Type 2 Diabetes Mellitus (T2DM)Phase 4E-SEMPANCT06613854
Effect of Early Combination Antihyperglycemic Treatment on Metabolic Control in Individuals With Type 2 Diabetes
A Phase 4 study testing Oral semaglutide and Empagliflozin 10 mg in people with Type 2 Diabetes Mellitus (T2DM), run by University Medical Centre Ljubljana at 1 site in Slovenia.
Trial summary
The goal of this clinical trial is to learn if early combination with two antidiabetic drugs further improves blood glucose control compared to a single drug regimen in adults with short duration of type 2 diabetes. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Type 2 Diabetes Mellitus (T2DM)
- What is being tested?
- Oral semaglutide and Empagliflozin 10 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteSlovenia
- Study dates
- 1 Oct 2024to Dec 2027
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with type 2 diabetes for up to 2 years (prior to randomization);
- Aged between 18 and 70 years, both sexes, of any race or ethnicity;
- HbA1c ≤8.0% at randomization;
- Baseline treatment with metformin at a steady daily dose of ≥1500 mg;
- Signed informed consent to participate in the study.
Who cannot join
- Treatment at any time in the past with SGLT2i, GLP-1RA, or DPP-4 inhibitors;
- Insulin treatment for longer than 2 weeks in the past;
- Body Mass Index below 22 kg/m2 or BMI above 40 kg/m2;
- Chronic kidney disease stages 3-5 (eGFR below 60 ml/min or the presence of albuminuria (urine albumin-to-creatinine ratio above 34 g/mmol);
- Known cardiovascular disease (angina pectoris, history of myocardial infarction, ischemic heart disease, heart failure, known carotid atherosclerosis, objectively proven peripheral arterial disease, or other known atherosclerotic disease at other locations);
- Moderate or severe liver disease (Child-Pugh stage B or C);
Show all 23Show fewer
- Personal history of pancreatitis;
- Advanced heart failure (NYHA III-IV);
- Retinopathy or maculopathy or their active treatment;
- Pregnancy, expected pregnancy, or breastfeeding;
- Presence of active malignancy or personal history of malignancy within 5 years of study enrollment;
- Personal history of thyroid cancer; personal or family history of multiple endocrine neoplasia type 2 or family history of medullary thyroid carcinoma;
- Chronic inflammatory bowel disease;
- History of bariatric surgery or other gastrointestinal surgery that could affect drug or nutrient absorption;
- Frequent or severe urinary tract infections;
- Presence of a urinary catheter;
- Troublesome and recurrent genital fungal infections;
- Personal history of ketoacidosis;
- Symptomatic hypotension or predisposition to hypovolemia;
- History of organ transplantation;
- Allergy to any component in the semaglutide or empagliflozin oral tablet;
- Any medical or social circumstance that may limit participation in the study (e.g., inability to attend regular study visits);
- Any other condition that, in the opinion of the principal and responsible investigators, may affect the safety or efficacy of the treatment.
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
University Medical Centre Ljubljana, Diabetes Outpatient Clinic
Ljubljana, 1000
Jaka Sikonja, MD, +38640778882, jaka.sikonja@kclj.si
Andrej Janez, MD, PhD
About this study
Official title: Effect of Early Combination Antihyperglycemic Treatment With Metformin and Oral Semaglutide vs. Metformin and Empagliflozin on Glycemic and Metabolic Control in Individuals With Short Duration Type 2 Diabetes
The goal of this clinical trial is to learn if early combination with two antidiabetic drugs further improves blood glucose control compared to a single drug regimen in adults with short duration of type 2 diabetes. It will also learn about the effect of the combination treatment on body weight, body composition, blood lipids, oxidative stress, inflammation, metabolic control, insulin resistance and insulin secretion from pancreas, together with its safety profile. The main questions it aims to answer are:
- Does early combination with two antidiabetic drugs improve blood glucose levels, determined by continuous glucose monitoring system?
- Is early combination treatment as safe as treatment with a single antidiabetic drug?
- Does early combination treatment reduces the need for rescue therapy?
- Does early combination treatment reduces body weight and improves body composition?
- Does early combination treatment improves blood lipid parameters, oxidative stress and inflammation?
- Does early combination treatment improves metabolic parameters?
- Does early combination treatment improves insulin resistance and insulin secretion?
