Fenofibrate 145mg / Simvastatin 40mg tablets

INTRODUCTION: Macular edema, a major cause of vision loss in diabetic retinopathy, involves retinal fluid accumulation and retinal thickening due to vascular dysfunction and inflammation. Standard treatments include anti-VEGF agents, corticosteroids, and laser photocoagulation, but limitations such as incomplete response and adverse effects exist. Statins, known for lipid-lowering and pleiotropic anti-inflammatory effects, have emerged as a potential therapeutic option. METHODS: We conducted a systematic review and meta-analysis registered with PROSPERO (CRD420251082672) following PRISMA guidelines. Peer-reviewed studies evaluating statins' efficacy and safety in macular edema were identified via multiple databases up to May 2025. Included studies encompassed randomized controlled trials and observational studies involving patients with macular edema treated with statins versus controls. Key outcomes were hard exudate reduction, retinal thickness, visual acuity, diabetic retinopathy progression, and safety. RESULTS: Ten eligible studies involving atorvastatin and simvastatin showed statins significantly reduced hard exudates (risk ratio 4.42, p=0.03) and retinal thickness, with a 58% reduction in diabetic retinopathy progression. Statins also decreased the need for laser treatment by 32%. Visual acuity improvement was inconsistent, with benefits mainly in dyslipidemic patients. Safety analysis revealed no significant increase in adverse events. Statin effects were more pronounced in patients with elevated lipid levels. CONCLUSION: Statins demonstrate promising anatomical and preventive benefits in diabetic macular edema, particularly in patients with dyslipidemia, by reducing lipid exudation and stabilizing retinal vasculature. Despite limited visual acuity improvement, their favorable safety profile supports considering statins as adjunctive therapy. Further large-scale, long-term trials are warranted to confirm these findings and optimize treatment protocols.

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Objective: To systematically assess the clinical effectiveness of combining fenofibrate with statins in treating patients with diabetes mellitus and hyperlipidemia. Methods: Clinical randomized controlled trials assessing the efficacy of fenofibrate and statins in patients with diabetes mellitus and hyperlipidemia were identified from both Chinese and international databases. The experimental group received fenofibrate combined with statins, while the control group received either statins or fenofibrate alone, statins or fenofibrate with placebo, placebo alone, or lifestyle interventions. Results: The analysis incorporated 18 randomized controlled trials with a combined participant count of 2113. The analysis showed that patients in the experimental group had a higher overall efficacy rate than those in the control group (OR = 5.42, 95% CI = 3.11 to 9.45, P < 0. 00001). Furthermore, levels of total cholesterol (SMD = -1.01, 95% CI = -1.60 to -0.41, P = 0.0009), high-density lipoprotein cholesterol (SMD = 1.31, 95% CI = 0.86 to 1.76, P < 0.00001), triglycerides (SMD = -0.94, 95% CI = -1.59 to - 0.30, P = 0. 004), low-density lipoprotein cholesterol (SMD = -2.26, 95% CI = -3.05 to -1.47, P < 0. 00001), fasting plasma glucose (SMD = -0.37, 95% CI = -0.51∼-0.23, P<0. 00001), and postchallenge plasma glucose (SMD =-0.88, 95% CI =-1.19∼-0.57, P<0. 00001) showed significant improvements compared to those in the control group. All of the above differences were statistically significant. Conclusion: This meta-analysis shows that the combination of fenofibrate and statins is superior to statin monotherapy in improving lipid and glycemic profiles (surrogate markers) in patients with diabetes and hyperlipidemia. However, its long-term benefits on cardiovascular hard endpoints need further confirmation, and combination therapy may increase the risk of adverse reactions such as muscular and hepatic events. Clinical application requires balancing benefits and risks, accompanied by enhanced monitoring.

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Lipids disorder is the principal cause of atherosclerosis and may present with several forms, according to blood lipoprotein prevalence. One of the most common forms is combined dyslipidemia, characterized by high levels of triglycerides and low level of high-density lipoprotein. Single lipid-lowering drugs may have very selective effect on lipoproteins; hence, the need to use multiple therapy against dyslipidemia. However, the risk of toxicity is a concerning issue. In this review, the effect and safety of an approved combination therapy with simvastatin plus fenofibrate are described, with an analysis of pros and cons resulting from randomized multicenter trials, meta-analyses, animal models, and case reports as well.

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The combination of statins and fibrates in the treatment of lipid abnormalities effectively regulates individual lipid fraction levels. In this study, the screening and assessment of the physicochemical properties of simvastatin-fenofibrate solid dispersions were performed. Fenofibrate and simvastatin were processed using the kneading method in different weight ratios, and the resulting solid dispersions were assessed using differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), contact angle, as well as dissolution tests. The obtained results confirmed the formation of a simple eutectic phase diagram, with a eutectic point containing 79 wt% fenofibrate and 21 wt% simvastatin, lack of chemical interactions between the ingredients, and simvastatin impact on improving fenofibrate dissolution profile, due to the formation of crystalline solid dispersions by the kneading method.

