Abstract | BACKGROUND: METHODS: Sixty-six people with type 2 diabetes were randomized to 16 weeks of dapagliflozin 10 mg/day, exenatide 10 µg twice daily, dapagliflozin- exenatide, or placebo treatment. The effect of treatments on estimates of: (1) plasma volume (calculated by Strauss formula, bioimpedance spectroscopy, hematocrit, (2) autonomic nervous system activity (heart rate variability), (3) arterial stiffness (pulse wave applanometry), (4) systemic hemodynamic parameters including peripheral vascular resistance, cardiac output and stroke volume (all derived from non-invasively systemic hemodynamic monitoring), and (5) natriuresis (24-hour urine collection) were assessed after 10 days and 16 weeks of treatment. RESULTS: After 10 days, dapagliflozin reduced systolic BP (SBP) by - 4.7 mmHg, and reduced plasma volume. After 16 weeks, dapagliflozin reduced SBP by - 4.4 mmHg, and reduced sympathetic nervous system (SNS) activity. Exenatide had no effect on SBP, but reduced parasympathetic nervous system activity after 10 days and 16 weeks. After 10 days, dapagliflozin- exenatide reduced SBP by - 4.2 mmHg, and reduced plasma volume. After 16 weeks, dapagliflozin- exenatide reduced SBP by - 6.8 mmHg, and the reduction in plasma volume was still observed, but SNS activity was unaffected. CONCLUSIONS: The dapagliflozin-induced plasma volume contraction may contribute to the initial SBP reduction, while a reduction in SNS activity may contribute to the persistent SBP reduction. Dapagliflozin- exenatide resulted in the largest decrease in SBP. The effect on plasma volume was comparable to dapagliflozin monotherapy, and SNS activity was not reduced, therefore other mechanisms are likely to contribute to the blood pressure lowering effect of this combination, which need further investigation. Trial registration Clinicaltrials.gov, NCT03361098.
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Authors | Charlotte C van Ruiten, Mark M Smits, Megan D Kok, Erik H Serné, Daniël H van Raalte, Mark H H Kramer, Max Nieuwdorp, Richard G IJzerman |
Journal | Cardiovascular diabetology
(Cardiovasc Diabetol)
Vol. 21
Issue 1
Pg. 63
(04 28 2022)
ISSN: 1475-2840 [Electronic] England |
PMID | 35484607
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | © 2022. The Author(s). |
Chemical References |
- Benzhydryl Compounds
- Glucosides
- Hypoglycemic Agents
- Sodium-Glucose Transporter 2 Inhibitors
- dapagliflozin
- Exenatide
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Topics |
- Benzhydryl Compounds
- Blood Pressure
- Diabetes Mellitus, Type 2
(diagnosis, drug therapy)
- Exenatide
(adverse effects)
- Glucosides
- Humans
- Hypoglycemic Agents
(adverse effects)
- Sodium-Glucose Transporter 2 Inhibitors
(adverse effects)
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