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

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.

Study Overview

• Status: Recruiting
• Conditions: Renal Failure; PreDiabetes; Type2diabetes
• Intervention / Treatment: Behavioral: Lifestyle Intervention; Drug: Dapagliflozin (Forxiga®); Drug: Placebo matching Dapaglifolzin

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Andreas Birkenfeld, Prof. Dr.; Phone Number: 83670 0049707129; Email: andreas.birkenfeld@med.uni-tuebingen.de
• Study Contact Backup: Name: Andreas Fritsche, Prof. Dr.; Phone Number: 80590 0049707129; Email: andreas.fritsche@med.uni-tuebingen.de

Study Locations

• Germany
  • Berlin, Germany
    • Recruiting
    • Charité Universitätsmedizin Berlin, Klinik für Endokrinologie und Stoffwechselmedizin
    • Contact: Knut Mai, Prof. Dr. med.; Phone Number: +49 30 450 514 252; Email: knut.mai@charite.de
  • Dresden, Germany
    • Recruiting
    • Universitätsstudienzentrum für Stoffwechselerkrankungen , Medizinische Klinik und Poliklinik III
    • Contact: Nikolaos Perakakis, Prof. Dr. med.; Phone Number: +49 351 458-13651; Email: Nikolaos.Perakakis@ uniklinikum-dresden.de
  • Duesseldorf, Germany, 40225
    • Recruiting
    • German Diabetes Center, Leibniz-Center for Diabetes Research at the Heinrich-Heine-University Duesseldorf
    • Contact: Robert Wagner, Prof. Dr. med.
  • Heidelberg, Germany, 69120
    • Recruiting
    • Heidelberg University Hospital - Department of Endocrinology and Metabolism
    • Contact: Julia Szendrödi, Prof. Dr. med.
  • Leipzig, Germany
    • Recruiting
    • Medizinische Klinik und Poliklinik III - Bereich Endokrinologie
    • Contact: Matthias Blüher, Prof. Dr.; Phone Number: +49 341 97 22901; Email: Matthias.Blueher@medizin.uni-leipzig.de
  • Lübeck, Germany, 23562
    • Not yet recruiting
    • Medizinische Klinik I, UKSH Campus LübeckAG Meyhöfer - Endocrinology, Diabetes & Metabolism
    • Contact: Svenja Meyhöfer, PD Dr.; Phone Number: +49 451 3101 7827; Email: svenja.meyhoefer@uni-luebeck.de
  • München, Germany
    • Recruiting
    • Diabetes Center Med. Klinik und Poliklinik IV, Klinikum der Universität München, LMU
    • Contact: Jochen Seißler, Prof. Dr. med.; Phone Number: (+89) 4400 5220; Email: jochen.seissler@med.un-muenchen.de
  • München, Germany
    • Not yet recruiting
    • Institut für Ernährungsmedizin, Technische Universität München
    • Contact: Hans Hauner, Prof. Dr. med.; Phone Number: +498928924921; Email: hans.hauner@tum.de
  • Tuebingen, Germany, 72076
    • Recruiting
    • University Hospital Tuebingen, Otfried-Mueller Str. 10
    • Contact: Andreas Birkenfeld, Prof. Dr.; Phone Number: +49 (0)7071 29 80662; Email: andreas.birkenfeld@med.uni-tuebingen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin (Forxiga®) and lifestyle counselling	Behavioral: 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).; Drug: Dapagliflozin (Forxiga®); Dapagliflozin 10 mg once daily for 6 months. Route of administration: oral.
Placebo Comparator: Placebo matching Dapaglifolzin and lifestyle counselling	Behavioral: 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).; Drug: Placebo matching Dapaglifolzin; Placebo matching Dapaglifolzin once daily for 6 months. Route of administration: oral.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of urinary albumine-creatinine ratio.	To test differences between the two treatment arms for reduction of urinary albumine-creatinine ratio.	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).	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).	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	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	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity	Baseline-adjusted insulin sensitivity at EoT using Insulin sensitivity: ISI-Matsuda/Oral glucose insulin sensitivity index.	6 months, 12 months
Insulin secretion	Baseline-adjusted insulin secretion at EoT using an estimate for insulin secretion: C-peptide0-30AUC/glucose0-30AUC.	6 months, 12 months
Number of patients progressing to Type 2 Diabetes	Effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on the progression to T2DM as defined as a HbA1c ≥ 6.5	6 months, 12 months
Change in body weight	Effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on change in body weight.	6 months, 12 months
Change in BMI	Effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on BMI.	6 months, 12 months
Change in whole body fat	Effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on whole body fat measures by magnetic resonance imaging.	6 months, 12 months
Change in visceral fat	Effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on visceral fat measures by magnetic resonance imaging.	6 months, 12 months
Change in liver fat	Effects of 6 months reatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on liver fat measures by magnetic resonance spectroscopy.	6 months, 12 months
Change in subcutaneous fat	Effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on subcutaneous fat measures by magnetic resonance imaging.	6 months, 12 months
Arterial blood pressure	Baseline-adjusted arterial blood pressure at EoT	6 months, 7 months, 12 months
New onset or progress of neuropathy	Effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on new onset or progress of and neuropathy assessed by using the Rydel-Seiffer tuning fork and a 10 g monofilament	6 months, 12 months
Quality of life using the Short Form Health Survey (SF)-36 questionnaire	Effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on quality of life using the SF-36 questionnaire (scored on a 0 to 100 range; the higher the score, the higher quality of life)	6 months, 12 months
