Development and clinical application of bioelectrical impedance analysis method for body composition assessment.

Obesity, which is characterized by excessive body fat, increases the risk of chronic diseases, such as type 2 diabetes, cardiovascular diseases, and certain cancers. Sarcopenia, a decline in muscle mass, is also associated with many chronic disorders and is therefore a major concern in aging populations. Body composition analysis is important in the evaluation of obesity and sarcopenia because it provides information about the distribution of body fat and muscle mass. It is also useful for monitoring nutritional status, disease severity, and the effectiveness of interventions, such as exercise, diet, and drugs, and thus helps assess overall health and longevity. Computed tomography, magnetic resonance imaging, and dual-energy X-ray absorptiometry are commonly used for this purpose. However, they have limitations, such as high cost, long measurement time, and radiation exposure. Instead, bioelectrical impedance analysis (BIA), which was introduced several decades ago and has undergone significant technological advancements, can be used. It is easily accessible, affordable, and importantly, poses no radiation risk, making it suitable for use in hospitals, fitness centers, and even at home. Herein, we review the recent technological developments and clinical applications of BIA to provide an updated understanding of BIA technology and its strengths and limitations.

Early Radiological Outcome of Hallux Valgus Corrective Surgery With an Intramedullary Plate: A Single-Center Case Series.

INTRODUCTION: Hallux valgus is a common foot deformity that can lead to significant pain and functional limitations. Minimally invasive corrective surgery is becoming increasingly popular. The aim of this study is to evaluate the radiological outcome of mini-open hallux valgus surgery using an intramedullary plate in Asian patients. METHODS: A series of seven patients (six females, one male) and 10 feet underwent hallux valgus correction surgery. Three of the patients had bilateral surgery. Age ranged from 31 to 54 years old. All patients had severe pain and functional limitations. The cases are mild to moderate in severity, of which the radiological parameters are the hallux valgus angle (HVA), intermetatarsal angle (IMA), and distal metatarsal articular angle (DMAA). A Bosch osteotomy (distal metatarsal osteotomy) is performed, and a locking plate was inserted into the medullary canal with the distal part of the plate displacing the metatarsal head laterally. The rotational deformity was corrected. The plate is fixed to the metatarsal head. Akin's osteotomy was performed in all cases. Patients were allowed to bear weight immediately after surgery and were followed up at regular intervals with serial radiographs.  Result: The follow-up period was three months. All patients were full weightbearing with minimal or no pain at three months. Wounds were well healed. Osteotomy sites were united, with significant radiological improvement (mean HVA: 24.1° to 7.2°; mean IMA: 17° to 7.8°; mean DMAA: 13.7° to 4.2°). CONCLUSION: Mini-open hallux valgus surgery using an intramedullary plate is a safe and effective technique that can lead to significant improvement in pain and function for mild to moderate hallux valgus. The modified placement of the plate into the medullary canal allows for a smaller incision while providing correction of the hallux valgus deformity.

IKKε-deficient macrophages impede cardiac repair after myocardial infarction by enhancing the macrophage-myofibroblast transition.

The regulatory role of the inhibitor of NF-kB kinase ε (IKKε) in postmyocardial infarction (MI) inflammation remains uncertain. Using an MI mouse model, we examined the cardiac outcomes of IKKε knockout (KO) mice and wild-type mice. We employed single-cell RNA sequencing (scRNA-seq) and phosphorylated protein array techniques to profile cardiac macrophages. IKKε KO mice exhibited compromised survival, heightened inflammation, pronounced cardiac fibrosis, and a reduced ejection fraction. A distinct cardiac macrophage subset in IKKε KO mice exhibited increased fibrotic marker expression and decreased phosphorylated p38 (p-p38) levels, indicating an enhanced macrophage-myofibroblast transition (MMT) post-MI. While cardiac inflammation is crucial for initiating compensatory pathways, the timely resolution of inflammation was impaired in the IKKε KO group, while the MMT in macrophages accelerated post-MI, leading to cardiac failure. Additionally, our study highlighted the potential of 5-azacytidine (5-Aza), known for its anti-inflammatory and cardioprotective effects, in restoring p-p38 levels in stimulated macrophages. The administration of 5-Aza significantly reduced the MMT in cardiac macrophages from the IKKε KO group. These findings underscore the regulation of the inflammatory response and macrophage transition by the IKKε-p38 axis, indicating that the MMT is a promising therapeutic target for ischemic heart disease.