Read more
Researchers will compare early combination treatment with metformin and either peroral semaglutide or empagliflozin to a single drug regimen with only metformin to see if the combination treatment works to treat type 2 diabetes.
Participants will:
- Take the combination of two antidiabetic drugs or only metformin for every day for 26 weeks.
- Visit the clinic four times during the study duration for checkups and tests.
- Carry a continuous glucose monitoring sensor for 14 days prior to study visits.
Read the detailed description
Type 2 diabetes (T2D) is a progressive chronic disease and represents a significant risk factor for morbidity and mortality due to cardiovascular disease. In addition to managing glycemia, the use of antihyperglycemic medications with further and independent cardiovascular benefits is recommended in managing individuals with T2D. These medications primarily include sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). Traditionally, treatment of T2D followed a stepwise intensification by adding antihyperglycemic drugs if optimal glycemic control was not achieved. However, current American Diabetes Association guidelines recommend considering early combination therapy at treatment initiation, particularly at high baseline glycated hemoglobin (HbA1c) levels, to shorten the time to achieve glycemic goals.
In everyday clinical practice, however, treatment intensification is often delayed due to clinical inertia, even when glycemic control is suboptimal. Early intensive treatment of T2D has been shown to improve glycemic control, reduce mortality, and lower the risk of both microvascular and macrovascular complications, while also improving the durability of the glycemic effect.
Previous randomized clinical trials on early combination therapy for T2D have primarily focused on glycemic control, as determined by traditional glycemic parameters such as fasting glucose and HbA1c. However, new insights suggest that these measures alone are insufficient for a holistic assessment of glycemic control in diabetes. There is now a recognized need to consider additional indicators of glycemic control, obtained through continuous glucose monitoring (CGM) systems. Furthermore, data are lacking on the direct comparison of the early combination treatment with either SGLT2i or GLP-1RA on top of metformin.
In this 26-week, prospective, open-label, interventional, randomized, single-center clinical trial with a 3-week run-in period, we aim to investigate the effect of early combination treatment with metformin and GLP-1RA or SGLT2i compared to standard monotherapy with metformin and subsequent escalation of antihyperglycemic treatment on glycemic control, as assessed by continuous glucose monitoring systems and HbA1c, body weight, body composition, lipid profile, oxidative stress, inflammation, metabolic control, insulin resistance, and pancreatic beta-cell function in adults with short duration T2D. The primary outcome of the study will be glycemic control, assessed by time in range (TIR).
The study will include individuals of both sexes, of any race or ethnicity, aged between 18 and 70, with a duration of T2D of less than 2 years, HbA1c levels ≤8.0%, on monotherapy with metformin, and naive to treatment with GLP-1RA and SGLT2i.
After the initial 3-week run-in period, patients will be randomized (based on sex, age, and TIR during the run-in period) into three intervention groups in a 1:1:1 ratio:
(i) a control group, continuing metformin monotherapy; (ii) the first study group, receiving metformin and oral semaglutide; and (iii) the second study group, receiving metformin and empagliflozin.
Patients will then be monitored approximately every 13 weeks (3 months) up to 26 weeks (6 months). Prior to randomization, participants will receive a study package containing 3 sensors and 1 reader of the CGM system. The first sensor will be placed on the participants at the start of the run-in period, and subsequent sensors will be self-applied by participants at least 14 days before the last two study visits (at week 13 and week 26).
At each study visit, a review of medical records, a clinical examination, and blood collection for laboratory tests will be conducted. At randomization (week 0) and during the final study visit (week 26), all participants will undergo a modified oral glucose tolerance test (mOGTT) to assess insulin resistance and pancreatic beta-cell function. Additionally, the first 20 participants from each intervention group will undergo whole-body imaging to evaluate body composition. In the case of inadequately controlled glycemia, rescue treatment with gliclazide from the sulfonylurea class will be initiated.
- Conditions
- Type 2 Diabetes Mellitus (T2DM)
- Being tested
- Oral semaglutide, Empagliflozin 10 mg
- Keywords
- E-SEMPA, Early Combination Antihyperglycemic Treatment, Metformin, Semaglutide, Empagliflozin, Glycemic Control, Metabolic Control, Type 2 Diabetes, Insulin Resistance, Time in Range, CGM, Continuous Glucose Monitoring, UMC Ljubljana
- Medical subject headings
- Diabetes Mellitus, Type 2, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral semaglutideDrug
Also called Rybelsus
Semaglutide Oral Tablets will be introduced to the Oral Semaglutide Arm as per protocol for regular therapy introduction.
