Effect of Early Combination Antihyperglycemic Treatment on Metabolic Control in Individuals With Type 2 Diabetes

NCT06613854 | Recruiting Phase 4

• 2 other identifiers: E-SEMPA0120-70/2024-2711-3
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Type 2 Diabetes Mellitus (T2DM)

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

Outcome Measures

Primary Outcomes (1)

• 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).

  Period of 14 days prior to last study visit (week 26)

Secondary Outcomes (22)

• Absolute Change in Time in Range (TIR)

  Baseline (week 0) and last study visit (week 26)

• Absolute Change in Glycated hemoglobin (HbA1c)

  Baseline (week 0) and last study visit (week 26)

• Time above Range (TAR)

  Last study visit (week 26)

• Time below Range (TBR)

  Last study visit (week 26)

• Time above Range (TAR) - Level 1 Hyperglycemia

  Last study visit (week 26)

Other Outcomes (40)

• Change in Body Weight

  Baseline (week 0) and last study visit (week 26)

• Proportion of participants with a reduction of Body Weight above or equal to 5%

  Baseline (week 0) and last study visit (week 26)

• Proportion of participants with a reduction of Body Weight above or equal to 10%

  Baseline (week 0) and last study visit (week 26)

Study Arms (3)

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.

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.

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.

Interventions

Oral semaglutide DRUG

Semaglutide Oral Tablets will be introduced to the Oral Semaglutide Arm as per protocol for regular therapy introduction.

Also known as: Rybelsus

Oral Semaglutide Arm

Empagliflozin 10 mg DRUG

Empagliflozin Oral Tablets will be introduced to the Empagliflozin Arm as per protocol for regular therapy introduction.

Also known as: Jardiance

Empagliflozin Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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);
• 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;

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Study Sites (1)

University Medical Centre Ljubljana, Diabetes Outpatient Clinic

Ljubljana, 1000, Slovenia

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

semaglutide; empagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2024
• First Posted: September 26, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)