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

NCT ID: NCT06054035

Last Updated: 2025-07-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

170 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-26

Study Completion Date

2027-09-30

Brief Summary

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More than 50% of patients with type 2 diabetes develop micro- and/or macrovascular complications during the course of the disease. Additionally, many patients at risk for diabetes develop metabolically driven complications including kidney and heart disease. Thus, it is of utmost importance to improve prevention of T2D and with this complications. Remission of prediabetes, i.e. normalization of hyperglycemia by means of lifestyle intervention is one of the most effective ways to prevent the development of T2D and complications. Novel sub-phenotyping analysis identified clusters of risk for diabetes associated with different complications, opening opportunities to new therapeutic approaches, despite and in addition to lifestyle changes. So far, pharmacological therapy is not indicated for patients with prediabetes. Remission of hyperglycemia associated with prediabetes during lifestyle interventions not only prevents T2D but is also linked with reduced albuminuria and lower microvascular and kidney complications. Thus, reaching normoglycemia (i.e. prediabetes remission) is important for reducing the risk of (pre-)diabetes-associated complications including micro- and even macrovascular disease. In patients with T2D, recent data show that dapagliflozin can improve diabetes remission, and thus, likely complications. However, to date no data have assessed whether or not this is also true in patients with hyperglycemia related to prediabetes which, as outlined above, already causes different complications.

Subphenotyping of patients with newly onset diabetes suggests that for some individuals, it would be too late to start interventions against dagainst complications at the time of diagnosis of type 2 diabetes. Therefore, individuals at elevated risk to develop T2D and complications should receive preventive measures well before the diagnosis of T2D. This study will provide evidence whether such an early intervention contributes to the remission of hyperglycemia related to prediabetes to protect from associated complications such as renal disease. The studied population will comprise individuals who have hyperglycemia in the range of prediabetes and are thus prone to not only develop T2D, but also early nephropathy but in clinical practice do not receive medical treatment due to the early stage of the disease. These subjects will receive Dapagliflozin 10 mg or Placebo for 6 months. The placebo treatment arm reflects current practice. In order guarantee a benefit the patients in the placebo arm will receive a lifestyle intervention.

Detailed Description

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Conditions

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Type2diabetes PreDiabetes Renal Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomization will be performed stratified by prediabetes cluster.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Dapagliflozin (Forxiga®) and lifestyle counselling

Group Type EXPERIMENTAL

Dapagliflozin (Forxiga®)

Intervention Type DRUG

Dapagliflozin 10 mg once daily for 6 months. Route of administration: oral.

Lifestyle Intervention

Intervention Type BEHAVIORAL

Patients receive a conventional lifestyle intervention (one in depth individual session at the beginning and standard care information on a healthy lifestyle at every visit thereafter).

Placebo matching Dapaglifolzin and lifestyle counselling

Group Type PLACEBO_COMPARATOR

Placebo matching Dapaglifolzin

Intervention Type DRUG

Placebo matching Dapaglifolzin once daily for 6 months. Route of administration: oral.

Lifestyle Intervention

Intervention Type BEHAVIORAL

Patients receive a conventional lifestyle intervention (one in depth individual session at the beginning and standard care information on a healthy lifestyle at every visit thereafter).

Interventions

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Dapagliflozin (Forxiga®)

Dapagliflozin 10 mg once daily for 6 months. Route of administration: oral.

Intervention Type DRUG

Placebo matching Dapaglifolzin

Placebo matching Dapaglifolzin once daily for 6 months. Route of administration: oral.

Intervention Type DRUG

Lifestyle Intervention

Patients receive a conventional lifestyle intervention (one in depth individual session at the beginning and standard care information on a healthy lifestyle at every visit thereafter).

Intervention Type BEHAVIORAL

Eligibility Criteria

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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
Minimum Eligible Age

35 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role collaborator

German Center for Diabetes Research

OTHER

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role collaborator

University Hospital Tuebingen

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Charité Universitätsmedizin Berlin, Klinik für Endokrinologie und Stoffwechselmedizin

Berlin, , Germany

Site Status RECRUITING

Universitätsstudienzentrum für Stoffwechselerkrankungen , Medizinische Klinik und Poliklinik III

Dresden, , Germany

Site Status RECRUITING

German Diabetes Center, Leibniz-Center for Diabetes Research at the Heinrich-Heine-University Duesseldorf

Düsseldorf, , Germany

Site Status RECRUITING

Heidelberg University Hospital - Department of Endocrinology and Metabolism

Heidelberg, , Germany

Site Status RECRUITING

Medizinische Klinik und Poliklinik III - Bereich Endokrinologie

Leipzig, , Germany

Site Status RECRUITING

Medizinische Klinik I, UKSH Campus LübeckAG Meyhöfer - Endocrinology, Diabetes & Metabolism

Lübeck, , Germany

Site Status NOT_YET_RECRUITING

Diabetes Center Med. Klinik und Poliklinik IV, Klinikum der Universität München, LMU

München, , Germany

Site Status RECRUITING

Institut für Ernährungsmedizin, Technische Universität München

München, , Germany

Site Status NOT_YET_RECRUITING

University Hospital Tuebingen, Otfried-Mueller Str. 10

Tübingen, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Andreas Birkenfeld, Prof. Dr.

Role: CONTACT

0049707129 ext. 83670

Andreas Fritsche, Prof. Dr.

Role: CONTACT

0049707129 ext. 80590

Facility Contacts

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Knut Mai, Prof. Dr. med.

Role: primary

+49 30 450 514 252

Nikolaos Perakakis, Prof. Dr. med.

Role: primary

Robert Wagner, Prof. Dr. med.

Role: primary

Julia Szendrödi, Prof. Dr. med.

Role: primary

Matthias Blüher, Prof. Dr.

Role: primary

+49 341 97 22901

Svenja Meyhöfer, PD Dr.

Role: primary

+49 451 3101 7827

Jochen Seißler, Prof. Dr. med.

Role: primary

(+89) 4400 5220

Hans Hauner, Prof. Dr. med.

Role: primary

+498928924921

Andreas Birkenfeld, Prof. Dr.

Role: primary

+49 (0)7071 29 80662

Other Identifiers

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LIFETIME

Identifier Type: -

Identifier Source: org_study_id

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