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

NCT06054035 | Recruiting Phase 4

• 1 other identifier: LIFETIME
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 9

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Reduction of urinary albumine-creatinine ratio.

  1 month throuhg 6 months

• Change in estimated glomerular filtration rate (eGFR)

  7 months

• 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)

  3 months through 12 months

• Prediabetes remission maintenance

  12 months

Other Outcomes (52)

• Insulin sensitivity

  6 months, 12 months

• Insulin secretion

  6 months, 12 months

• Number of patients progressing to Type 2 Diabetes

  6 months, 12 months

Study Arms (2)

Dapagliflozin (Forxiga®) and lifestyle counselling

EXPERIMENTAL

Drug: Dapagliflozin (Forxiga®); Behavioral: Lifestyle Intervention

Placebo matching Dapaglifolzin and lifestyle counselling

PLACEBO COMPARATOR

Drug: Placebo matching Dapaglifolzin; Behavioral: Lifestyle Intervention

Interventions

Dapagliflozin (Forxiga®) DRUG

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

Dapagliflozin (Forxiga®) and lifestyle counselling

Placebo matching Dapaglifolzin DRUG

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

Placebo matching Dapaglifolzin and lifestyle counselling

Lifestyle Intervention 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).

Dapagliflozin (Forxiga®) and lifestyle counselling; Placebo matching Dapaglifolzin and lifestyle counselling

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• German Federal Ministry of Education and Research: collaborator
• German Center for Diabetes Research: collaborator
• AstraZeneca: collaborator

Study Sites (9)

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, 40225, Germany

RECRUITING

Heidelberg University Hospital - Department of Endocrinology and Metabolism

Heidelberg, 69120, Germany

RECRUITING

Medizinische Klinik und Poliklinik III - Bereich Endokrinologie

Leipzig, Germany

RECRUITING

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

Lübeck, 23562, 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, 72076, Germany

RECRUITING

MeSH Terms

Conditions

Prediabetic State; Renal Insufficiency

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Central Study Contacts

Andreas Birkenfeld, Prof. Dr.

CONTACT

0049707129; andreas.birkenfeld@med.uni-tuebingen.de

Andreas Fritsche, Prof. Dr.

CONTACT

0049707129; andreas.fritsche@med.uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomization will be performed stratified by prediabetes cluster.

Study Record Dates

• First Submitted: September 6, 2023
• First Posted: September 26, 2023
• Study Start: October 26, 2023
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: July 24, 2025

Record last verified: 2025-07

Locations

DE (9)