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The objective of study was to investigate the effects of different doses of simvastatin and fenofibrate on malondialdehyde (MDA) and reduced glutathione (GSH) in the plasma, liver, and brain tissue of male normolipidaemic and hyperlipidaemic rats. Normolipidaemic (Wistar) rats were receiving 10 or 50 mg/kg a day of simvastatin or 30 or 50 mg/kg a day of fenofibrate. Hyperlipidaemic (Zucker) rats were receiving 50 mg/kg/day of simvastatin or 30 mg/kg/day of fenofibrate. Control normolipidaemic and hyperlipidaemic rats were receiving saline. Simvastatin, fenofibrate, and saline were administered by gavage for three weeks. In normolipidaemic rats simvastatin and fenofibrate showed similar and dose-independent effects on plasma and brain MDA and GSH concentrations. Generally, plasma and brain MDA decreased, while brain GSH concentration increased. In hyperlipidaemic rats simvastatin did not affect plasma and brain MDA and GSH concentrations but significantly decreased liver GSH. Fenofibrate decreased plasma and liver MDA but increased brain MDA. In both rat strains fenofibrate significantly decreased liver GSH concentrations, most likely because fenofibrate metabolites bind to GSH. Our findings suggest that simvastatin acts as an antioxidant only in normolipidaemic rats, whereas fenofibrate acts as an antioxidant in both rat strains.

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AIMS: This study investigated the association between fenofibrate use and outcomes of heart failure (HF) in patients with Type 2 diabetes (T2D). METHODS AND RESULTS: In a nationwide cohort database (2008-22) in South Korea, patients with T2D (≥30 years) receiving statin therapy were 1:1 matched by propensity score into a statin plus fenofibrate group (n = 11 722) and statin only group (n = 11 722). The primary outcomes were hospitalization for HF (HHF) and a composite of HHF or cardiovascular death. A Cox proportional hazards model was used to assess the association between treatments and outcomes. During a median of 50.4 months, the incidence rate per 1000 person-years of HHF was 3.44 and 4.13 in the statin plus fenofibrate and statin only groups, respectively (adjusted hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.65-0.98). The adjusted HR for the composite outcome of HHF or cardiovascular death was 0.79 (95% CI, 0.65-0.96). Sensitivity analyses limited to individuals with ≥80% adherence showed consistent results (HHF: adjusted HR, 0.63; 95% CI, 0.43-0.92; composite outcome: adjusted HR, 0.68; 95% CI, 0.48-0.97). CONCLUSION: In this propensity-matched cohort study, the addition of fenofibrate to statins was associated with significantly lower risks of HHF and the composite outcome of HHF or cardiovascular death in patients with T2D, suggesting a novel cardiovascular benefit of fenofibrate.

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Abstract Bone is a complex tissue that fulfills the role of a resistance structure. This quality is most commonly assessed by bone densitometry, but bone strength may not only be related to bone mineral density but also to the preservation of bone cytoarchitectonics. The study included two groups of rats, ovariectomized and non-ovariectomized. Each group was divided into three batches: control, simvastatin-treated, and fenofibrate-treated. In the ovariectomized group, hypolipidemic treatment was instituted at 12 weeks post ovariectomy. One rat from each of the 6 batches was sacrificed 8 weeks after the start of treatment in the group. The experimental study was performed using a Bruker Minispec mq 20 spectrometer operating at a frequency of 20 MHz, subsequently also performed by 1 H T 2 - T 2 molecular exchange maps. The results were represented by T 2 - T 2 molecular exchange maps that showed, comparatively, both pore size and their interconnectivity at the level of the femoral epiphysis, being able to evaluate both the effect of estrogen on bone tissue biology and the effect of the lipid-lowering medication, simvastatin, and fenofibrate, in both the presence and absence of estrogen. T 2 - T 2 molecular exchange maps showed that the absence of estrogen results in an increase in bone tissue pore size and interconnectivity. In the presence of estrogen, lipid-lowering medication, both simvastatin and fenofibrate alter bone tissue cytoarchitectonics by reducing pore interconnectivity. In the absence of estrogen, fenofibrate improves bone tissue cytoarchitectonics, the T 2 - T 2 molecular exchange map being similar to that of non-osteoporotic bone tissue.

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The taste of a drug formulation, especially of orodispersible and liquid dosage forms, is of crucial importance due to its direct contact with the human taste buds. In order to achieve high patient acceptance with these formulations, drugs with an unpleasant, predominantly bitter taste have to be masked. One strategy for masking taste particularly suitable for lipophilic drugs is to dissolve the drug molecules in lipid carrier systems, such as nanoemulsions. Although this strategy has often proven effective as a formulation strategy for improving bioavailability and masking an unpleasant taste, our study indicates that embedding the three poorly water-soluble model drugs fenofibrate, simvastatin, and naproxen in nanoemulsions led to newly created or increased bitterness compared to the non-formulated drug powders. We proved this using both an analytical taste sensor system, specifically an electronic tongue (e-tongue), and a sensory study with a human taste panel. Hereby, complete agreement between the e-tongue measurements and the sensory study was found despite the non-ionic character of fenofibrate and simvastatin. We hypothesize that the changed bitter taste impressions were due to the location of the drug molecules at the oil/water interfaces, which resulted in an increased bitter taste intensity and prolonged duration of the bitter taste. In summary, the study shows that incorporating drugs into lipid nanocarriers tended to worsen the taste rather than mask it.

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