CONTINUOUS GLUCOSE MONITORING EVALUATIONOF REPLACING INSULIN GLARGINE U100 WITH INSULIN GLARGINE U300 AND HYPOGLYCEMIA IN TYPE 2 DIABETES MELLITUS (CERAH)

Abstract

INTRODUCTION
Despite being the most potent glucose-lowering agent, optimization of insulin therapy is often confounded by the risk of hypoglycemia. Insulin glargine U300 (Gla300) has equivalent glycemic efficacy but with benefit of a lower risk of hypoglycemia than glargine U100 (Gla-100). There has been no prior study on the risk of hypoglycemia comparing Gla-100 and Gla-300 using continuous glucose monitoring system (CGMS) among T2DM patients.

METHODOLOGY
This pilot project was a prospective, single-arm study. We recruited patients with T2DM who had previously experienced hypoglycemia while on Gla-100 and then were switched to Gla-300. We assessed the differences in hypoglycemic events measured by CGMS, the percentage of time below target range (<3.9 mmol/L and <3.0 mmol/L) and time within target range (3.9 – 7.8 mmol/L), before and 4 weeks after switching Gla-100 to Gla-300. The secondary outcomes were the changes in glycemic variability, HbA1c level, fructosamine level, dose of basal insulin and body weight from baseline to prior and 4 weeks after insulin switch.

RESULTS
Among the 60 patients who consented, 48 (80%) completed the study (mean age 63.4 years, disease duration 22.9 years). After switching to Gla-300, the number of CGMS detected clinically significant nocturnal hypoglycemia (<3.0 mmol/L) was reduced (0.275 vs 0.126 events per patient day, P=0.032). In those with nocturnal hypoglycemia, the percentage of nocturnal period below 3.9 mmol/L was significantly reduced with Gla-300 (15.96 vs 7.99%, P=0.027). Both HbA1c (8.269 vs 7.99%, P<0.001) and fructosamine (280.063 vs 248.125 umol/L, P<0.001) improved during Gla-100 phase. HbA1c level further reduced significantly (7.99 vs 7.77%, P=0.001) with no change in insulin dose and weight after 4 weeks of Gla-300. There was no change in glycemic variability.

CONCLUSION
Gla300 (switch from Gla-100) is effective within a short duration (4 weeks) in reducing the risk of clinically significant nocturnal hypoglycemic events and the percentage of time below range during nocturnal hours.