Empagliflozin 10 mgDrug
Also called Jardiance
Empagliflozin Oral Tablets will be introduced to the Empagliflozin Arm as per protocol for regular therapy introduction.
| Study group | Role | What they receive |
|---|---|---|
| Oral Semaglutide Arm | Active comparator | Participants will receive oral semaglutide in addition to metformin (in a steady daily dose of ≥1500 mg), starting with an initial dose of 3 mg. The dose of semaglutide will be increased to 7 mg after 30 days, and then to a maintenance dose of 14 mg once daily after another 30 days that will be continued to week 26. In the case of inadequately controlled glycemia (HbA1c >8.0 % or symptomatic hyperglycemia), rescue treatment with gliclazide will be initiated. Receives: Drug: Oral semaglutide |
| Empagliflozin Arm | Active comparator | Participants will receive oral empagliflozin in a once daily dose of 10 mg in addition to metformin (in a steady daily dose of ≥1500 mg). The dose of empagliflozin will not be subsequently changed during the duration of the study. In the case of inadequately controlled glycemia (HbA1c >8.0 % or symptomatic hyperglycemia), rescue treatment with gliclazide will be initiated. Receives: Drug: Empagliflozin 10 mg |
| Control Arm | No intervention | Participants will receive metformin in a steady daily dose of ≥1500 mg. In the case of inadequately controlled glycemia (HbA1c >8.0 % or symptomatic hyperglycemia), rescue treatment with gliclazide will be initiated. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time in Range (TIR)
Defined as the time (or percentage of measurements) when the glucose value in the interstitial fluid is in the range of 3.9-10.0 mmol/L. Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in % or in hours and minutes).
Measured: Period of 14 days prior to last study visit (week 26)
Secondary outcomes (22)
Absolute Change in Time in Range (TIR)
Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in % or in hours and minutes).
Measured: Baseline (week 0) and last study visit (week 26)
Absolute Change in Glycated hemoglobin (HbA1c)
Assessment by biochemical methods (in %)
Measured: Baseline (week 0) and last study visit (week 26)
Time above Range (TAR)
Defined as the time (or percentage of measurements) when the glucose value in the interstitial fluid is above 10.0 mmol/L. Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in % or in hours and minutes).
Measured: Last study visit (week 26)
Time below Range (TBR)
Defined as the time (or percentage of measurements) when the glucose value in the interstitial fluid is below 3.9 mmol/L. Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in % or in hours and minutes).
Measured: Last study visit (week 26)
Time above Range (TAR) - Level 1 Hyperglycemia
Defined as the time (or percentage of measurements) when the glucose value in the interstitial fluid is in the range of 10.1-13.9 mmol/L. Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in % or in hours and minutes).
Measured: Last study visit (week 26)
Time above Range (TAR) - Level 2 Hyperglycemia
Defined as the time (or percentage of measurements) when the glucose value in the interstitial fluid is above 13.9 mmol/L. Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in % or in hours and minutes).
Measured: Last study visit (week 26)
Time below Range (TBR) - Level 1 Hypoglycemia
Defined as the time (or percentage of measurements) when the glucose value in the interstitial fluid is in the range of 3.0-3.8 mmol/L. Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in % or in hours and minutes).
Measured: Last study visit (week 26)
Time below Range (TBR) - Level 2 Hypoglycemia
Defined as the time (or percentage of measurements) when the glucose value in the interstitial fluid is below 3.0 mmol/L. Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in % or in hours and minutes).
Measured: Last study visit (week 26)
Time in Tight Range (TITR)
Defined as the time (or percentage of measurements) when the glucose value in the interstitial fluid is in the range of 3.9-7.8 mmol/L. Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in % or in hours and minutes).
Measured: Last study visit (week 26)
Coefficient of variation (CV)
A measure of dynamic glucose variability. Calculated as a ratio of glucose concentration standard deviation and mean glucose concentration, expressed as a percentage. Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in %).
Measured: Last study visit (week 26)
Mean Time in Range (TIR)
Mean Time in Range (TIR) at study visit at week 13 and week 26. Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in % or in hours and minutes).
Measured: Study visit at week 13 and week 26
Mean glucose concentration
Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in mmol/L).
Measured: Last study visit (week 26)
Proportion of participants with Coefficient of variation (CV) below or equal to 36%
Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in %).
