Diabetes Type 2Phase 4EMPOWERNCT07771010
The Effect of Empagliflozin and Metformin on Oxidative Capacity and Microvascular Reactivity of Skeletal Muscle in Patients With Type 2 Diabetes Mellitus
A Phase 4 study testing Empagliflozin (Jardiance®), Metformin and Synjardy® 12.5mg/1000mg film-coated tablets in people with Diabetes Type 2, run by University Medical Centre Ljubljana at 1 site in Slovenia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years, men only
- Conditions the study is for
- Diabetes Type 2
- What is being tested?
- Empagliflozin (Jardiance®), Metformin and Synjardy® 12.5mg/1000mg film-coated tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteSlovenia
- Study dates
- 16 Apr 2026to 31 Jul 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male sex
- Age 18-75 years
- Newly diagnosed type 2 diabetes mellitus, confirmed no more than 2 years prior to enrollment
- Body mass index (BMI) 25-35 kg/m²
- Currently managed at a diabetes outpatient clinic
- No known chronic diabetes-related complications
- No prior antidiabetic pharmacological treatment, with the exception of sulfonylureas
Who cannot join
- Other forms of diabetes mellitus (i.e., not type 2)
- Type 2 diabetes mellitus known for more than 2 years
- 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
- Known mitochondrial disease
- Heart failure, NYHA class II or higher
- Chronic kidney disease, stage 3 or higher
Show all 12Show fewer
- Poorly controlled chronic medical conditions (e.g., arterial hypertension, hypothyroidism)
- Recurrent urinary tract infections
- Active malignancy currently undergoing oncologic treatment
- Life expectancy less than 3 months
- Symptomatic hyperglycemia with fasting plasma glucose above 18 mmol/L, HbA1c ≥ 10%
- Unwillingness to provide informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Slovenia1 site, 1 recruiting
- Recruiting
UMC Ljubljana
Ljubljana, 1000
Eva Podbregar Kolar, MD, +38640762768, evapodbregar@gmail.com
Mojca Lunder, MD PhD, mojca.lunder@kclj.si
About this study
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.
Read the detailed description
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.
This 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.
Study visits and procedures
Baseline 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.
Participants 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.
Whole-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).
Follow-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.
NIRS 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).
Sample 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.
Statistical 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).
This 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. 0120-32/2024-2711-3). This sub-study applies more restrictive inclusion criteria to a homogeneous subgroup of participants (male, aged 40-60 years, BMI 25-35 kg/m²) to minimize confounding related to sex, age, and body composition when assessing the primary outcome of skeletal muscle oxidative capacity.
- Conditions
- Diabetes Type 2
- Being tested
- Empagliflozin (Jardiance®), Metformin, Synjardy® 12.5mg/1000mg film-coated tablets
- Keywords
- type 2 diabetes mellitus, Empagliflozin, Metformin, Skeletal muscle oxidative capacity, Near-infrared spectroscopy, Microvascular reactivity
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin (Jardiance®)Drug
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.
MetforminDrug
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.
Synjardy® 12.5mg/1000mg film-coated tabletsCombination product
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.
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin | Active comparator | Participants with newly diagnosed type 2 diabetes will receive empagliflozin monotherapy for 6 months. Receives: Drug: Empagliflozin (Jardiance®) |
| Metformin | Active comparator | Participants with newly diagnosed type 2 diabetes will receive metformin monotherapy for 6 months. Receives: Drug: Metformin |
| Empagliflozin + Metformin | Active comparator | Participants with newly diagnosed type 2 diabetes will receive combination therapy with empagliflozin and metformin for 6 months. Receives: Combination Product: Synjardy® 12.5mg/1000mg film-coated tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Day 14, Month 1, Month 3, and Month 6
Secondary outcomes (13)
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.
Measured: Baseline, Day 14, Month 1, Month 3, and Month 6
Change in body fat mass
Body fat mass will be assessed using whole-body dual-energy X-ray absorptiometry (DXA).
Measured: Baseline, Month 3, and Month 6
Change in lean body mass
Lean body mass will be assessed using whole-body dual-energy X-ray absorptiometry (DXA).
Measured: Baseline, Month 3, and Month 6
Change in body fat percentage
Total body fat percentage will be assessed using whole-body DXA.
Measured: Baseline, Month 3, and Month 6
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.
Measured: Baseline, Month 3, and Month 6
Change in appendicular lean mass
Appendicular (limb) lean mass will be assessed using whole-body DXA.
Measured: Baseline, Month 3, and Month 6
Change in lean mass index
Total body lean mass indexed to height squared will be assessed using whole-body DXA.
Measured: Baseline, Month 3, and Month 6
Change in glycemic control - fasting plasma glucose
Fasting plasma glucose will be measured at each study visit.