Interaction between diabetes risk cluster and intervention for numbers of patients showing a resolution of Prediabetes	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on remission of prediabetes as defined a fasting glucose <100 mg/dl and 2 h glucose <140 mg/dl in the OGTT.	6 months, 12 months
Interaction between diabetes risk cluster and intervention for change in albuminuria	To test interaction between diabetes risk clusters and intervention for kidney damage as shown by albuminuria in patients with CKD stage G1A2/G2A2 and prediabetes can be improved by a treatment with the SGLT2 inhibitor dapagliflozin (10mg/day) and lifestyle counselling compared to placebo and lifestyle counselling for 6 months calculated as mean of baseline-adjusted uACR measurements with dapagliflozin in comparison to treatment with placebo.	6 months, 12 months
Interaction between diabetes risk cluster and intervention for change in estimated glomerular filtration rate (eGFR).	To test interaction between diabetes risk clusters and intervention on estimated glomerular filtration rate (eGFR).	6 months, 12 months
Interaction between diabetes risk cluster and intervention for slopes over time of estimated glomerular filtration rate (eGFR).	To test interaction between diabetes risk clusters and intervention on slopes over time of estimated glomerular filtration rate (eGFR).	4 weeks, 3 months, 6 months, 7 months, 12 months
Interaction between diabetes risk cluster and intervention for numbers of patients showing resolution of chronic kidney disease (CKD)	To test interaction between diabetes risk clusters and intervention for resolution of chronic kidney disease (CKD) for at least 3 months continuously: Urine Albumin Creatinin Ratio (uACR) < 30mg/g	3 months, 6 months, 7 months, 12 months
Interaction between diabetes risk cluster and intervention for insulin sensitivity.	To test interaction between diabetes risk clusters and intervention for baseline-adjusted insulin sensitivity at EoT using Insulin sensitivity: ISI-Matsuda/Oral glucose insulin sensitivity index.	6 months, 12 months
Interaction between diabetes risk cluster and intervention for insulin secretion	To test interaction between diabetes risk clusters and intervention for baseline-adjusted insulin secretion at EoT using insulin secretion:C-peptide0-30AUC/glucose0-30AUC.	6 months, 12 months
Interaction between diabetes risk cluster and intervention for number of patients progressing to Type 2 Diabetes	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on the progression to T2DM as defined as a HbA1c ≥ 6.5	6 months, 12 months
Interaction between diabetes risk cluster and intervention for change in body weight	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on change in body weight.	6 months, 12 months
Interaction between diabetes risk cluster and intervention for change in BMI.	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on BMI.	6 months, 12 months
Interaction between diabetes risk cluster and intervention for change in whole body fat	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on whole body fat measures by magnetic resonance imaging.	6 months, 12 months
Interaction between diabetes risk cluster and intervention for change in visceral fat	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on visceral fat measures by magnetic resonance imaging.	6 months, 12 months
Interaction between diabetes risk cluster and intervention for change in liver fat	To test interaction between diabetes risk clusters and intervention for effects effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on liver fat measures by magnetic resonance spectroscopy.	6 months, 12 months
Interaction between diabetes risk cluster and intervention for change in subcutaneous fat	To test interaction between diabetes risk clusters and intervention for effects effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on subcutaneous fat measures by magnetic resonance imaging.	6 months, 12 months
Interaction between diabetes risk cluster and intervention for change in arterial blood pressure	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on the arterial blood pressure	6 months, 7 months, 12 months
Interaction between diabetes risk cluster and intervention on the new onset or progress of neuropathy	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on the new onset or progress of neuropathy assessed by using the Rydel-Seiffer tuning fork and a 10 g monofilament.	6 months, 12 months
Interaction between diabetes risk cluster and intervention for change in quality of life	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on the quality of life using the SF-36 questionnaire (scored on a 0 to 100 range; the higher the score, the higher quality of life).	6 months, 12 months
Small vessel density	Change in small vessel density and junction-to-endpoint branches between baseline and EoT in the dapagliflozin versus placebo group as assessed by optoacustic imagingMyocardial function	6 months, 12 months
Interaction between diabetes risk cluster and intervention on small vessel density	To test interaction between diabetes risk clusters and intervention for change in small vessel density and junction-to-endpoint branches between baseline and EoT in the dapagliflozin versus placebo group as assessed by optoacustic imagingMyocardial function	6 months, 12 months
New onset or progress of diabetic retinopathy	New onset or progress of retinopathy between baseline and EoT in the dapagliflozin versus placebo group. This will be assessed by a grading algorithm using the iCare DRSplus camera. Since macula edema at early stages cannot adequately be assessed with fundus pictures, we will assess maculopathies using optical coherence tomography	6 months, 12 months
