SGLT2 Inhibition in Addition to Lifestyle Intervention and Risk for Complications in Subtypes of Patients With Prediabetes

Launched by UNIVERSITY HOSPITAL TUEBINGEN · Sep 18, 2023

Keywords

ClinConnect Summary

This clinical trial is studying whether a medication called Dapagliflozin can help prevent kidney issues in people who are at high risk for developing type 2 diabetes and already show early signs of kidney disease. The trial aims to find out if starting treatment early—before the full diagnosis of diabetes—is beneficial in preserving kidney function. Participants will either receive Dapagliflozin or a placebo (which means they won't be getting the active medication) for two years, along with lifestyle interventions like diet and exercise guidance, which are standard practices for managing health.

To be eligible for the trial, participants need to be between the ages of 35 and 75, have prediabetes (which means their blood sugar levels are higher than normal but not yet in the diabetes range), and show early signs of kidney issues. Individuals with existing diabetes or significant kidney problems will not be included. Participants can expect regular check-ups and monitoring throughout the study to ensure their safety and the effectiveness of the treatment. This trial is important as it may open new pathways for early intervention in people at risk of diabetes and kidney complications.

Gender

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Eligibility criteria

• Inclusion Criteria:
• • 1. Male, female or diverse patients aged between 35 and 75 years (including)
• • 2. Patients assigned to high risk for diabetes clusters 3, 5 and 6 according to (Wagner et al., 2021) who have signs of early kidney disease (urinary albumin-to-creatinine ratio (uACR) 30mg/g - 300 mg/g, CKD stage G1A2 or G2A2)
• • 3. Prediabetes (defined by one of the following: FG \> 100 mg/dL, HbA1c \> 5,6 or 2h OGTT glucose \> 140 mg/dL)
• • 4. BMI ≥20 kg/m2
• • 5. TSH within normal range
• • 6. Ability to understand and follow study-related instructions
• • 7. Negative pregnancy test for premenopausal women (blood or urine)
• • 8. Patients who are receiving thyroid replacement therapy must be on a stable treatment regimen for at least 3 months prior to the screening visit (V0)
• • 9. 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 (V0)
• • 10. Patients who are treated antihypertensive medication such as ACE inhibitors and AT1 receptor antagonists, thiazides as well as loop diuretics must be on stable treatment for at least 2 weeks
• • 11. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures.
• • 12. 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 intake of antidepressant or antipsychotic agents
• • 21. Positive Screening for a moderate/severe depression (BDI ≥29)
• • 22. history of hypersensitivity to the study drug or its ingredients
• • 23. allergy to iodine contrast dye
• • 24. more than 5% weight loss in the last 3 months
• • 25. Pregnant or breastfeeding women
• • 26. Subject (male, female or diverse) 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).
• • 27. 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.
• • 28. Current participation in other interventional clinical trials or treatment with other IMPs within five times the half-life of the drug
• • 29. Previous therapy with dapagliflozin or other drugs that can potentially lead to overlapping toxicities within five times the half-life of the drug
• • 30. Patients who do not want to be informed about accidental findings
• • 31. Any other clinical condition that would jeopardize subjects' safety or well-being while participating in this clinical trial
• • 32. 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