Measured: Baseline, Day 14, Month 1, Month 3, and Month 6
Change in glycemic control - HbA1c
Glycated hemoglobin (HbA1c) will be measured at each study visit.
Measured: Baseline, Day 14, Month 1, Month 3, and Month 6
Change in 6-minute walk distance
Physical performance will be assessed using the 6-minute walk test.
Measured: Baseline, Day 14, Month 1, Month 3, and Month 6
Change in maximal handgrip strength
Maximal handgrip strength will be assessed bilaterally using a dynamometer.
Measured: Baseline, Day 14, Month 1, Month 3, and Month 6
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.
Measured: Baseline, Day 14, Month 1, Month 3, and Month 6
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).
Measured: Baseline, Day 14, Month 1, Month 3, and Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2026
- Study start16 Apr 2026
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Diabetes Type 2Studies of the same condition, open and under way.
- More trials run by University Medical Centre LjubljanaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Collaborators
- University of Ljubljana, Faculty of Medicine
- Responsible party
- Principal investigator, Eva Podbregar Kolar, University Medical Centre Ljubljana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07771010
- Sponsor's protocol ID
- 0120-32/2024-2711-3
- Acronym
- EMPOWER
- Status last verified
- Aug 2026
- First submitted
- 20 Jul 2026
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: A decision regarding sharing of individual participant data with external researchers has not yet been made. This will be determined based on institutional data governance requirements, ethics committee guidance, and journal submission requirements at the time of study completion.
Publications
Erickson ML, Ryan TE, Backus D, McCully KK. Endurance neuromuscular electrical stimulation training improves skeletal muscle oxidative capacity in individuals with motor-complete spinal cord injury. Muscle Nerve. 2017 May;55(5):669-675. doi: 10.1002/mus.25393. Epub 2017 Jan 11.
PubMed 27576602Ryan TE, Brophy P, Lin CT, Hickner RC, Neufer PD. Assessment of in vivo skeletal muscle mitochondrial respiratory capacity in humans by near-infrared spectroscopy: a comparison with in situ measurements. J Physiol. 2014 Aug 1;592(15):3231-41. doi: 10.1113/jphysiol.2014.274456. Epub 2014 Jun 20.
PubMed 24951618Ryan TE, Southern WM, Reynolds MA, McCully KK. A cross-validation of near-infrared spectroscopy measurements of skeletal muscle oxidative capacity with phosphorus magnetic resonance spectroscopy. J Appl Physiol (1985). 2013 Dec;115(12):1757-66. doi: 10.1152/japplphysiol.00835.2013. Epub 2013 Oct 17.
PubMed 24136110Brizendine JT, Ryan TE, Larson RD, McCully KK. Skeletal muscle metabolism in endurance athletes with near-infrared spectroscopy. Med Sci Sports Exerc. 2013 May;45(5):869-75. doi: 10.1249/MSS.0b013e31827e0eb6.
PubMed 23247709Hagstromer M, Oja P, Sjostrom M. The International Physical Activity Questionnaire (IPAQ): a study of concurrent and construct validity. Public Health Nutr. 2006 Sep;9(6):755-62. doi: 10.1079/phn2005898.
PubMed 16925881
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Empagliflozin and Metformin on Oxidative Capacity and Microvascular Reactivity of Skeletal Muscle in Patients With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT07771010
- Acronym / sponsor ID
- EMPOWER / 0120-32/2024-2711-3
- Conditions
- Diabetes Type 2
- Keywords
- type 2 diabetes mellitus, Empagliflozin, Metformin, Skeletal muscle oxidative capacity, Near-infrared spectroscopy, Microvascular reactivity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Collaborators
- University of Ljubljana, Faculty of Medicine
- Study start
- 16 Apr 2026 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Jul 2028 (estimated)
- First posted
- 18 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
This 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.
Study visits and procedures
Baseline 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.
Participants 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.
Whole-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).
Follow-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.
NIRS 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).
Sample 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.
Statistical 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).
