SGLT2 inhibition increases serum copeptin in young adults with type 1 diabetes

Abstract

Aims: Copeptin, a surrogate of vasopressin, is elevated in type 1 diabetes (T1D) and predicts kidney disease and cardiovascular mortality. Given the cardiorenal protective effects of SGLT2 inhibition (SGLT2i), our aim was to examine: 1) the relationship between serum copeptin, metabolic, renal and systemic hemodynamic parameters in adults with T1D; and 2) serum copeptin after SGLT2i with empagliflozin.

Materials and methods: In this post-hoc, exploratory analysis, serum copeptin, glomerular filtration rate (GFR_Inulin), effective renal plasma flow (ERPF_PAH), plasma renin angiotensin aldosterone system markers, HbA_1c, 24-hour urine volume and sodium excretion were measured in 40 participants with T1D (24.3±5.1 years) during eu- and hyperglycaemia before and after 8 weeks of 25mg of daily empagliflozin.

Results: Higher baseline copeptin correlated with higher HbA_1c, lower 24-hour urine volume and sodium excretion, after correcting for age, sex, systolic blood pressure, and HbA_1c. Copeptin concentrations increased in response to empagliflozin under euglycaemia (4.1±2.1 to 5.1±2.8pmol/L, P=0.0053) and hyperglycaemia (3.3±1.4 to 5.6±2.8pmol/L, P<0.0001). The rise in copeptin in response to empagliflozin correlated with change in 24-hour urine volume, but was independent of changes in fractional excretion of sodium and haematocrit.

Conclusions: Elevated serum copeptin was associated with worse glycaemic control and lower diuresis and natriuresis. SGLT2i increased serum copeptin in adults with T1D, and the rise correlated with change in diuresis, but not natriuresis and hemo-concentration. Further work is required to evaluate the clinical implications of elevated copeptin with SGLT2i, including whether it is simply a marker of diuresis or may contribute to cardiorenal disease long-term.

Keywords: Copeptin; SGLT2 inhibition; Type 1 diabetes.