Kidney Week

Abstract: SA-PO139

Effect of Dapagliflozin on Cardiac Function and Biomarkers in Patients with Type 2 Diabetes and Albuminuria – A Randomized Study

Session Information

• Diabetic Kidney Disease: Clinical - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Eickhoff, Mie K., Steno Diabetes Center Copenhagen, Gentofte, Denmark

Mie K. Eickhoff,

• Olsen, Flemming Javier, Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen, Denmark

Flemming Javier Olsen,

• Frimodt-Moller, Marie, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Marie Frimodt-Moller,

• Díaz, Lars J., Steno Diabetes Center Copenhagen, Gentofte, Denmark

Lars J. Díaz,

• Faber, Jens, Herlev University Hospital , Herlev, Denmark

Jens Faber,

• Jensen, Magnus Thorsten, Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen, Denmark

Magnus Thorsten Jensen,

• Rossing, Peter, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Peter Rossing,

• Persson, Frederik, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Frederik Persson,

Background

Sodium glucose cotransporter 2 inhibitors (SGLT2i) have shown cardio- and reno-protective properties. The aim here is to evaluate the effect of dapagliflozin (dapa) treatment on myocardial function assessed with advanced echocardiography (TTE), and cardiac biomarkers when added to standard care in patients with type 2 diabetes (T2D).

Methods

This is a sub-study of a double-masked randomized placebo-controlled crossover trial of 12 weeks treatment with dapa 10 mg once daily or placebo. All patients (n=40) were on RAS blocking treatment, had T2D and albuminuria at baseline. At the end of the treatment period TTE was performed, ⁵¹Cr-EDTA, albuminuria and 24h blood pressure were measured, as well as cardiac markers in plasma; NTproBNP, troponin I, MRproANP, MRproADM, TNF-α, IL-6 and copeptin.
Global longitudinal strain (GLS) was the primary systolic echocardiographic endpoint. To assess diastolic function a combined diastolic endpoint was used including mean early diastolic myocardial velocity (e’), ratio between early transmitral inflow velocity (E) and e’ (E/e’), atrial volume and pulmonary pressure (TRmaxPG).

Results

Baseline geometric mean urinary albumin creatinine ratio (UACR) was 147 (IQR 75-289) mg/g, mean eGFR 85 (SD±19.7) ml/min/1.72 m². Baseline HbA_1c was 73 (SD±15) mmol/mol, 24h blood pressure 148/82 (SD±12.5/7.7) mmHg, diabetes duration 16.5 (SD±4,8) years, age 65 (SD±8) years and 90% were male.
After 12 weeks treatment with dapa vs. placebo, HbA_1c was reduced by 7.4 (5-10) mmol/mol (p<0.01) and 24h blood pressure decreased 4.8/2.7 mmHg (p=0.023/0.031). Left ventricular ejection fraction after placebo was 55.5 (SD±6.7) % and 53.7 (SD±6.7) % after active treatment – a non-significant change. GLS did not change whereas diastolic function improved significantly with 19.8% (3.3-36.3%, p = 0.021). Plasma concentration of NTproBNP, troponin I, MRproANP, MRproADM, TNF-α and IL-6 did not change. Plasma concentration of copeptin increased with 32.3% (p<0.0001).

Conclusion

Treatment of dapa 10 mg vs. placebo in patients with albuminuria was associated with an improvement in diastolic function but not in GLS in people with T2D and albuminuria. Also an increase in copeptin was observed possibly reflecting increased diuresis due to natriuresis.

Funding

• Commercial Support –