Treatment with dapagliflozin was not found to be associated with significant changes in blood pressure variability in patients with type 2 diabetes, according to research published in the American Journal of Hypertension.

Although the relationship between blood pressure variability, cardiovascular events, and renal events is relatively clear, there have been no studies that evaluated the effects of sodium-glucose co-transporter 2 (SGLT-2) inhibitors on blood pressure variability. Investigators therefore conducted research to investigate the effects of dapagliflozin on short-term blood pressure variability indices through 24-hour ambulatory blood pressure monitoring in people with type 2 diabetes. 

The current study is a secondary analysis of a double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT02887677) that investigated the effect of dapagliflozin on changes in 24-hour aortic systolic blood pressure in individuals with type 2 diabetes. Participants were evaluated and began 24-hour ambulatory blood pressure monitoring; the following day, participants were randomly assigned 1:1 to receive either oral dapagliflozin 10 mg/d or matching placebo for a 12-week period.


Continue Reading

The study cohort included 43 participants with type 2 diabetes and 42 participants in the placebo group. Both groups were similar in terms of age, body mass index, and the presence of comorbidities including hypertension, dyslipidemia, and coronary artery disease, as well as smoking status and treatment with antihypertensive agents, hypoglycemic agents, and statins.

The investigators reported that overall 24-hour systolic and diastolic blood pressure values were reduced in the treatment group compared with the placebo group (-5.80±9.48 vs -0.10±8.70 mm Hg and -2.23±5.26 vs 0.10±5.70, respectively). Reductions were also noted in 24-hour aortic systolic and diastolic blood pressure values (-4.12±8.00 vs -0.65±7.77 and -1.63±5.23 vs 0.16±5.99, respectively).

Systolic blood pressure indices were not significantly different between baseline and the final visit in either group. In the dapagliflozin group, brachial systolic blood pressure indices were numerically lower at the conclusion of the study, but these changes were not clinically or statistically significant. Similarly, brachial diastolic blood pressure indices did not change with dapagliflozin treatment.

In the placebo group, no differences in any indices were noted, nor were there any significant differences for any of the 24-hour blood pressure variability indices.

The investigators also evaluated brachial systolic and diastolic blood pressure during daytime and nighttime periods of the 24-hour recordings. During the day, no significant difference between baseline and the study conclusion in any index of blood pressure variability was noted in either group. During the night, nonsignificant slight reductions in almost all indices were noted in the dapagliflozin group from baseline through the study’s end. In the control group, all indices were noted to be “slightly but insignificantly increased” by week 12.

In the dapagliflozin group, the researchers also noted that the percentage of reverse dippers was slightly reduced, although the distribution of the dipping profiles was no different from baseline to conclusion for dippers, nondippers, and reverse dippers (25.6%, 48.8%, and 25.6% compared with 25.6%, 60.5%, and 14%, respectively).

The primary study limitation is that it was powered using the between-group difference in change in 24-hour aortic systolic blood pressure from baseline to study conclusion as the primary endpoint; therefore, results of this analysis should be considered hypothesis generating.

“The findings of the present study indicated that treatment with dapagliflozin was not associated with significant effects on [blood pressure variability] in patients with [type 2 diabetes],” the researchers wrote. “These results suggest that changes in short-term [blood pressure variability] in diabetic patients do not accompany all modes of [blood pressure] reduction, but only those where a modification of responsible pathogenic mechanisms are involved.”

“Further studies are warranted to elucidate these complex phenomena and associations, as well as assess whether SGLT-2 inhibitors would affect other types of [blood pressure variability] in patients with [type 2 diabetes],” they concluded.

Disclosure: This clinical trial was supported by AstraZeneca SA, Greece. Please see the original reference for a full list of authors’ disclosures.

Reference

Papadopoulou E, Theodorakopoulou MP, Loutradis C, et al. Dapagliflozin does not affect short-term blood pressure variability in patients with type 2 diabetes mellitus. Am J Hypertens. 2021;34(4):404-413. doi:10.1093/ajh/hpaa207