (LDL-C) and blood glucose levels. It synthesizes findings from randomized clinical trials focusing on cardiovascular and metabolic health outcomes. The review includes studies employing various forms of rosehip supplementation, assessing primary outcomes such as LDL-C, HDL-C, total cholesterol, triglycerides, fasting blood glucose (FBG), and glycated hemoglobin (HbA1c). Secondary outcomes, such as body weight, BMI, and blood pressure, are also considered. The paper discusses the potential mechanisms of rosehip's action, including modulation of peroxisome proliferator-activated receptors and effects on various metabolic pathways. The results indicate mixed effects on lipid profiles and blood glucose levels, with some studies showing significant benefits. This review underscores the need for further research to confirm optimal dosages, treatment durations, and rosehip's efficacy in diverse populations, considering its favorable safety profile. The findings suggest the potential of rosehip extract as a complementary agent in managing cardiometabolic risk factors.
PubMed: 38283449
DOI: 10.7759/cureus.51225 -
The Cochrane Database of Systematic... Jan 2023Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering... (Review)
Review
BACKGROUND
Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. This is an update of a review first published in January 2014 and subsequently updated in December 2017 and October 2019.
OBJECTIVES
To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA).
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (1 January 2022), the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 12), MEDLINE (1949 to 1 January 2022), Embase (1980 to 1 January 2022), CINAHL (1982 to 1 January 2022), AMED (1985 to 1 January 2022), and 11 Chinese databases (1 January 2022). In an effort to identify further published, unpublished, and ongoing trials, we searched ongoing trials registers, reference lists, and relevant conference proceedings, and contacted authors and pharmaceutical companies. We did not impose any language restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) evaluating PPAR-γ agonists versus placebo for the secondary prevention of stroke and related vascular events in people with stroke or TIA, with the outcomes of recurrent stroke, vascular events, and adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy, and assessed methodological quality and risk of bias. We evaluated the certainty of evidence for each outcome using the GRADE approach.
MAIN RESULTS
We identified five RCTs with 5039 participants; two studies had a low risk of bias for all domains. Four studies evaluated the drug pioglitazone, and one study evaluated rosiglitazone. The participants in different studies were heterogeneous. Recurrent stroke Three studies evaluated the number of participants with recurrent stroke (4979 participants, a single study contributing 3876 of these). Peroxisome proliferator-activated receptor gamma agonists probably reduce the recurrence of stroke compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.44 to 0.99; moderate-certainty evidence). Adverse events Evidence that adverse events occurred more frequently in participants treated with PPAR-γ agonists when compared with placebo was uncertain due to wide confidence intervals and high levels of statistical heterogeneity: risk difference 10%, 95% CI -8% to 28%; low-certainty evidence). Data were available on additional composite outcomes reflecting serious vascular events (all-cause death and other major vascular events; all-cause mortality, non-fatal myocardial infarction or non-fatal stroke) from one study in 984 people. This study provided low-certainty evidence that PPAR-γ agonists led to fewer events (data not meta-analysed). Vascular events Peroxisome proliferator-activated receptor gamma agonists given over a mean duration of 34.5 months in a single trial of 984 participants may reduce serious vascular events expressed as a composite outcome of total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (RR 0.73, 95% CI 0.54 to 0.99; low-certainty evidence). Other outcomes One study in 20 people measured insulin sensitivity, and one study in 40 people measured the ubiquitin-proteasome activity in carotid plaques. Our confidence in the improvements observed with PPAR-γ agonists were limited by small sample sizes and risk of bias. None of the studies reported the number of participants with disability due to vascular events or improvement in quality of life.
AUTHORS' CONCLUSIONS
Peroxisome proliferator-activated receptor gamma agonists probably reduce recurrent stroke and total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, and may improve insulin sensitivity and the stabilisation of carotid plaques. Their effects on adverse events are uncertain. Our conclusions should be interpreted with caution considering the small number and the quality of the included studies. Further well-designed, double-blind RCTs with large samples are required to assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events in people with stroke or TIA.
Topics: Humans; Ischemic Attack, Transient; PPAR gamma; Insulin Resistance; Stroke; Myocardial Infarction; Randomized Controlled Trials as Topic
PubMed: 36625492
DOI: 10.1002/14651858.CD010693.pub6 -
The Cochrane Database of Systematic... Oct 2019Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering... (Review)
Review
BACKGROUND
Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. This is an update of a review first published in January 2014 and subsequently updated in December 2017.
OBJECTIVES
To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA).
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (30 July 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 7), MEDLINE (1949 to 30 July 2019), Embase (1980 to 30 July 2019), CINAHL (1982 to 30 July 2019), AMED (1985 to 30 July 2019), and 11 Chinese databases (30 July 2019). In an effort to identify further published, unpublished, and ongoing trials, we searched ongoing trials registers, reference lists, and relevant conference proceedings, and contacted authors and pharmaceutical companies. We did not impose any language restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) evaluating PPAR-γ agonists versus placebo for the secondary prevention of stroke and related vascular events in people with stroke or TIA, with the outcomes of recurrent stroke, vascular events, and adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy, and assessed methodological quality and risk of bias. We evaluated the quality of evidence for each outcome using the GRADE approach.
MAIN RESULTS
We identified five RCTs with 5039 participants; two studies had a low risk of bias for all domains. Four studies evaluated the drug pioglitazone, and one study evaluated rosiglitazone. The participants in different studies were heterogeneous.Recurrent strokeThree studies evaluated the number of participants with recurrent stroke (4979 participants, a single study contributing 3876 of these). Peroxisome proliferator-activated receptor gamma agonists probably reduce the recurrence of stroke compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.44 to 0.99; moderate-quality evidence).Adverse eventsEvidence that adverse events occurred more frequently in participants treated with PPAR-γ agonists when compared with placebo was uncertain due to wide confidence interval and high levels of statistical heterogeneity: risk difference 10%, 95% CI -8% to 28%; low-quality evidence).Data were available on additional composite outcomes reflecting serious vascular events (all-cause death and other major vascular events; all-cause mortality, non-fatal myocardial infarction or non-fatal stroke) from one study in 984 people. This study provided low-quality evidence that PPAR-γ agonists led to fewer events (data not meta-analysed).Vascular eventsPeroxisome proliferator-activated receptor gamma agonists given over a mean duration of 34.5 months in a single trial of 984 participants may reduce serious vascular events expressed as a composite outcome of total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (RR 0.73, 95% CI 0.54 to 0.99; low-quality evidence).Other outcomesOne study in 20 people measured insulin sensitivity, and one study in 40 people measured the ubiquitin-proteasome activity in carotid plaques. Our confidence in the improvements observed with PPAR-γ agonists were limited by small sample sizes and risk of bias. None of the studies reported the number of participants with disability due to vascular events or improvement in quality of life.
AUTHORS' CONCLUSIONS
Peroxisome proliferator-activated receptor gamma agonists probably reduce recurrent stroke and total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, and may improve insulin sensitivity and the stabilisation of carotid plaques. Their effects on adverse events are uncertain. Our conclusions should be interpreted with caution considering the small number and the quality of the included studies. Further well-designed, double-blind RCTs with large samples are required to assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events in people with stroke or TIA.
PubMed: 31596946
DOI: 10.1002/14651858.CD010693.pub5 -
Scientific Reports Apr 2024The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through... (Meta-Analysis)
Meta-Analysis
The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.
Topics: Humans; Metformin; Peroxisome Proliferator-Activated Receptors; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Drug Therapy, Combination
PubMed: 38627464
DOI: 10.1038/s41598-024-59390-z