Measured: Last study visit (week 26)
Standard deviation of mean glucose concentration
Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in mmol/L).
Measured: Last study visit (week 26)
Proportion of participants with Time in Range (TIR) above 70%
Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in %).
Measured: Last study visit (week 26)
Proportion of participants with Time in Range (TIR) above 90%
Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in %).
Measured: Last study visit (week 26)
Proportion of participants with Glycated hemoglobin (HbA1c) below 6.5%
Assessment by biochemical methods (in %)
Measured: Last study visit (week 26)
Proportion of participants with Glycated hemoglobin (HbA1c) below 5.7%
Assessment by biochemical methods (in %).
Measured: Last study visit (week 26)
Proportion of participants requiring rescue therapy with gliclazide
Measured in %.
Measured: Baseline (week 0) to last study visit (week 26)
Proportion of participants with severe hypoglycemia
Severe hypoglycemia is an epizode of hypoglycemia requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions. Measured in %.
Measured: Baseline (week 0) to last study visit (week 26)
Proportion of participants with severe adverse events
Severe adverse event is defined as symptoms that significantly affects daily activities. Assessment by patients themselves. Measured in %.
Measured: Baseline (week 0) to last study visit (week 26)
Proportion of patients withdrawing from the trial due to adverse events of the interventional drugs
Assessment by patients themselves. Measured in %.
Measured: Baseline (week 0) to last study visit (week 26)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2024
- Study start1 Oct 2024
- Primary completionSep 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 Diabetes Mellitus (T2DM)Studies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06613854
- Sponsor's protocol ID
- E-SEMPA
- Other IDs
- 0120-70/2024-2711-3
- Acronym
- E-SEMPA
- Status last verified
- Apr 2026
- First submitted
- 19 Sep 2024
- Last updated
- 30 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Early Combination Antihyperglycemic Treatment With Metformin and Oral Semaglutide vs. Metformin and Empagliflozin on Glycemic and Metabolic Control in Individuals With Short Duration Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT06613854
- Acronym / sponsor ID
- E-SEMPA / E-SEMPA
- Conditions
- Type 2 Diabetes Mellitus (T2DM)
- Keywords
- E-SEMPA, Early Combination Antihyperglycemic Treatment, Metformin, Semaglutide, Empagliflozin, Glycemic Control, Metabolic Control, Type 2 Diabetes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Study start
- 1 Oct 2024 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 26 Sep 2024 (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 goal of this clinical trial is to learn if early combination with two antidiabetic drugs further improves blood glucose control compared to a single drug regimen in adults with short duration of type 2 diabetes. It will also learn about the effect of the combination treatment on body weight, body composition, blood lipids, oxidative stress, inflammation, metabolic control, insulin resistance and insulin secretion from pancreas, together with its safety profile. The main questions it aims to answer are:
- Does early combination with two antidiabetic drugs improve blood glucose levels, determined by continuous glucose monitoring system?
- Is early combination treatment as safe as treatment with a single antidiabetic drug?
- Does early combination treatment reduces the need for rescue therapy?
- Does early combination treatment reduces body weight and improves body composition?
- Does early combination treatment improves blood lipid parameters, oxidative stress and inflammation?
- Does early combination treatment improves metabolic parameters?
- Does early combination treatment improves insulin resistance and insulin secretion?
Researchers will compare early combination treatment with metformin and either peroral semaglutide or empagliflozin to a single drug regimen with only metformin to see if the combination treatment works to treat type 2 diabetes.
Participants will:
- Take the combination of two antidiabetic drugs or only metformin for every day for 26 weeks.
- Visit the clinic four times during the study duration for checkups and tests.
- Carry a continuous glucose monitoring sensor for 14 days prior to study visits.
Detailed description
Type 2 diabetes (T2D) is a progressive chronic disease and represents a significant risk factor for morbidity and mortality due to cardiovascular disease. In addition to managing glycemia, the use of antihyperglycemic medications with further and independent cardiovascular benefits is recommended in managing individuals with T2D. These medications primarily include sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). Traditionally, treatment of T2D followed a stepwise intensification by adding antihyperglycemic drugs if optimal glycemic control was not achieved. However, current American Diabetes Association guidelines recommend considering early combination therapy at treatment initiation, particularly at high baseline glycated hemoglobin (HbA1c) levels, to shorten the time to achieve glycemic goals.
