[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100652193":3},{"organization":4,"outcomesModule":7,"designInfo":55,"detailedDescription":62,"studyPopulation":54,"armGroups":63,"interventions":80,"overallOfficials":54,"centralContacts":94,"locations":100,"responsibleParty":121,"collaborators":124,"id":127,"slug":128,"hasResults":129,"nctId":130,"briefTitle":131,"officialTitle":131,"acronym":132,"eligibilityCriteria":133,"healthyVolunteers":129,"sex":134,"minAge":135,"maxAge":136,"enrollmentInfo":137,"targetDuration":54,"studyType":140,"phases":141,"briefSummary":143,"conditions":144,"keywords":146,"overallStatus":103,"whyStopped":54,"lastUpdateSubmitDate":151,"lastUpdatePostDateStruct":152,"startDateStruct":155,"completionDateStruct":157,"leadSponsor":159,"locationsCount":160},{"fullName":5,"class":6},"University Medical Centre Ljubljana","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":54},[9],{"measure":10,"description":11,"timeFrame":12},"Change in skeletal muscle mitochondrial oxidative capacity","Skeletal muscle mitochondrial oxidative capacity will be assessed non-invasively using near-infrared spectroscopy (NIRS) over the flexor digitorum superficialis muscle of the non-dominant forearm. The recovery rate of tissue oxygen saturation (StO2) following submaximal muscular exercise and repeated brief arterial occlusions will be used as an index of mitochondrial oxidative capacity. This outcome will be compared across the three treatment arms to test the hypotheses that empagliflozin increases skeletal muscle oxidative capacity, that metformin does not alter oxidative capacity, and that combination therapy increases oxidative capacity to a lesser degree than empagliflozin monotherapy.","Baseline, Day 14, Month 1, Month 3, and Month 6",[14,17,21,24,27,30,33,36,39,42,45,48,51],{"measure":15,"description":16,"timeFrame":12},"Change in skeletal muscle microvascular reactivity","Description: Microvascular reactivity will be assessed using NIRS by measuring peak tissue oxygen saturation (StO2) and StO2 recovery rate following release of a transient brachial artery occlusion. This outcome will be compared across the three treatment arms to test the hypothesis that microvascular reactivity increases to a greater extent in the empagliflozin group compared with the metformin and combination therapy groups.",{"measure":18,"description":19,"timeFrame":20},"Change in body fat mass","Body fat mass will be assessed using whole-body dual-energy X-ray absorptiometry (DXA).","Baseline, Month 3, and Month 6",{"measure":22,"description":23,"timeFrame":20},"Change in lean body mass","Lean body mass will be assessed using whole-body dual-energy X-ray absorptiometry (DXA).",{"measure":25,"description":26,"timeFrame":20},"Change in body fat percentage","Total body fat percentage will be assessed using whole-body DXA.",{"measure":28,"description":29,"timeFrame":20},"Change in appendicular lean mass index","Appendicular lean mass indexed to height squared will be assessed using whole-body DXA, as a marker of skeletal muscle mass relevant to sarcopenia.",{"measure":31,"description":32,"timeFrame":20},"Change in appendicular lean mass","Appendicular (limb) lean mass will be assessed using whole-body DXA.",{"measure":34,"description":35,"timeFrame":20},"Change in lean mass index","Total body lean mass indexed to height squared will be assessed using whole-body DXA.",{"measure":37,"description":38,"timeFrame":12},"Change in glycemic control - fasting plasma glucose","Fasting plasma glucose will be measured at each study visit.",{"measure":40,"description":41,"timeFrame":12},"Change in glycemic control - HbA1c","Glycated hemoglobin (HbA1c) will be measured at each study visit.",{"measure":43,"description":44,"timeFrame":12},"Change in 6-minute walk distance","Physical performance will be assessed using the 6-minute walk test.",{"measure":46,"description":47,"timeFrame":12},"Change in maximal handgrip strength","Maximal handgrip strength will be assessed bilaterally using a dynamometer.",{"measure":49,"description":50,"timeFrame":12},"Change in physical activity level (IPAQ)","Physical activity level will be assessed using a questionnaire adapted from the International Physical Activity Questionnaire (IPAQ), capturing time spent in vigorous, moderate, walking, and