Time Course of the RAAS.

BackgroundThe impact of sodium-glucose cotransporter-2 inhibitors (SGLT-2is), including dapagliflozin, on the renin-angiotensin-aldosterone system (RAAS) in type 2 diabetes mellitus (T2DM) patients remains controversial, as they may either activate or inhibit RAAS, subsequently influencing glucose metabolism and the accuracy of the aldosterone-to-renin ratio (ARR) in diagnosing primary aldosteronism (PA). However, the effects of SGLT-2is therapy on RAAS and their correlation with glucose metabolism have not been well studied.MethodsA cohort of 147 patients with T2DM and hypertension was prospectively recruited and categorized into two groups: diabetic kidney disease group (DKD, n = 73) and non-DKD group (n = 74), based on diagnostic criteria for diabetic complications. Patients were prescribed 10 mg dapagliflozin daily for 3 months. The primary outcome measure was the change in renin (REN) levels during outpatient visits at baseline, 1 month, and 3 months. The secondary outcome was the change in other metabolic biomarkers from baseline to the 3-month visit. To evaluate the relationship between RAAS components and various glucose metabolism indicators, including HbA1c, FBG, CP, HOMA-β, HOMA-IR, and UACR, Spearman correlation and multiple linear regression analyses were conducted at baseline and 3-month visit.ResultsAfter 3 months, the BMI, HbA1c, FBG, TG, TCHO, SBP, DBP, UACR, and HOMA-IR levels were significantly decreased, while Crea and HOMA-β were significantly increased from the baseline in both groups. Additionally, the differences from the baseline in FBG (−2.64 ± 2.66 vs. −1.70 ± 1.92 mmol/L) and UACR (−355.01 ± 1534.12 vs. −4.66 ± 7.86 mg/g) values were significantly higher in DKD group than those in non-DKD group. REN levels increased significantly from baseline at 1-month visit (4.15 ± 7.35 vs. 2.75 ± 8.03 ng/L; DKD vs. non-DKD; between-group difference, p p > 0.05) and 3-month visit (−0.45 ± 1.15 vs. −0.42 ± 1.07; between‑group difference, p > 0.05) in both groups (within‑group change vs. baseline, p p p ConclusionsThe correlations between RAAS markers and glucose metabolism indices were significantly attenuated, potentially due to lowered blood glucose levels after SGLT‑2is treatment. However, it is noteworthy that short-term therapy may elevate REN levels and reduce ARR, potentially resulting in false-negative outcomes in PA screening.