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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
170
Dapagliflozin 10 mg once daily for 6 months. Route of administration: oral.
Placebo matching Dapaglifolzin once daily for 6 months. Route of administration: oral.
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).
Charité Universitätsmedizin Berlin, Klinik für Endokrinologie und Stoffwechselmedizin
Berlin, Germany
RECRUITINGUniversitätsstudienzentrum für Stoffwechselerkrankungen , Medizinische Klinik und Poliklinik III
Dresden, Germany
RECRUITINGGerman Diabetes Center, Leibniz-Center for Diabetes Research at the Heinrich-Heine-University Duesseldorf
Düsseldorf, Germany
RECRUITINGHeidelberg University Hospital - Department of Endocrinology and Metabolism
Heidelberg, Germany
RECRUITINGMedizinische Klinik und Poliklinik III - Bereich Endokrinologie
Leipzig, Germany
RECRUITINGMedizinische Klinik I, UKSH Campus LübeckAG Meyhöfer - Endocrinology, Diabetes & Metabolism
Lübeck, Germany
RECRUITINGDiabetes Center Med. Klinik und Poliklinik IV, Klinikum der Universität München, LMU
München, Germany
RECRUITINGInstitut für Ernährungsmedizin, Technische Universität München
München, Germany
RECRUITINGUniversity Hospital Tuebingen, Otfried-Mueller Str. 10
Tübingen, Germany
RECRUITINGFrequency 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.
Time frame: 6 months
Reduction of urinary albumine-creatinine ratio.
To test differences between the two treatment arms for reduction of urinary albumine-creatinine ratio.
Time frame: 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).
Time frame: 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).
Time frame: 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
Time frame: 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
Time frame: 12 months
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