SGLT2 inhibitors, hydrochlorothiazide lowered sympathetic nerve activity
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Key takeaways:
- SGLT2 inhibitors and hydrochlorothiazide both reduced muscle sympathetic nerve activity.
- Empagliflozin also improved glycemic control.
SGLT2 inhibitors and hydrochlorothiazide both reduced muscle sympathetic nerve activity in patients with diabetes, but recent data show one of the therapies could lead to more weight loss and better glycemic control.
“Reductions in sympathetic nervous system activity may contribute to beneficial effects of sodium glucose transporter 2 (SGLT2) inhibition on cardiovascular outcomes,” Karsten Heusser, of the Institute of Aerospace Medicine at the German Aerospace Center in Cologne, Germany, and colleagues wrote. “We tested the hypothesis that SGLT2 inhibition with empagliflozin lowers muscle sympathetic nerve activity in type 2 diabetes compared with hydrochlorothiazide.”
The parallel, double-blind trial included 38 randomly selected patients with type 2 diabetes on metformin monotherapy to either 25 mg/day empagliflozin or 25 mg/day hydrochlorothiazide for 6 weeks. Groups were split for matched analysis, with 18 patients in the empagliflozin group and 20 in the hydrochlorothiazide group. Participants, followed from December 2017 to April 2020, had to have hemoglobin A1c values between 6.5% and 10%, BMI between 25 kg/m2 and 40 kg/m2, systolic blood pressure between 110 mm Hg and 160 mm Hg and diastolic blood pressure above 60 mm Hg at the start.
Researchers assessed nerve activity using peroneal microneurography, while blood pressure, cardiovascular and metabolic biomarkers were measured at baseline and at the end of the trial.
Results signaled that both drugs caused volume depletion, shown by increased thoracic impedance. Empagliflozin, however, triggered a 1.23 kg greater body weight loss than hydrochlorothiazide (P = .011). The drug also improved glycemic control, per the findings. Both treatments decreased seated systolic blood pressure (P < .002).
Muscle sympathetic nerve activity did not change significantly with empagliflozin or with hydrochlorothiazide, according to the researchers, although the drugs were negatively correlated with body weight changes.
“Increased renal sodium excretion eliciting body weight loss may promote sympathetic activation,” the authors wrote. “However, sympathetic excitation in the face of increased sodium loss may be attenuated by SGLT2 inhibitor-specific actions.”
Overall, the research “provides insight in pharmacological actions of SGLT2 inhibitors on human cardiovascular autonomic control, which may have relevance for cardiovascular outcomes,” they continued. “Given the important role of the sympathetic nervous system in the progression of cardiovascular disease, mechanisms attenuating sympathetic activity in the face of increased sodium excretion deserve further attention.”
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