Type2diabetesPhase 4NCT06054035
SGLT2 Inhibition in Addition to Lifestyle Intervention and Risk for Complications in Subtypes of Patients With Prediabetes
A Phase 4 study testing Dapagliflozin (Forxiga®) and Lifestyle Intervention in people with Type2diabetes and PreDiabetes, run by University Hospital Tuebingen at 9 sites in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Type2diabetes, PreDiabetes, Renal Failure
- What is being tested?
- Dapagliflozin (Forxiga®) and Lifestyle Intervention
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 170 participants
- Where
- 9 sitesGermany
- Study dates
- 26 Oct 2023to 30 Sep 2027
- Phase
- Phase 4
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 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male, female or intersexualpatients aged between 35 and 75 years (including)
- Prediabetes (defined by one of the following: FG ≥ 100 mg/dL or 2h OGTT glucose ≥ 140 mg/dL)
- BMI ≥20 kg/m2
- TSH within normal range
- Ability to understand and follow study-related instructions
- Negative pregnancy test for premenopausal women (blood)
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- 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)
- 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)
- 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
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures.
- 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
Who cannot join
- Manifest diabetes mellitus
- eGFR (as calculated by the CKD-EPI equation) < 60 ml/min/1.73 m2
- all glucose altering medications (including current therapy with dapagliflozin or empagliflozin or any other SGLT2-Inhibitor)
- Symptomatic chronic congestive heart disease
- New diuretic or antihypertensive medication or dosing changes within the last 2 weeks, for aldosterone antagonists within the last 6 weeks
- known or suspected orthostatic proteinuria
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- 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
- history of or current therapy for congestive heart failure (NYHA III and IV), pacemaker or aortic stenosis > II°
- acute pancreatic disease (i.e. elevated lipase 3x ULN)
- rapidly progressing renal disease or anuria
- known HIV infection or positive HIV test at screening
- history of or planned organ transplantation
- 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
- 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).
- treatment with glucocorticoids
- antibiotic treatment within the last 4 weeks
- History of ketoacidosis
- history of repeated urogenital infection
- hemoglobinopathies, haemolytic anaemia, or chronic anaemia (haemoglobin concentration <12.0 g/dL)
- presence of psychiatric disorder or new intake of antidepressant or antipsychotic agents(start within last 3 months)
- Positive Screening for a severe depression (BDI ≥29)
- history of hypersensitivity to the study drug or its ingredients
- more than 5% weight loss in the last 3 months
- Pregnant or breastfeeding women
- 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.
- Current participation in other interventional clinical trials or treatment with other IMPs within five times the half-life of the drug
- Previous therapy with dapagliflozin or other drugs that can potentially lead to overlapping toxicities within five times the half-life of the drug
- Patients who do not want to be informed about accidental findings
- Any other clinical condition that would jeopardize subjects' safety or well-being while participating in this clinical trial
- 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
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
Germany9 sites, 9 recruiting
- Recruiting
Charité Universitätsmedizin Berlin, Klinik für Endokrinologie und Stoffwechselmedizin
Berlin
Knut Mai, Prof. Dr. med., +49 30 450 514 252, knut.mai@charite.de
- Recruiting
Universitätsstudienzentrum für Stoffwechselerkrankungen , Medizinische Klinik und Poliklinik III
Dresden
Nikolaos Perakakis, Prof. Dr. med., +49 351 458-13651, Nikolaos.Perakakis@ uniklinikum-dresden.de
- Recruiting
German Diabetes Center, Leibniz-Center for Diabetes Research at the Heinrich-Heine-University Duesseldorf
Düsseldorf, 40225
Robert Wagner, Prof. Dr. med.
- Recruiting
Heidelberg University Hospital - Department of Endocrinology and Metabolism
Heidelberg, 69120
Julia Szendrödi, Prof. Dr. med.