sedentary activity.",{"measure":52,"description":53,"timeFrame":12},"Change in self-reported physical capacity","Participants will rate their subjective physical capacity on a scale from 1 (poor capacity) to 10 (able to sustain high-intensity exercise without difficulty).",null,{"allocation":56,"interventionModel":57,"interventionModelDescription":58,"primaryPurpose":59,"observationalModel":54,"timePerspective":54,"maskingInfo":60},"RANDOMIZED","PARALLEL","This is a parallel-group, three-arm interventional study. Participants with newly diagnosed type 2 diabetes will be randomized via a computer-generated sequence in a 1:1:1 ratio to one of three treatment arms: (1) empagliflozin monotherapy, (2) metformin monotherapy, or (3) combination therapy with empagliflozin and metformin. Each participant will remain in their assigned treatment arm for the full study duration (baseline through Month 6 follow-up). Outcomes will be compared across the three groups at matched timepoints (Day 14, Month 1, Month 3, Month 6) to evaluate the differential and combined effects of the two drug classes on skeletal muscle oxidative capacity and microvascular reactivity.","BASIC_SCIENCE",{"masking":61,"maskingDescription":54,"whoMasked":54},"NONE","Type 2 diabetes mellitus is associated with impaired skeletal muscle mitochondrial oxidative capacity and microvascular dysfunction, both of which contribute to reduced exercise tolerance and may precede overt clinical complications. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, such as empagliflozin, have demonstrated cardiovascular and renal benefits in patients with type 2 diabetes through mechanisms that extend beyond glycemic control, including possible effects on mitochondrial function and vascular reactivity. Metformin, the first-line pharmacological treatment for type 2 diabetes, has also been proposed to influence mitochondrial metabolism, though its comparative effect on skeletal muscle oxidative capacity remains incompletely characterized.\n\nThis is a prospective, randomized, open-label, interventional study comparing the effects of empagliflozin, metformin, and their combination on skeletal muscle oxidative capacity and microvascular reactivity in individuals with newly diagnosed type 2 diabetes. A total of 54 participants will be randomized in a 1:1:1 ratio (n=18 per group) to: (1) empagliflozin monotherapy, (2) metformin monotherapy, or (3) combination therapy with empagliflozin and metformin.\n\nStudy visits and procedures\n\nBaseline visit (Day 0): Participants will be informed of the study procedures and purpose at the diabetes outpatient clinic and invited to participate voluntarily. Those who agree will sign informed consent. Medical records will be reviewed (duration of type 2 diabetes, comorbidities and their treatment, current medications). A clinical examination will be performed, including height, weight, body mass index, blood pressure, and heart rate. Participants will complete a physical activity questionnaire (adapted in part from the International Physical Activity Questionnaire, IPAQ). Maximal handgrip strength will be measured bilaterally using a dynamometer, and a 6-minute walk test will be performed. Blood will be drawn and urine collected for laboratory parameters.\n\nParticipants will be instructed to attend each testing visit between 7:00 and 9:00 AM, fasting (12-hour overnight fast), having abstained from caffeine, tobacco, and alcohol, and having avoided moderate-to-vigorous physical activity for at least 24 hours beforehand. To minimize the confounding effect of increased limb use, all measurements will be performed on the non-dominant arm.\n\nWhole-body dual-energy X-ray absorptiometry (DXA) will be used to quantitatively assess body composition. An interstitial glucose monitoring sensor will be applied for the first month of follow-up. Near-infrared spectroscopy (NIRS) measurements will be performed over the flexor digitorum superficialis muscle of the non-dominant forearm at rest, after submaximal muscular work, and during transient brachial artery occlusion, allowing assessment of skeletal muscle oxidative capacity and microvascular reactivity (protocol below). Pharmacological antidiabetic treatment will then be initiated (empagliflozin, metformin, or the combination, per randomization).