Interaction between diabetes risk cluster and intervention on the new onset or progress of diabetic retinopathy	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on the new onset or progress of retinopathy between baseline and EoT in the dapagliflozin versus placebo group. This will be assessed by a grading algorithm using the iCare DRSplus camera. Since macula edema at early stages cannot adequately be assessed with fundus pictures, we will assess maculopathies using optical coherence tomography.	6 months, 12 months
Composition of the gut microbiome	Change in gut microbial community and gene abundances within and between intervention and placebo groups over time using next generation sequencing data and machine learning algorithms	3 months, 6 months, 7 months, 12 months
Interaction between diabetes risk cluster and intervention for composition of the gut microbiome	To test interaction between diabetes risk clusters and intervention change in gut microbial community and gene abundances within and between intervention and placebo groups over time using next generation sequencing data and machine learning algorithms	3 months, 6 months, 7 months, 12 months
Urinary metabolite signature of SGLT2 inhibitors	Changes in urinary metabolites within and between intervention and placebo groups over time using MS-based metabolomics and machine learning algorithms	6 months, 12 months
Interaction between diabetes risk cluster and intervention for urinary metabolite signature of SGLT2 inhibitors	To test interaction between diabetes risk clusters and intervention changes in urinary metabolites within and between intervention and placebo groups over time using MS-based metabolomics and machine learning algorithms	6 months, 12 months
Myocardial function shown by left ventricular mass index	Effects of dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on left ventricular mass index assessed via cardiac magnetic resonance imaging	6 months, 12 months
Interaction between diabetes risk cluster and intervention on Myocardial function shown by left ventricular mass index	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on left ventricular mass index assessed via cardiac magnetic resonance imaging.	6 months, 12 months
Myocardial function shown by systolic myocardial function	Effects of dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on systolic myocardial function assessed via cardiac magnetic resonance imaging.	6 months, 12 months
Interaction between diabetes risk cluster and intervention on Myocardial function shown by systolic myocardial function	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on systolic myocardial function assessed via cardiac magnetic resonance imaging.	6 months, 12 months
Myocardial function shown by diastolic myocardial function	Effects of dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on diastolic myocardial function assessed via cardiac magnetic resonance imaging.	6 months, 12 months
Interaction between diabetes risk cluster and intervention on Myocardial function shown by diastolic myocardial function	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on diastolic myocardial function assessed via cardiac magnetic resonance imaging.	6 months, 12 months
Health economic evaluation shown by incremental cost-effectiveness ratio	Conducting a health economic evaluation from the perspective of the statutory health insurance and society in from of a cost-effectiveness analysis	6 months, 12 months
Interaction between diabetes risk cluster and intervention on health economic evaluation shown by incremental cost-effectiveness ratio	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on health economic evaluation shown by incremental cost-effectiveness ratio of a cost-effectiveness analysis	6 months, 12 months
Health economic evaluation shown by incremental cost-utility ratio	Conducting a health economic evaluation from the perspective of the statutory health insurance and society in from of a cost-utility analysis	6 months, 12 months
Interaction between diabetes risk cluster and intervention on health economic evaluation shown by incremental cost-utility ratio	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on health economic evaluation shown by incremental cost-utility ratio of a cost-utility analysis	6 months, 12 months
Changes in risk preferences	To test differences between the two treatment arms for the risk preferences	6 months, 12 months
Changes in time preferences	To test differences between the two treatment arms for the time preferences	6 months, 12 months
Interaction between diabetes risk cluster and intervention on prediabetes remission maintenance	To test interaction between diabetes risk clusters and intervention for 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.	12 months
Interaction between diabetes risk cluster and intervention on the risk preferences	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on change of risk preferences	6 months
Interaction between diabetes risk cluster and intervention on the risk preferences	To test interaction between diabetes risk clusters and intervention for effects of 6 months treatment with dapagliflozin 10 mg and lifestyle counseling compared to placebo and lifestyle intervention on change of time preferences	6 months

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Collaborators: AstraZeneca; German Federal Ministry of Education and Research; German Center for Diabetes Research

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2023
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: September 6, 2023
• First Submitted That Met QC Criteria: September 18, 2023
• First Posted (Actual): September 26, 2023

Study Record Updates

• Last Update Posted (Actual): July 24, 2025
• Last Update Submitted That Met QC Criteria: July 21, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperglycemia; Prediabetic State; Glucose Intolerance; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Dapagliflozin
• Other Study ID Numbers: LIFETIME

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No