In everyday clinical practice, however, treatment intensification is often delayed due to clinical inertia, even when glycemic control is suboptimal. Early intensive treatment of T2D has been shown to improve glycemic control, reduce mortality, and lower the risk of both microvascular and macrovascular complications, while also improving the durability of the glycemic effect.
Previous randomized clinical trials on early combination therapy for T2D have primarily focused on glycemic control, as determined by traditional glycemic parameters such as fasting glucose and HbA1c. However, new insights suggest that these measures alone are insufficient for a holistic assessment of glycemic control in diabetes. There is now a recognized need to consider additional indicators of glycemic control, obtained through continuous glucose monitoring (CGM) systems. Furthermore, data are lacking on the direct comparison of the early combination treatment with either SGLT2i or GLP-1RA on top of metformin.
In this 26-week, prospective, open-label, interventional, randomized, single-center clinical trial with a 3-week run-in period, we aim to investigate the effect of early combination treatment with metformin and GLP-1RA or SGLT2i compared to standard monotherapy with metformin and subsequent escalation of antihyperglycemic treatment on glycemic control, as assessed by continuous glucose monitoring systems and HbA1c, body weight, body composition, lipid profile, oxidative stress, inflammation, metabolic control, insulin resistance, and pancreatic beta-cell function in adults with short duration T2D. The primary outcome of the study will be glycemic control, assessed by time in range (TIR).
The study will include individuals of both sexes, of any race or ethnicity, aged between 18 and 70, with a duration of T2D of less than 2 years, HbA1c levels ≤8.0%, on monotherapy with metformin, and naive to treatment with GLP-1RA and SGLT2i.
After the initial 3-week run-in period, patients will be randomized (based on sex, age, and TIR during the run-in period) into three intervention groups in a 1:1:1 ratio:
(i) a control group, continuing metformin monotherapy; (ii) the first study group, receiving metformin and oral semaglutide; and (iii) the second study group, receiving metformin and empagliflozin.
Patients will then be monitored approximately every 13 weeks (3 months) up to 26 weeks (6 months). Prior to randomization, participants will receive a study package containing 3 sensors and 1 reader of the CGM system. The first sensor will be placed on the participants at the start of the run-in period, and subsequent sensors will be self-applied by participants at least 14 days before the last two study visits (at week 13 and week 26).
At each study visit, a review of medical records, a clinical examination, and blood collection for laboratory tests will be conducted. At randomization (week 0) and during the final study visit (week 26), all participants will undergo a modified oral glucose tolerance test (mOGTT) to assess insulin resistance and pancreatic beta-cell function. Additionally, the first 20 participants from each intervention group will undergo whole-body imaging to evaluate body composition. In the case of inadequately controlled glycemia, rescue treatment with gliclazide from the sulfonylurea class will be initiated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Oral Semaglutide Arm | Active comparator | Drug: Oral semaglutideParticipants will receive oral semaglutide in addition to metformin (in a steady daily dose of ≥1500 mg), starting with an initial dose of 3 mg. The dose of semaglutide will be increased to 7 mg after 30 days, and then to a maintenance dose of 14 mg once daily after another 30 days that will be continued to week 26. In the case of inadequately controlled glycemia (HbA1c >8.0 % or symptomatic hyperglycemia), rescue treatment with gliclazide will be initiated. |
| Empagliflozin Arm | Active comparator | Drug: Empagliflozin 10 mgParticipants will receive oral empagliflozin in a once daily dose of 10 mg in addition to metformin (in a steady daily dose of ≥1500 mg). The dose of empagliflozin will not be subsequently changed during the duration of the study. In the case of inadequately controlled glycemia (HbA1c >8.0 % or symptomatic hyperglycemia), rescue treatment with gliclazide will be initiated. |
| Control Arm | No intervention | –Participants will receive metformin in a steady daily dose of ≥1500 mg. In the case of inadequately controlled glycemia (HbA1c >8.0 % or symptomatic hyperglycemia), rescue treatment with gliclazide will be initiated. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosed with type 2 diabetes for up to 2 years (prior to randomization);
- Aged between 18 and 70 years, both sexes, of any race or ethnicity;
- HbA1c ≤8.0% at randomization;
- Baseline treatment with metformin at a steady daily dose of ≥1500 mg;
- Signed informed consent to participate in the study.