\n\nFollow-up visits (Day 14, Month 1, Month 3, Month 6): The same protocol will be repeated at each follow-up visit. Body composition will be reassessed at the Month 3 and Month 6 visits.\n\nNIRS sub-protocol Tissue oxygen saturation (StO2) will be measured over the flexor digitorum superficialis muscle using a tissue spectrometer. Three sequential measurements will be obtained: (A) resting StO2 after 5 minutes of rest; (B) StO2 during submaximal handgrip exercise (60% of maximal grip force) interspersed with brief arterial occlusions, used to derive an index of mitochondrial oxidative capacity from the StO2 recovery rate; and (C) StO2 during and following a transient brachial artery occlusion, used to assess microvascular reactivity (peak StO2 and recovery rate after cuff release).\n\nSample size Sample size was estimated from published values of skeletal muscle oxidative capacity in healthy individuals (2.0 ± 0.3 min-¹), assuming a 20% reduction at baseline in participants with diabetes and a shift toward normal values with empagliflozin treatment (1.7 ± 0.3 min-¹ vs. 2.0 ± 0.3 min-¹), with no effect expected from metformin. With alpha = 0.05 and power = 0.8, at least 16 participants per group are required; 18 per group will be enrolled to allow for dropout.\n\nStatistical analysis Treatment-related changes will be analyzed using one-way repeated measures ANOVA with appropriate post-hoc testing. A P-value less than 0.05 will be considered statistically significant. Statistical analysis will be performed using MedCalc v14 (MedCalc Software bvba).\n\nThis study is conducted as a defined sub-study within a larger parent trial evaluating the effects of empagliflozin, metformin, and their combination on skeletal muscle function in individuals with type 2 diabetes (ethics approval by the Republic of Slovenia National Medical Ethics Committee, No. 0120-32\u002F2024-2711-3). This sub-study applies more restrictive inclusion criteria to a homogeneous subgroup of participants (male, aged 40-60 years, BMI 25-35 kg\u002Fm²) to minimize confounding related to sex, age, and body composition when assessing the primary outcome of skeletal muscle oxidative capacity.",[64,70,75],{"label":65,"type":66,"description":67,"interventionNames":68},"Empagliflozin","ACTIVE_COMPARATOR","Participants with newly diagnosed type 2 diabetes will receive empagliflozin monotherapy for 6 months.",[69],"Drug: Empagliflozin (Jardiance®)",{"label":71,"type":66,"description":72,"interventionNames":73},"Metformin","Participants with newly diagnosed type 2 diabetes will receive metformin monotherapy for 6 months.",[74],"Drug: Metformin",{"label":76,"type":66,"description":77,"interventionNames":78},"Empagliflozin + Metformin","Participants with newly diagnosed type 2 diabetes will receive combination therapy with empagliflozin and metformin for 6 months.",[79],"Combination Product: Synjardy® 12.5mg\u002F1000mg film-coated tablets",[81,86,89],{"type":82,"name":83,"description":84,"armGroupLabels":85,"otherNames":54},"DRUG","Empagliflozin (Jardiance®)","Empagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor administered orally at a standard therapeutic dose for the treatment of type 2 diabetes mellitus. In this study, empagliflozin will be administered alone (Arm 1) or in combination with metformin (Arm 3) for 6 months, with skeletal muscle oxidative capacity and microvascular reactivity assessed at baseline and follow-up visits.",[65],{"type":82,"name":71,"description":87,"armGroupLabels":88,"otherNames":54},"Metformin is a biguanide antihyperglycemic agent administered orally at a standard therapeutic dose for the treatment of type 2 diabetes mellitus. In this study, metformin will be administered alone (Arm 2) or in combination with empagliflozin (Arm 3) for 6 months, with skeletal muscle oxidative capacity and microvascular reactivity assessed at baseline and follow-up visits.",[71],{"type":90,"name":91,"description":92,"armGroupLabels":93,"otherNames":54},"COMBINATION_PRODUCT","Synjardy® 12.5mg\u002F1000mg film-coated tablets","Fixed-dose combination product containing empagliflozin and metformin, administered orally at standard therapeutic doses for the treatment of type 2 diabetes mellitus. Used in the combination therapy arm (Arm 3) for 6 months, with