Rising to the challenge of cardio-renal-metabolic disease in the 21st century: Translating evidence into best clinical practice to prevent and manage atherosclerosis.

Rising rates of obesity-associated cardiometabolic disorders allied to ageing populations are driving increases in cardiovascular morbidity and mortality. These adverse trends present challenges for healthcare systems that are struggling to prevent and manage the burgeoning cardiometabolic nexus of multiple long-term conditions. While potent new medications and non-pharmacological interventions have ushered in a promising new therapeutic era, translating clinical trial data to real-world clinical practice is often suboptimal. Postgraduate training and narrowly focused clinical specialisations reflect the traditional siloed approach to managing cardiovascular-metabolic disease that appears increasingly outmoded in the 21st century. It is our contention that greater inter-disciplinary collaboration allied to increased awareness of the continuum of cardiometabolic disease should enable clinicians to address this global public health threat more effectively. With this aim in mind, we have established an International Cardiometabolic Working Group. It is our hope to stimulate the interest of clinicians and clinical researchers across a range of medical specialties who share the vision of better care for people living with cardiometabolic diseases.

Superficial Anaplastic Lymphoma Kinase-Rearranged Myxoid Spindle Cell Neoplasm in the Buttock: A Case Report.

Anaplastic lymphoma kinase (ALK) is detected in both normal and oncological developmental tissues. Among ALK-related tumors, superficial ALK-rearranged myxoid spindle cell neoplasm (SAMS) is a rare, soft tissue tumor characterized by the immunophenotypical co-expression of CD34 and S100. Here, we describe a patient with this rare tumor and outline its clinical and radiological characteristics. A 28-year-old woman with diabetes, hypertension, and panic disorder presented with discomfort caused by a rubbery mass on the left buttock that had persisted for 10 years. Computed tomography revealed a multilobulated hypodense mass with small internal enhancing foci, posing challenges for the exact diagnosis of the lesion. The entire lesion was excised with clear resection margins. An 8.0 × 6.0 cm, well-circumscribed tumor with a lobular growth pattern was observed in the deep subcutaneous tissue. Light microscopy revealed epithelioid, ovoid, and spindle-shaped cells with a reticular cordlike pattern. Immunohistochemistry results were positive for S100, CD34, and vimentin. Break-apart fluorescence in situ hybridization assay results for ALK were also positive. These findings were consistent with those of SAMS. This case suggests that SAMS should be considered when identifying large nonspecific masses during clinical and imaging evaluation.

Association between glycemic status and all-cause mortality among individuals with dementia: a nationwide cohort study.

BACKGROUND: To examine the association between glycemic status and all-cause mortality risk among individuals with dementia. METHODS: We enrolled 146,832 individuals aged 40 and older with dementia as identified through the Korean National Health Insurance Service health screening test between 2008 and 2016. Mortality status was evaluated at the end of 2019. Participants were classified into normoglycemia, prediabetes, or diabetes mellitus (DM) categories. The duration of diabetes was noted in those with DM. This study focused on the association between glycemic status and all-cause mortality. RESULTS: The cohort, which was predominantly elderly (average age 75.1 years; 35.5% male), had a 35.2% mortality rate over an average 3.7-year follow-up. DM was linked with increased all-cause mortality risk (hazard ratio [HR] 1.34; 95% confidence interval [CI]: 1.32-1.37) compared to non-DM counterparts. The highest mortality risk was observed in long-term DM patients (≥ 5 years) (HR 1.43; 95% CI: 1.40-1.47), followed by newly diagnosed DM (HR 1.35; 95% CI: 1.30-1.40), shorter-term DM (< 5 years) (HR 1.17; 95% CI: 1.13-1.21), and prediabetes (HR 1.03; 95% CI: 1.01-1.05). These patterns persisted across Alzheimer's disease and vascular dementia, with more pronounced effects observed in younger patients. CONCLUSIONS: Glucose dysregulation in dementia significantly increased mortality risk, particularly in newly diagnosed or long-standing DM. These findings suggest the potential benefits of maintaining normal glycemic levels in improving the survival of patients with dementia.

Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE).

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Establishment of nanoparticle screening technique: A pivotal role of sodium carboxymethylcellulose in enhancing oral bioavailability of poorly water-soluble aceclofenac.

