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

BACKGROUND: 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 albu-min (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.METHODS: 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.RESULTS: 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 evi-dent 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 (rho=0.550, P=0.027), whereas a border-line significance could be demonstrated with reference to reductions in plasma GA at 30 and 60 days.CONCLUSIONS: 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.

Automated summary

In patients with poorly controlled T2D on MDI insulin starting an SGLT-2 inhibitor, reductions in plasma GA concentrations may be more predictive of short-term response than HbA1c levels, indicating the potential utility of GA as a biomarker for monitoring early glucose-lowering effects of rapid-acting antidiabetic drugs like SGLT-2 inhibitors and MDI insulin.