skeletal muscle oxidative capacity and microvascular reactivity assessed at baseline and follow-up visits.",[76],[95],{"name":96,"role":97,"phone":98,"phoneExt":54,"email":99},"Eva Podbregar Kolar, MD","CONTACT","+38640762768","evapodbregar@gmail.com",[101],{"facility":102,"status":103,"city":104,"state":54,"zip":105,"country":106,"countryCode":107,"cosmosGeoPoint":108,"geoPoint":113,"contacts":114},"UMC Ljubljana","RECRUITING","Ljubljana","1000","Slovenia","SI",{"type":109,"coordinates":110},"Point",[111,112],14.50513,46.05108,{"lat":112,"lon":111},[115,116,119],{"name":96,"role":97,"phone":98,"phoneExt":54,"email":99},{"name":117,"role":97,"phone":54,"phoneExt":54,"email":118},"Mojca Lunder, MD PhD","mojca.lunder@kclj.si",{"name":96,"role":120,"phone":54,"phoneExt":54,"email":54},"PRINCIPAL_INVESTIGATOR",{"type":120,"investigatorFullName":122,"investigatorTitle":123,"investigatorAffiliation":5,"oldNameTitle":54,"oldOrganization":54},"Eva Podbregar Kolar","MD",[125],{"name":126,"class":6},"University of Ljubljana, Faculty of Medicine","100652193","phase-4-the-effect-of-empagliflozin-and-metformin-on-oxidative-capacity-and-microvascular-reactivity-of-skeletal-muscle-in-patients-with-type-2-diabetes-mellitus-100652193",false,"NCT07771010","The Effect of Empagliflozin and Metformin on Oxidative Capacity and Microvascular Reactivity of Skeletal Muscle in Patients With Type 2 Diabetes Mellitus","EMPOWER","Inclusion Criteria:\n\n* Male sex\n* Age 18-75 years\n* Newly diagnosed type 2 diabetes mellitus, confirmed no more than 2 years prior to enrollment\n* Body mass index (BMI) 25-35 kg\u002Fm²\n* Currently managed at a diabetes outpatient clinic\n* No known chronic diabetes-related complications\n* No prior antidiabetic pharmacological treatment, with the exception of sulfonylureas\n\nExclusion Criteria:\n\n* Other forms of diabetes mellitus (i.e., not type 2)\n* Type 2 diabetes mellitus known for more than 2 years\n* Comorbidities known to independently affect skeletal muscle oxidative capacity, including: spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, cystic fibrosis, local joint immobility, or hemiplegia\n* Known mitochondrial disease\n* Heart failure, NYHA class II or higher\n* Chronic kidney disease, stage 3 or higher\n* Poorly controlled chronic medical conditions (e.g., arterial hypertension, hypothyroidism)\n* Recurrent urinary tract infections\n* Active malignancy currently undergoing oncologic treatment\n* Life expectancy less than 3 months\n* Symptomatic hyperglycemia with fasting plasma glucose above 18 mmol\u002FL, HbA1c ≥ 10%\n* Unwillingness to provide informed consent","MALE","18 Years","75 Years",{"count":138,"type":139},54,"ESTIMATED","INTERVENTIONAL",[142],"PHASE4","The purpose of the study is to compare the effect of empagliflozin, metformin, and the combination of both on the oxidative capacity of skeletal muscle and its microvascular reactivity in individuals with newly diagnosed type 2 diabetes. As the primary outcome, the investigators selected the change in skeletal muscle oxidative capacity and posed the following scientific question: Does empagliflozin significantly improve the oxidative capacity of skeletal muscle? The study will enroll 54 individuals with type 2 diabetes in a prospective, randomized, interventional, open-label study. Participants will be randomized into 3 equally sized groups: 1) a group receiving empagliflozin; 2) a group receiving metformin; and 3) a group receiving a combination of both drugs (empagliflozin and metformin). The investigators will analyze the clinical variables of the subjects, near-infrared spectroscopy (NIRS) measurements over the flexor digitorum superficialis muscle of the non-dominant arm at rest, after submaximal muscular work, and during transient brachial artery occlusion at specified time intervals (14 days, 1 month, 3 months, 6 months), as well as body composition, physical performance, and glycemic control following the pharmacological intervention.",[145],"Diabetes Type 2",[147,65,71,148,149,150],"type 2 diabetes mellitus","Skeletal muscle oxidative capacity","Near-infrared spectroscopy","Microvascular reactivity","2026-08-13",{"date":153,"type":154},"2026-08-18","ACTUAL",{"date":156,"type":154},"2026-04-16",{"date":158,"type":139},"2028-07-31",{"name":5,"class":6},1]