Using SGLT2 inhibitors with lifestyle changes to prevent complications in prediabetes patients

SGLT2 Inhibition in Addition to Lifestyle Intervention and Risk for Complications in Subtypes of Patients With Prediabetes - a Randomized, Placebo Controlled, Multi-center Trial

This study is testing if a diabetes medication combined with lifestyle changes can help people with prediabetes and early kidney problems avoid serious health issues.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 170 (estimated)
• Ages: 35 Years to 75 Years
• Sex: All
• Sponsor: University Hospital Tuebingen (Academic / other)
• Locations: 9 sites (Berlin and 8 other locations)
• Trial ID: NCT06054035 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effects of SGLT2 inhibitors, specifically Dapagliflozin, in conjunction with lifestyle interventions on patients with prediabetes and early signs of kidney disease. The study focuses on individuals identified as high risk for diabetes complications, aiming to assess whether this combination can reduce the progression of kidney and cardiovascular issues. Participants will be monitored for changes in their health status, particularly concerning kidney function and metabolic health. The trial seeks to provide prospective data on the efficacy of pharmacological therapy in a population that currently lacks such treatment options.

Who should consider this trial

Good fit: Ideal candidates are adults aged 35 to 75 with prediabetes and early kidney disease, specifically those with a urinary albumin-to-creatinine ratio indicating early chronic kidney disease.

Not a fit: Patients without prediabetes or those with advanced chronic kidney disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the risk of developing diabetes-related complications in patients with prediabetes.

How similar studies have performed: While SGLT2 inhibitors have shown success in treating diabetes and related complications, this specific application in prediabetes is novel and has not been extensively tested.

Eligibility criteria

Inclusion criteria:

1. Male, female or intersexualpatients aged between 35 and 75 years (including)
2. Prediabetes (defined by one of the following: FG ≥ 100 mg/dL or 2h OGTT glucose ≥ 140 mg/dL)
3. BMI ≥20 kg/m2
4. TSH within normal range
5. Ability to understand and follow study-related instructions
6. Negative pregnancy test for premenopausal women (blood)
7. Patients who are receiving thyroid replacement therapy must be on a stable treatment regimen for at least 3 months prior to the screening visit (V-1)
8. Patients who are receiving antihypertensive medication such as mineralocorticoid receptor antagonists must be on a stable treatment regimen for at least 6 weeks prior to the screening visit (V-1)
9. Patients who are treated antihypertensive medication such as ACE inhibitors and AT1receptor antagonists, thiazides as well as loop diuretics must be on stable treatment for at least 2 weeks
10. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures.
11. Patients will not be included in the study if, in the opinion of the investigator participation will lead to an unacceptable risk to the subjects' safety or well-being

Exclusion Criteria

1. Manifest diabetes mellitus
2. eGFR (as calculated by the CKD-EPI equation) \< 60 ml/min/1.73 m2
3. all glucose altering medications (including current therapy with dapagliflozin or empagliflozin or any other SGLT2-Inhibitor)
4. Symptomatic chronic congestive heart disease
5. New diuretic or antihypertensive medication or dosing changes within the last 2 weeks, for aldosterone antagonists within the last 6 weeks
6. known or suspected orthostatic proteinuria
7. any acute severe or chronic severe illness, including the following: malignant disease ongoing or \< 5 years ago, unstable cardiovascular disease or procedure within 3 months prior to enrolment or expected to require coronary revascularisation procedure
8. history of or current therapy for congestive heart failure (NYHA III and IV), pacemaker or aortic stenosis \> II°
9. acute pancreatic disease (i.e. elevated lipase 3x ULN)
10. rapidly progressing renal disease or anuria
11. known HIV infection or positive HIV test at screening
12. history of or planned organ transplantation
13. history or presence of inflammatory bowel disease or other severe gastrointestinal diseases, particularly those which may impact gastric emptying, such as gastroparesis or pyloric stenosis
14. relevant hepatic disease, including, but not limited to, acute hepatitis, chronic active hepatitis, or severe hepatic insufficiency, including patients with alanine aminotransferase and/or aspartate aminotransferase \> 3 x upper limit of normal and/or total bilirubin (TB) \> 2 mg/dL (\> 34.2 μmol/L) (patients with TB \> 2 mg/dL \[\> 34.2 μmol/L\] and documented Gilbert's syndrome will be allowed to participate).
15. treatment with glucocorticoids
16. antibiotic treatment within the last 4 weeks
17. History of ketoacidosis
18. history of repeated urogenital infection
19. hemoglobinopathies, haemolytic anaemia, or chronic anaemia (haemoglobin concentration \<12.0 g/dL)
20. presence of psychiatric disorder or new intake of antidepressant or antipsychotic agents(start within last 3 months)
21. Positive Screening for a severe depression (BDI ≥29)
22. history of hypersensitivity to the study drug or its ingredients
23. more than 5% weight loss in the last 3 months
24. Pregnant or breastfeeding women
25. Subject (male, female or intersexual) is not willing to use highly effective contraceptive methods during treatment and for 14 days (male or female) after the end of treatment (highly effective methods are defined as: combined hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence).

    Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the trial participant and that the vasectomized partner has received medical assessment of the surgical success.
26. Current participation in other interventional clinical trials or treatment with other IMPs within five times the half-life of the drug
27. Previous therapy with dapagliflozin or other drugs that can potentially lead to overlapping toxicities within five times the half-life of the drug
28. Patients who do not want to be informed about accidental findings
29. Any other clinical condition that would jeopardize subjects' safety or well-being while participating in this clinical trial
30. Patients will not be included in the study if, in the opinion of the investigator, participation leads to an unacceptable risk to their safety and well-being

Where this trial is running

Berlin and 8 other locations

• Charité Universitätsmedizin Berlin, Klinik für Endokrinologie und Stoffwechselmedizin — Berlin, Germany (Recruiting)
• Universitätsstudienzentrum für Stoffwechselerkrankungen , Medizinische Klinik und Poliklinik III — Dresden, Germany (Recruiting)
• German Diabetes Center, Leibniz-Center for Diabetes Research at the Heinrich-Heine-University Duesseldorf — Düsseldorf, Germany (Recruiting)
• Heidelberg University Hospital - Department of Endocrinology and Metabolism — Heidelberg, Germany (Recruiting)
• Medizinische Klinik und Poliklinik III - Bereich Endokrinologie — Leipzig, Germany (Recruiting)
• Medizinische Klinik I, UKSH Campus LübeckAG Meyhöfer - Endocrinology, Diabetes & Metabolism — Lübeck, Germany (Not_yet_recruiting)
• Diabetes Center Med. Klinik und Poliklinik IV, Klinikum der Universität München, LMU — München, Germany (Recruiting)
• Institut für Ernährungsmedizin, Technische Universität München — München, Germany (Not_yet_recruiting)
• University Hospital Tuebingen, Otfried-Mueller Str. 10 — Tübingen, Germany (Recruiting)

Study contacts

• Study coordinator: Andreas Birkenfeld, Prof. Dr.

Conditions Type2diabetes; PreDiabetes; Renal Failure