A novel nanoparticle screening technique was established to mostly enhance the aqueous solubility and oral bioavailability of aceclofenac using nanoparticle systems. Among the polymers investigated, sodium carboxymethylcellulose (Na-CMC) showed the greatest increase in drug solubility. Utilizing spray-drying technique, the solvent-evaporated solid dispersion (SESD), surface-attached solid dispersion (SASD), and solvent-wetted solid dispersion (SWSD) were prepared using aceclofenac and Na-CMC at a weight ratio of 1:1 in 50 % ethanol, distilled water, and ethanol, respectively. Using Na-CMC as a solid carrier, an aceclofenac-loaded liquid self-emulsifying drug delivery system was spray-dried and fluid-bed granulated together with microcrystalline cellulose, producing a solid self-nanoemulsifying drug delivery system (SNEDDS) and solid self-nanoemulsifying granule system (SNEGS), respectively. Their physicochemical properties and preclinical assessments in rats were performed. All nanoparticles exhibited very different properties, including morphology, crystallinity, and size. As a result, they significantly enhanced the solubility, dissolution, and oral bioavailability in the following order: SNEDDS ≥ SNEGS > SESD ≥ SASD ≥ SWSD. Based on our screening technique, the SNEDDS was selected as the optimal nanoparticle with the highest bioavailability of aceclofenac. Thus, our nanoparticle screening technique should be an excellent guideline for solubilization research to improve the solubility and bioavailability of many poorly water-soluble bioactive materials.

Efficacy and Safety of Pioglitazone Add-on in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin and Dapagliflozin: A Multicenter, Randomized, Double-blind, and Placebo-controlled Study.

PURPOSE: The purpose of this study was to determine the efficacy and safety profile of pioglitazone compared with placebo (PBO) in patients with type 2 diabetes (T2D) inadequately controlled with metformin and dapagliflozin. METHODS: In this prospective, multicenter, randomized, double-blind, PBO-controlled trial, 366 patients with T2D who did not meet glycemic targets (7.0% ≤ glycosylated hemoglobin [HbA1c] ≤ 10.5%), despite treatment with metformin ≥1000 mg and dapagliflozin 10 mg, received either a PBO, 15 mg of pioglitazone daily (PIO15), or 30 mg of pioglitazone daily (PIO30). The primary end point was the mean change in HbA1c from baseline at 24 weeks across the groups. FINDINGS: For the 366 participants (PBO, n = 124; PIO15, n = 118; PIO30, n = 124), the mean age was 55.6 years and mean duration of diabetes was 8.7 years, with a baseline HbA1c of 7.9%. After 24 weeks, HbA1c reduced significantly in the PIO15 and PIO30 groups from baseline, with intergroup differences of -0.38% and -0.83%, respectively, compared with the PBO group. The proportion of patients with HbA1c levels <7% was significantly higher in the PIO15 and PIO30 groups than in the PBO group. The adverse event rates did not significantly differ across the groups, indicating favorable safety profiles for triple combination therapy using metformin, dapagliflozin, and pioglitazone. IMPLICATIONS: The addition of pioglitazone as a third oral antidiabetic medication is an appropriate option for patients with T2D inadequately controlled with metformin and dapagliflozin based on the resulting significant efficacy in glycemic control and favorable safety profile. CLINICALTRIALS: gov identifier: NCT04885712.

Long-term comparison of renal and metabolic outcomes after sodium-glucose co-transporter 2 inhibitor or glucagon-like peptide-1 receptor agonist therapy in type 2 diabetes.

BACKGROUND: Renal outcomes in patients with type 2 diabetes following treatment with sodium-glucose co-transporter-2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP1RAs) have not been directly compared. This study compared the impact of SGLT2i and GLP1RA therapy on renal function and metabolic parameters. METHODS: Patients with type 2 diabetes who initiated SGLT2i or GLP1RA therapy in a tertiary hospital between January 2009 and August 2023 were included to assess composite renal outcomes, such as a 40% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease, renal death, or new-onset macroalbuminuria. Alterations in blood pressure, glucose regulation parameters, lipid profile, and anthropometric parameters, including body fat and muscle masses, were examined over 4-years. RESULTS: A total of 2,112 patients were enrolled using a one-to-three propensity-score matching approach (528 patients for GLP1RAs, 1,584 patients for SGLT2i). SGLT2i treatment was favoured over GLP1RA treatment, though not significantly, for composite renal outcomes (hazard ratio [HR], 0.63; p = 0.097). SGLT2i therapy preserved renal function effectively than GLP1RAs (decrease in eGFR, ≥ 40%; HR, 0.46; p = 0.023), with improving albuminuria regression (HR, 1.72; p = 0.036). SGLT2i therapy decreased blood pressure and body weight to a greater extent. However, more patients attained HbA1c levels < 7.0% with GLP1RAs than with SGLT2is (40.6% vs 31.4%; p < 0.001). GLP1RA therapy enhanced ß-cell function and decreased LDL-cholesterol levels below baseline values. CONCLUSIONS: SGLT2is were superior for preserving renal function and reducing body weight, whereas GLP1RAs were better for managing glucose dysregulation and dyslipidaemia.

