Continuous Subcutaneous Insulin Infusion May Reduce Basal Hyperglycemia in T2D

Patients with type 2 diabetes (T2D) who have not responded to multiple dose injection (MDI) of insulin may benefit from treatments that target basal hyperglycemia (BHG) levels, according to a post-hoc analysis of data from the OPT2MISE trial (NCT identifier: NCT01182493), published in Diabetes, Obesity, and Metabolism. BHG made a significant contribution to total hyperglycemia levels.      

OPT2MISE was a multicenter, parallel-group, randomized, controlled clinical trial.  Patients with T2D achieving suboptimal glucose control on a basal-bolus insulin regimen were enrolled in the study. The efficacy and safety of continuous subcutaneous insulin infusion (CSII) was compared with MDI of insulin after an 8-week period of insulin dose optimization (≥0.7 and ≤1.8 U/kg/d). The primary end point of the study was the between-group difference in mean glycated hemoglobin A1c (HbA1c) change from baseline to the end of therapy. 

The post-hoc analysis involved comparisons of hyperglycemic area under the curve (AUC) from the 24-h basal period (AUC-B) and post-prandial period (AUC-P). The contribution of these parameters to total hyperglycemia was investigated. Patients were divided into 5 subgroups based on HbA1c levels (Group 1: <8%, Group 2: 8% to 8.4%, Group 3: 8.5% to 8.9%, Group 4: 9% to 9.4%, and Group 5: ≥9.5%).  

Patients using MDI showed AUC-B decreases of 21.6% to 54.8% in groups 1 to 4 (P=.0138 and P=.0002, respectively) vs group 5.  No significant differences in AUC-P were noted across groups (P=.1009). 

Patients on CSII showed AUC-B and AUC-P decreases of 21% to 17% for groups 1 to 4 (P=.0007 and P=.05, respectively), vs group 5.  Non-responders vs responders to CSII therapy showed no difference in AUC-B or AUC-P. 

“In the present work, we demonstrate that the BHG contribution predominates across a large range of HbA1c from <8% to >9.5% and represents ~80% of hyperglycemia exposure in patients with the highest HbA1c. In contrast, [postprandial hyperglycemia] accounts for only 20-30% of overall hyperglycemia regardless of the baseline HbA1c level. These data clearly show that failure of intensified [MDI] therapy results mainly from the inability of high-dose long-acting insulin to control BHG. Therefore, the main therapeutic goal would be to target BHG.”

Disclosures: Funding was provided by Medtronic International Trading Sarl, Tolochenaz, Switzerland.  The authors declare affiliations with the pharmaceutical industry, please refer to the full text.

Reference

Reznik Y, Habteab A, Castaneda J, Shin J, Joubert M.  Contribution of basal and postprandial hyperglycemia in type 2 diabetes patients treated by an intensified insulin regimen: impact of pump therapy in the OPT2MISE trial [published online June 4, 2018].  Diabetes Obes Metab.  doi:10.1111/dom.13398