DiEtary Sodium Intake Effects on Ertugliflozin-induced Changes in GFR, reNal Oxygenation and Systemic Hemodynamics: the DESIGN Study, a Randomized, Placebo-controlled, Cross-over Study With Ertugliflozin in People With Type 2 Diabetes
SGLT2 inhibitors have demonstrated to mitigate cardiorenal risk in people with type 2 diabetes and are likely to play an increasingly large role in the treatment of patients with diabetes, chronic kidney disease and hypertension. Yet the underlying mechanisms of its protective effects are incompletely understood and the salutary effect may be altered by dietary factors such as sodium intake. Therefore, carefully designed mechanistic trials are needed to better understand the interplay between ertugliflozin and salt intake and to potentially modify salt intake to maximize treatment response. In addition, the study could contribute to hypotheses concerning the effects of SGLT2 inhibitors in combination with other drugs that affect sodium homeostasis and could help to explain the differences in kidney outcomes observed in (outcome) trials, which include different ethnicities with potential differences in dietary habits.
⁃ Adults with previously diagnosed T2DM according to American Diabetes Association (ADA) criteria
• HbA1c 6.5-10%
• Age 18 - 85 years of age
• Overweight or obese with BMI: \>25 kg/m2
• We will make every effort to enrol participants of all races/ethnicities.
• Both sexes (females must be post-menopausal; no menses \>1 year; in case of doubt, Follicle-Stimulating Hormone (FSH) will be determined with cut-off defined as \>31 U/L)
• Ability to provide signed and dated, written informed consent prior to any study procedures
• Estimated GFR 60-90 ml/min/1.73m2 by CKD-EPI matching the eGFR range of most participants in VERTIS-CV
• Sodium intake at baseline \< 200 mmol/day
• UACR \< 30 mg/mmol
• All participants need to be on a stable dose of diabetes medication, including Metformin, SU, DPP4-inhibitors, or insulin.
• Participants suffering from hypertension need to be on a stable dose of RAS inhibitors. In case RAS inhibition is not tolerated, the participant should to be on a stable dose of other antihypertensive treatment.