Precision medicine in lupus nephritis.

Lupus nephritis (LN) is a prominent manifestation of systemic lupus erythematosus (SLE), characterized by diverse clinical and histopathological features, imposing a substantial burden on patients. Although the exact cause of SLE remain undetermined, several genetic, epigenetics, hormonal, and other factors are implicated in LN pathogenesis. The management of LN rely on invasive renal biopsies, while the standard therapy of the proliferative form of LN remains empirical and relies on indiscriminate immunosuppressants (IS). These treatments exhibit unsatisfactory remission rates, trigger recurrent renal flares, and entail grave adverse effects (ADEs). The advent of precision medicine into LN entails a concentrated effort to pinpoint essential biomarkers, reshaping the landscape of LN management. The primary objective of this review is to synthesize and summarize existing research findings by elucidating the most prevalent immunological, genetic, and epigenetic alterations and deliberate on management strategies that can pave the way for precision medicine in tackling LN. Novel clinical biomarker such as serum anti-complement component 1q (anti-C1q), with urinary markers including neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP1) and tumour necrosis-like weak inducers of apoptosis (TWEAK) are strongly correlated with LN. These biomarkers have good sensitivity and specificity and perform better than conventional biomarkers in assessing LN activity. Similarly, more renal-specific genetic and epigenetic alteration have been correlated with LN susceptibility and severity. This includes variants of hyaluronan synthase 2 (HAS2), and platelet-derived growth factor receptor alpha (PDGFRA). In the future, integrating clinical, genetic, epigenetic, and targeted therapies holds promise for guiding precision medicine and improving LN outcomes.

Immunobiotic Bacteria Attenuate Hepatic Fibrosis through the Modulation of Gut Microbiota and the Activation of Aryl-Hydrocarbon Receptors Pathway in Non-Alcoholic Steatohepatitis Mice.

SCOPE: Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease worldwide that can progress to liver fibrosis (LF). Probiotics have beneficial roles in reducing intestinal inflammation and gut-associated diseases, but their effects and mechanisms beyond the gut in attenuating the progression of LF are remained unclear. METHODS AND RESULTS: In a mouse model of NASH/LF induced by a methionine-choline deficient (MCD) diet, immunobiotics are administered to investigate their therapeutic effects. Results show that the MCD diet leads to liver inflammation, steatosis, and fibrosis, which are alleviated by immunobiotics. Immunobiotics reduces serum endotoxin and inflammatory markers while increasing regulatory cytokines and liver weight. They also suppress Th17 cells, known for producing inflammatory cytokines. Furthermore, immunobiotics mitigate collagen deposition and fibrogenic signaling in the liver, while restoring gut-barrier integrity and microbiota composition. Additionally, immunobiotics enhance the activation of the aryl hydrocarbon receptor (AhR) pathway in both colonic and liver tissues. CONCLUSIONS: Overall, these results demonstrate a novel insight into the mechanisms through which immunobiotic administration improves the gut health which in turn increases the AhR pathway and inhibits HSCs activation and fibrosis progression beyond the gut in the liver tissue of NASH/LF mice.

Effects of perioperative dexmedetomidine on delayed graft function following renal transplant: a systematic review and meta-analysis.