- Recruiting
Medizinische Klinik und Poliklinik III - Bereich Endokrinologie
Leipzig
Matthias Blüher, Prof. Dr., +49 341 97 22901, Matthias.Blueher@medizin.uni-leipzig.de
- Recruiting
Medizinische Klinik I, UKSH Campus LübeckAG Meyhöfer - Endocrinology, Diabetes & Metabolism
Lübeck, 23562
Svenja Meyhöfer, PD Dr., +49 451 3101 7827, svenja.meyhoefer@uni-luebeck.de
- Recruiting
Diabetes Center Med. Klinik und Poliklinik IV, Klinikum der Universität München, LMU
München
Jochen Seißler, Prof. Dr. med., (+89) 4400 5220, jochen.seissler@med.un-muenchen.de
- Recruiting
Institut für Ernährungsmedizin, Technische Universität München
München
Katharina Timper, Prof. Dr. med., +498928924912, Katharina.Timper@mri.tum.de
- Recruiting
University Hospital Tuebingen, Otfried-Mueller Str. 10
Tübingen, 72076
Andreas Birkenfeld, Prof. Dr., +49 (0)7071 29 80662, andreas.birkenfeld@med.uni-tuebingen.de
About this study
Official title: SGLT2 Inhibition in Addition to Lifestyle Intervention and Risk for Complications in Subtypes of Patients With Prediabetes - a Randomized, Placebo Controlled, Multi-center Trial
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.
- Conditions
- Type2diabetes, PreDiabetes, Renal Failure
- Being tested
- Dapagliflozin (Forxiga®), Placebo matching Dapaglifolzin, Lifestyle Intervention
- Medical subject headings
- Prediabetic State, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin (Forxiga®)Drug
Dapagliflozin 10 mg once daily for 6 months. Route of administration: oral.
Placebo matching DapaglifolzinDrug
Placebo matching Dapaglifolzin once daily for 6 months. Route of administration: oral.
Lifestyle InterventionBehavioural
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).
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin (Forxiga®) and lifestyle counselling | Experimental | Not described Receives: Drug: Dapagliflozin (Forxiga®); Behavioral: Lifestyle Intervention |
| Placebo matching Dapaglifolzin and lifestyle counselling | Placebo comparator | Not described Receives: Drug: Placebo matching Dapaglifolzin; Behavioral: Lifestyle Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of remission of hyperglycemia
Frequency of individuals with prediabetes remission (normalization of fasting and 2h glucose concentrations) with dapagliflozin in comparison to treatment with placebo.
Measured: 6 months
Secondary outcomes (5)
Reduction of urinary albumine-creatinine ratio.
To test differences between the two treatment arms for reduction of urinary albumine-creatinine ratio.
Measured: 1 month throuhg 6 months
Change in estimated glomerular filtration rate (eGFR)
To test differences between the two treatment arms for reduction in estimated glomerular filtration rate (eGFR).
Measured: 7 months
Slopes over time of estimated glomerular filtration rate (eGFR).
To test differences between the two treatment arms for slopes over time of estimated glomerular filtration rate (eGFR).
Measured: baseline to 4 weeks, baseline to 7 months, 3 months to 7 months, baseline to 12 months
Numbers of patients showing resolution of chronic kidney disease (CKD)
To test differences between the two treatment arms for resolution of chronic kidney disease (CKD) for at least 3 months continuously: Urine Albumin Creatinin Ratio (uACR) < 30mg/g
Measured: 3 months through 12 months
Prediabetes remission maintenance
Effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on remission of prediabetes as defined in the oGTT a fasting glucose <100 mg/dl and 2 h glucose <140 mg/dl at follow up
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2023
- Study start26 Oct 2023
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type2diabetesStudies of the same condition, open and under way.
- 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
- Model description
- Randomization will be performed stratified by prediabetes cluster.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 170 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Collaborators
- German Federal Ministry of Education and Research, German Center for Diabetes Research, AstraZeneca
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06054035
- Sponsor's protocol ID
- LIFETIME
- Status last verified
- Sep 2026
- First submitted
- 6 Sep 2023
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No