Patient-reported outcomes in transition from high-dose U-100 insulin to human regular U-500 insulin in severely insulin-resistant patients with type 2 diabetes: analysis of a randomized clinical trial

Abstract

Background: Initiation and titration of human regular U-500 insulin (U-500R) with a dosing algorithm of either thrice daily (TID) or twice daily (BID) improved glycemic control with fewer injections in patients with type 2 diabetes treated with high-dose, high-volume U-100 insulin. The objective of this analysis was to compare patient-reported outcomes between U-500R TID and BID treatment groups in this titration-to-target randomized, clinical trial.

Methods: In this 24-week, open-label, parallel trial, 325 patients were randomized to TID (n = 162) or BID (n = 163) U-500R after a 4-week lead-in period (screening). The Treatment Related Impact Measure-Diabetes (TRIM-D) and EQ-5D-5L questionnaires were administered at screening, baseline/randomization, and endpoint (24 weeks). The Visual Analog Scale-Injection Site Pain (VAS-ISP) was assessed at baseline/randomization, 12 weeks, and endpoint.

Results: The TRIM-D showed statistically significant improvements in overall scores from baseline to endpoint for both BID and TID groups, most domains in the TID group, and all domains in the BID group. The BID group achieved better scores than the TID patients in overall and in treatment burden, daily life, and compliance domains (p < .05). EQ-5D-5L index scores showed no statistically significant differences for TID and BID groups (and no differences between TID and BID groups) from baseline to endpoint. VAS-ISP scores improved for both treatment groups (-5.60 TID; -6.47 BID; p < .05 for both) from baseline to endpoint.

Conclusions: U500 can be successfully titrated for improved glycemic control using BID and TID regimens with diabetes-specific Patient-Reported Outcomes showing improvements in both arms; however, BID had better scores than TID in overall, treatment burden, daily life, and compliance domains.

Trial registration: These secondary analyses are based on the study first received January 22, 2013 and reported in Clinical Trial Registry No.: NCT01774968 .

Keywords: High-dose insulin therapy; Patient compliance; Patient-reported outcomes; Severe insulin resistance; Type 2 diabetes mellitus; U-500R.

Figures

Fig. 1

Visual Analog Scale - Injection Site Pain evaluation from baseline to endpoint. Abbreviations: BID = twice daily; SD = standard deviation; TID = thrice daily; VAS = visual analog scale. *Actual mean values of patients on U100 insulins ± SD are from corrected CRF data. **p-values are <0.05 for visit 12 and visit 16 when least square mean change from baseline are calculated (−7.36 TID, -5.85 BID visit 12 and -5.60 TID, -6.47 BID visit 16)