Abstract: FR-PO240
The Hemodynamic Effect of the GLP-1R Agonist Liraglutide in Diabetic Kidney Disease
Session Information
- Diabetic Kidney Disease: Advancing Treatment
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 602 Diabetic Kidney Disease: Clinical
Authors
- Wajdlich, Malgorzata Jadwiga, Medical Univercity in Lodz, Lodz, Poland
- Nowicki, Michal P., Medical Univercity in Lodz, Lodz, Poland
Background
The impact of GLP-1R agonists on blood pressure is a resultant of its vasodilatory and natriuretic effect and the increase of heart rate and sympathetic activity. The increased peripheral resistance resulting from the imbalance in factors regulating vascular tone and autonomic nervous system are important pathogenetic factors in the development of hypertension in diabetic kidney disease. The aim of the study was to investigate the hemodynamic effect of a single subcutaneous dose of 1.2 mg liraglutide compared to placebo in patients with type 2 diabetes mellitus and impaired renal function.
Methods
This cross-over study included 17 patients with eGFR below 30 ml/min/1.73 m2 and 17 patients with eGFR above 60 ml/min/1.73 m2. Blood pressure and heart rate were monitored noninvasively for 24 hours. Before and after each medication, systemic vascular resistance, heart rate variability, pulse wave velocity and central blood pressure were measured with signal morphology impedance cardiography and applanation tonometry.
Results
Significant increases of both 24h mean heart rate and cardiac output were noted in both groups. In patients with eGFR >60 ml/min/1.73 m2 mean 24h heart rate was 73±8 after liraglutide compared with 68±5 beats per minute after placebo (p=0.005), whereas in patients with eGFR <30 ml/min/1.73 m2 the respective values were 76±9 and 67±9 beats per minute (p<0.001 ). In the latter group it was additionally accompany by sympathetic predominance after GLP-1R agonist (p=0,005). The systemic vascular resistance was reduced after injection of liraglutide compared with placebo only in the study group with better preserved kidney function (p=0,002), whereas the pulse wave velocity was increased after GLP-1R analogue compared with placebo (p=0,0006), only in patients with eGFR <30 ml/min/1.73 m2. Additionally also only in this group after liraglutide 24h mean arterial pressure significantly increased from 97.8±8.1 to 102.4±8.6 mmHg compared to placebo (p=0.003).
Conclusion
Liraglutide administration in the patients with advanced chronic kidney disease may cause a transient increase of systemic blood pressure probably due to the increase of cardiac output. Increased cardiac output mainly depends on an acceleration of heart rate, which is probably associated with a sympathetic predominance. The vasodilatory effect can be preserved only in earlier stages of CKD.