Predicting the response to SGLT-2 inhibitors as add-on therapy to multiple day injection insulin with glycated albumin: a pilot study.

Abstract

Achieving optimal glycemic targets is the main therapeutic goal in patients with type 2 diabetes (T2D) mellitus. HbA1c is the reference biomarker for monitoring glycemic control; however, in specific conditions affecting erythrocyte turnover or in patients on multiple daily injection (MDI) insulin regimens, the determination of glycated albumin (GA) may be preferable. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors represent a novel class of antidiabetic drugs that lower plasma glucose concentrations quickly, with insulin-independent mechanisms. Herein, we explored the role of GA in predicting the short-term response to SGLT-2 inhibitors as add-on to MDI insulin. Sixteen patients with long-standing, poorly controlled T2D on MDI insulin starting an SGLT-2 inhibitor were subjected to plasma GA and HbA1c measurements at 30 days intervals for up to 3 months in order to examine the temporal changes of these glycemic biomarkers. At the end of the study, grossly coincident with the life span of erythrocytes, a significant decrease in median HbA1c was observed, (from 8.7 [range: 8.2-9.3%] at baseline to 7.2 [range: 7.0-7.9%]), with the advantage of less insulin dose requirements. However, significant, and incremental reductions in median GA determinations could be already evident after 30 days (-3.5 [range: -7.5, -2.5%]) and 60 days (-6.4 [range: -10.5, -4.7%]) from the start of SGLT-2 inhibitor treatment and persisted for up to 3 months (-8.6 [range: -12.1, 6.1%]). The decrements of HbA1c observed at the 3-month visit were highly correlated with the concurrent absolute reductions of plasma GA (ρ=0.550, P=0.027), whereas a borderline significance could be demonstrated with reference to reductions in plasma GA at 30 and 60 days. Although limited by the small number of participants, these preliminary findings suggest that GA, rather than HbA1c, could represent a useful and reliable biomarker in T2D to monitor the early glucose-lowering effects of antidiabetic drugs with rapid onset of action, such as SGLT-2 inhibitors and MDI insulin.