The plasma levels of atrial natriuretic peptide and brain natriuretic peptide in type 2 diabetes treated with sodium-glucose cotransporter-2 inhibitor.

Abstract Purpose: The aim of this study was to determine the levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) after treatment with an SGLT2 inhibitor or DPP4 inhibitor in patients with type 2 diabetes mellitus that was inadequately controlled with insulin and to understand whether the variation of ANP may explain the favorable cardiovascular outcome. Methods: We enrolled 56 patients with type 2 diabetes mellitus that was inadequately controlled with insulin; the subjects were all 18∼80 years of age. After receiving a stable mean dose of ≥ 20 IU and ≤ 150 IU injectable insulin daily combined with or without no more than two oral antidiabetic agents for at least 8 weeks, patients who still experienced inadequate glycaemic control (HbA1c levels of 7.5∼10.5 %) were recruited. Findings: A total of 56 patients were enrolled in this study and randomized into three groups, including an SGLT2 inhibitor group (n=18), a DPP4 inhibitor group (n=19) and a placebo group (n=19). Patients who received SGLT2 inhibitor or DPP4 inhibitor treatment all had significantly decreased HbA1c levels, fasting blood glucose (FBG) levels and systolic blood pressure at 24 weeks compared with patients treated with a placebo. SGLT2 inhibitor treatment decreased ANP levels, BNP levels, systolic blood pressure and weight compared with placebo treatment. Compared with patients who received DPP4 inhibitor treatment, patients who received SGLT2 inhibitor treatment showed lower HbA1c levels (7.01 vs 7.58 % in the DPP4 inhibitor group; P =0.03), ANP levels (28.41 vs 43.03 pg/ml in the DPP4 inhibitor group; P =0.00), and weight (66.14 vs 71.76 kg in the DPP4 inhibitor group; P =0.04) at 24 weeks after adjusting for the baseline values. The SGLT2 inhibitor group showed higher sodium concentrations compared with the placebo group and the DPP4 inhibitor group (145.89 vs 143.89 and 144.79 mmol/l, respectively; P = 0.00 and P = 0.04) at 24 weeks. ANP and BNP levels were not significantly correlated with HbA1c and blood glucose levels. Implications: These results indicated that SGLT2 inhibitors may be superior to DPP4 inhibitor to help to significantly reduce the risk of development of the cardiovascular disease in patients with diabetes. But the major limitation concerns the little number of patients included within each group in this study. This small sample size could be enlarged in further research.