BACKGROUND: Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist with sedative and analgesic effects, has been suggested in recent studies to possess renoprotective properties. Dexmedetomidine may reduce the incidence of delayed graft function and contribute to effective pain control post-renal transplantation. The primary objective of this systematic review was to assess whether dexmedetomidine decreases the occurrence of delayed graft function in renal transplant patients. METHODS: Databases including MEDLINE, EMBASE, and CENTRAL were comprehensively searched from their inception until March 2023. The inclusion criteria covered all Randomized Clinical Trials (RCTs) and observational studies comparing dexmedetomidine to control in adult patients undergoing renal transplant surgery. Exclusions comprised case series and case reports. RESULTS: Ten RCTs involving a total of 1358 patients met the eligibility criteria for data synthesis. Compared to the control group, the dexmedetomidine group demonstrated a significantly lower incidence of delayed graft function (OR = 0.71, 95% CI 0.52-0.97, p = 0.03, GRADE: Very low, I2 = 0%). Dexmedetomidine also significantly prolonged time to initiation of rescue analgesia (MD = 6.73, 95% CI 2.32-11.14, p = 0.003, GRADE: Very low, I2 = 93%) and reduced overall morphine consumption after renal transplant (MD = -5.43, 95% CI -7.95 to -2.91, p < 0.0001, GRADE: Very low, I2 = 0%). The dexmedetomidine group exhibited a significant decrease in heart rate (MD = -8.15, 95% CI -11.45 to -4.86, p < 0.00001, GRADE: Very low, I2 = 84%) and mean arterial pressure compared to the control group (MD = -6.66, 95% CI -11.27 to -2.04, p = 0.005, GRADE: Very low, I2 = 87%). CONCLUSIONS: This meta-analysis suggests that dexmedetomidine may potentially reduce the incidence of delayed graft function and offers a superior analgesia profile as compared to control in adults undergoing renal transplants. However, the high degree of heterogeneity and inadequate sample size underscore the need for future adequately powered trials to confirm these findings.

Immunosuppression for adult steroid-dependent or frequently relapsing nephrotic syndrome: A systematic review and meta-analysis.

OBJECTIVE: There is limited evidence on which immunosuppressive agents produce the best outcomes for adult patients with steroid-dependent or frequently relapsing nephrotic syndrome (SDNS/FRNS). This review compares the remission rate and adverse effects of various immunosuppressants used. METHODS: Studies of adult patients with biopsy-proven SDNS/FRNS, administered any immunosuppressive agents and reported complete remission results as one of the clinical outcomes were included. Articles were independently screened by two researchers. ROBINS-I was used for risk of bias assessment. Random-effects model was used for statistical analysis and corresponding 95% confidence intervals (CIs) were calculated. RESULTS: 574 patients across 28 studies were included in the analysis. Patients receiving rituximab have a complete remission rate of 89% (95% CI = 83% to 94%; τ2 = 0.0070; I2 = 62%; overall p < 0.01, low certainty) and adverse event rate of 0.26, cyclosporine (CR 40%; 95% CI = 21% to 59%; τ2 = 0.0205; I2 = 55%; overall p = 0.08, low certainty), tacrolimus (CR 84%; 95% CI = 70% to 98%; τ2 = 0.0060; I2 = 33%; overall p = 0.21, moderate certainty), mycophenolate mofetil (CR 82%; 95% CI = 74% to 90%; τ2 < 0.0001; I2 = 15%; overall p = 0.32, moderate certainty) and cyclophosphamide (CR 79%; 95% CI = 69% to 89%; τ2 = 0; I2 = 0%; overall p = 0.52, moderate certainty). CONCLUSION: Among the commonly used immunosuppressive agents, only rituximab has a statistically significant effect in achieving complete remission among patients with SDNS/FRNS and has a relatively good safety profile, but this is limited by low quality of evidence with high degree of heterogeneity causing a lack of statistical power.

Efficacy and tolerability of initial triple combination therapy with metformin, dapagliflozin and saxagliptin compared with stepwise add-on therapy in drug-naïve patients with type 2 diabetes (TRIPLE-AXEL study): A multicentre, randomized, 104-week, open-label, active-controlled trial.

AIM: To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add-on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D). MATERIALS AND METHODS: This multicentre, randomized, 104-week, open-label trial randomized 105 patients with drug-naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104. RESULTS: HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was -2.56% in the TCT group vs. -2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P = .027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P < .001). TCT was well-tolerated and had fewer adverse events than SAT. CONCLUSIONS: Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients.

In between the cracks.

A 65-year-old man with end-stage renal failure, severe aortic stenosis, and triple vessel coronary artery disease was admitted for percutaneous coronary intervention to the left anterior descending artery prior to transcatheter aortic valve replacement.

Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

BACKGRUOUND: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. RESULTS: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. CONCLUSION: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.