Ps-c17-10: oral semaglutide reduces albuminuria in patients with type 2 diabetes, obesity and hypertension, with partial dependence on blood pressure control

Objective: GLP-1 receptor agonists reduce blood pressure (BP) and proteinuria in people living with type 2 diabetes (T2D) and obesity, but data on patients with uncontrolled hypertension are very scarce. Oral semaglutide showed interesting results in patients with moderate renal impairment in PIONEER 5, but their BP was well controlled, with SBP < 140 mmHg. We sought to assess the antiproteinuric effect of oral semaglutide in a group of patients with T2D, obesity and uncontrolled hypertension, and whether this effect is dependent on BP reduction. Design and Methods: Retrospective analysis of the data on SBP and albuminuria were performed in consecutive patients with T2D, obesity and uncontrolled hypertension (office sitting SBP < 140 mmHg) who started therapy with oral semaglutide. Data were obtained from a baseline visit in which oral semaglutide was initiated, and a second visit after 3–4 months. Mediation analyses with SBP reduction as mediator were performed post-hoc to quantify its relative contribution to albuminuria reduction. Patients who initiated or changed antihypertensive medication simultaneously with oral semaglutide were excluded. Consent was obtained from all included subjects. Results: Data were obtained from 33 patients, 21 (64%) were female, age 54.2 ± 11.9 years, diabetes duration 6.8 ± 2.7 years, baseline BMI 36.7 ± 5.2 kg/m2, baseline SBP 166 ± 12.2 mmHg, baseline eFGR (CKD-EPI) 58 ± 11.6 ml/min/1.73m 2 and baseline albuminuria (geometric mean) 134 ± 125 mg/g Cr, with 16 patients (48.5%) having < 30 mg/g, 12 (36.4%) 30–300 mg/g and 5 (15.1%) > 300 mg/g. SBP reduction was 4.8 ± 2.1 mmHg (p = 0.012, paired t-test), albuminuria reduction was 36 ± 27 mg/g (-27%; p = 0.026, paired t-test), and eGFR change + 1.3 ± 1.6 mL/min/1.73m 2 (not significant). There was a significant correlation between SBP and albuminuria reductions (Pearson's r: 0.26, p = 0.002). The mediation analyses showed that albuminuria reduction of 11 ± 10 mg/g (8.3%) was mediated by SBP reduction while 25 ± 14 mg/g (18.7%) was SBP-independent. 4 patients (12.1%) reduced their albuminuria to < 30 mg/g (Figure). Conclusions: In patients with T2D, obesity and uncontrolled hypertension, oral semaglutide significantly reduced SBP and albuminuria, without change in eGFR, and a relevant fraction of them (about 1/8) reduced albuminuria below the conventional normality threshold (< 30 mg/g). The decrease in albuminuria was only partially mediated by SBP reduction, suggesting additional mechanisms, possibly direct glomerular and/or tubular effects.