This 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. 0120-32/2024-2711-3). This sub-study applies more restrictive inclusion criteria to a homogeneous subgroup of participants (male, aged 40-60 years, BMI 25-35 kg/m²) to minimize confounding related to sex, age, and body composition when assessing the primary outcome of skeletal muscle oxidative capacity.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin | Active comparator | Drug: Empagliflozin (Jardiance®)Participants with newly diagnosed type 2 diabetes will receive empagliflozin monotherapy for 6 months. |
| Metformin | Active comparator | Drug: MetforminParticipants with newly diagnosed type 2 diabetes will receive metformin monotherapy for 6 months. |
| Empagliflozin + Metformin | Active comparator | Combination Product: Synjardy® 12.5mg/1000mg film-coated tabletsParticipants with newly diagnosed type 2 diabetes will receive combination therapy with empagliflozin and metformin for 6 months. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male sex
- Age 18-75 years
- Newly diagnosed type 2 diabetes mellitus, confirmed no more than 2 years prior to enrollment
- Body mass index (BMI) 25-35 kg/m²
- Currently managed at a diabetes outpatient clinic
Key exclusion criteria (12 listed)
- Other forms of diabetes mellitus (i.e., not type 2)
- Type 2 diabetes mellitus known for more than 2 years
- 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
- Known mitochondrial disease
- Heart failure, NYHA class II or higher
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Empagliflozin |
| MetforminMetformin 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. | Drug | Metformin |
| Synjardy® 12.5mg/1000mg film-coated tabletsFixed-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. | Combination product | Empagliflozin + Metformin |
Primary outcome
Change in skeletal muscle mitochondrial oxidative capacity
Time frame: Baseline, Day 14, Month 1, Month 3, and Month 6
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.
13 secondary outcomes
Change in skeletal muscle microvascular reactivity
Time frame: Baseline, Day 14, Month 1, Month 3, and Month 6
Change in body fat mass
Time frame: Baseline, Month 3, and Month 6
Change in lean body mass
Time frame: Baseline, Month 3, and Month 6
Change in body fat percentage
Time frame: Baseline, Month 3, and Month 6
Change in appendicular lean mass index
Time frame: Baseline, Month 3, and Month 6
Change in appendicular lean mass
Time frame: Baseline, Month 3, and Month 6
Change in lean mass index
Time frame: Baseline, Month 3, and Month 6
Change in glycemic control - fasting plasma glucose
Time frame: Baseline, Day 14, Month 1, Month 3, and Month 6
Change in glycemic control - HbA1c
Time frame: Baseline, Day 14, Month 1, Month 3, and Month 6
Change in 6-minute walk distance
Time frame: Baseline, Day 14, Month 1, Month 3, and Month 6
Change in maximal handgrip strength
Time frame: Baseline, Day 14, Month 1, Month 3, and Month 6
Change in physical activity level (IPAQ)
Time frame: Baseline, Day 14, Month 1, Month 3, and Month 6
Change in self-reported physical capacity
Time frame: Baseline, Day 14, Month 1, Month 3, and Month 6
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- Background: PubMed 27576602Erickson ML, Ryan TE, Backus D, McCully KK. Endurance neuromuscular electrical stimulation training improves skeletal muscle oxidative capacity in individuals with motor-complete spinal cord injury. Muscle Nerve. 2017 May;55(5):669-675. doi: 10.1002/mus.25393. Epub 2017 Jan 11.
- Background: PubMed 24951618Ryan TE, Brophy P, Lin CT, Hickner RC, Neufer PD. Assessment of in vivo skeletal muscle mitochondrial respiratory capacity in humans by near-infrared spectroscopy: a comparison with in situ measurements. J Physiol. 2014 Aug 1;592(15):3231-41. doi: 10.1113/jphysiol.2014.274456. Epub 2014 Jun 20.
- Background: PubMed 24136110Ryan TE, Southern WM, Reynolds MA, McCully KK. A cross-validation of near-infrared spectroscopy measurements of skeletal muscle oxidative capacity with phosphorus magnetic resonance spectroscopy. J Appl Physiol (1985). 2013 Dec;115(12):1757-66. doi: 10.1152/japplphysiol.00835.2013. Epub 2013 Oct 17.
- Background: PubMed 23247709Brizendine JT, Ryan TE, Larson RD, McCully KK. Skeletal muscle metabolism in endurance athletes with near-infrared spectroscopy. Med Sci Sports Exerc. 2013 May;45(5):869-75. doi: 10.1249/MSS.0b013e31827e0eb6.
- Background: PubMed 16925881Hagstromer M, Oja P, Sjostrom M. The International Physical Activity Questionnaire (IPAQ): a study of concurrent and construct validity. Public Health Nutr. 2006 Sep;9(6):755-62. doi: 10.1079/phn2005898.
- Individual participant dataSharing planned: Undecided. A decision regarding sharing of individual participant data with external researchers has not yet been made. This will be determined based on institutional data governance requirements, ethics committee guidance, and journal submission requirements at the time of study completion.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Empagliflozin (Jardiance®), Metformin and Synjardy® 12.5mg/1000mg film-coated tablets in people with Diabetes Type 2, run by University Medical Centre Ljubljana at 1 site in Slovenia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Eva Podbregar Kolar, MD (+38640762768, evapodbregar@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in skeletal muscle mitochondrial oxidative capacity (time frame: Baseline, Day 14, Month 1, Month 3, and Month 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07771010, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026.