Key exclusion criteria (23 listed)
- Treatment at any time in the past with SGLT2i, GLP-1RA, or DPP-4 inhibitors;
- Insulin treatment for longer than 2 weeks in the past;
- Body Mass Index below 22 kg/m2 or BMI above 40 kg/m2;
- Chronic kidney disease stages 3-5 (eGFR below 60 ml/min or the presence of albuminuria (urine albumin-to-creatinine ratio above 34 g/mmol);
- Known cardiovascular disease (angina pectoris, history of myocardial infarction, ischemic heart disease, heart failure, known carotid atherosclerosis, objectively proven peripheral arterial disease, or other known atherosclerotic disease at other locations);
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 |
|---|---|---|
| Oral semaglutideAlso: RybelsusSemaglutide Oral Tablets will be introduced to the Oral Semaglutide Arm as per protocol for regular therapy introduction. | Drug | Oral Semaglutide Arm |
| Empagliflozin 10 mgAlso: JardianceEmpagliflozin Oral Tablets will be introduced to the Empagliflozin Arm as per protocol for regular therapy introduction. | Drug | Empagliflozin Arm |
Primary outcome
Time in Range (TIR)
Time frame: Period of 14 days prior to last study visit (week 26)
Defined as the time (or percentage of measurements) when the glucose value in the interstitial fluid is in the range of 3.9-10.0 mmol/L. Assesment by Continuous Glucose Monitoring system FreeStyle Libre 2 (in % or in hours and minutes).
22 secondary outcomes
Absolute Change in Time in Range (TIR)
Time frame: Baseline (week 0) and last study visit (week 26)
Absolute Change in Glycated hemoglobin (HbA1c)
Time frame: Baseline (week 0) and last study visit (week 26)
Time above Range (TAR)
Time frame: Last study visit (week 26)
Time below Range (TBR)
Time frame: Last study visit (week 26)
Time above Range (TAR) - Level 1 Hyperglycemia
Time frame: Last study visit (week 26)
Time above Range (TAR) - Level 2 Hyperglycemia
Time frame: Last study visit (week 26)
Time below Range (TBR) - Level 1 Hypoglycemia
Time frame: Last study visit (week 26)
Time below Range (TBR) - Level 2 Hypoglycemia
Time frame: Last study visit (week 26)
Time in Tight Range (TITR)
Time frame: Last study visit (week 26)
Coefficient of variation (CV)
Time frame: Last study visit (week 26)
Mean Time in Range (TIR)
Time frame: Study visit at week 13 and week 26
Mean glucose concentration
Time frame: Last study visit (week 26)
Proportion of participants with Coefficient of variation (CV) below or equal to 36%
Time frame: Last study visit (week 26)
Standard deviation of mean glucose concentration
Time frame: Last study visit (week 26)
Proportion of participants with Time in Range (TIR) above 70%
Time frame: Last study visit (week 26)
Proportion of participants with Time in Range (TIR) above 90%
Time frame: Last study visit (week 26)
Proportion of participants with Glycated hemoglobin (HbA1c) below 6.5%
Time frame: Last study visit (week 26)
Proportion of participants with Glycated hemoglobin (HbA1c) below 5.7%
Time frame: Last study visit (week 26)
Proportion of participants requiring rescue therapy with gliclazide
Time frame: Baseline (week 0) to last study visit (week 26)
Proportion of participants with severe hypoglycemia
Time frame: Baseline (week 0) to last study visit (week 26)
Proportion of participants with severe adverse events
Time frame: Baseline (week 0) to last study visit (week 26)
Proportion of patients withdrawing from the trial due to adverse events of the interventional drugs
Time frame: Baseline (week 0) to last study visit (week 26)
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 30 Apr 2026.
- Individual participant dataSharing planned: No
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Active, not recruitingObservational study
An Observational Study to Learn More About How Safe Finerenone is and How Well it Works in Indian People With Chronic Kidney Disease and Type 2 Diabetes in Routine Medical Practice
Chronic Kidney Disease, Type 2 Diabetes Mellitus
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.
University Medical Centre Ljubljana, Diabetes Outpatient Clinic
Ljubljana, Slovenia
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 Oral semaglutide and Empagliflozin 10 mg in people with Type 2 Diabetes Mellitus (T2DM), 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 5 inclusion and 23 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 30 Apr 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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time in Range (TIR) (time frame: Period of 14 days prior to last study visit (week 26)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Apr 2026.