Elsevier

Endocrine Practice

Volume 16, Issue 5, September–October 2010, Pages 778-784
Endocrine Practice

Original Article
A Prospective Trial of U500 Insulin Delivered by Omnipod in Patients With Type 2 Diabetes Mellitus and Severe Insulin Resistance

https://doi.org/10.4158/EP10014.ORGet rights and content

ABSTRACT

Objective

To test the effectiveness and safety of U500 regular insulin delivered by continuous subcutaneous insulin infusion (CSII) via the Omnipod insulin delivery system in patients with uncontrolled type 2 diabetes mellitus and severe insulin resistance.

Methods

In this prospective, 1-year, proof-of-concept trial, patients with insulin-requiring type 2 diabetes who had a hemoglobin A1c level of 7.0% or higher and severe insulin resistance (average insulin requirement, 1.74 units of insulin per kilogram each day; range, 1.4 to 2.64 units of insulin per kilogram [average insulin dose, 196.4 units daily]) were identified at routine office visits at Mountain Diabetes and Endocrine Center in Asheville, North Carolina, between December 2007 and August 2008. All patients had been on intensive insulin therapy with or without oral agents for more than 3 months. All patients were switched from baseline failed therapy to U500 regular insulin by continuous subcutaneous insulin infusion via Omnipod. Effectiveness was assessed by hemoglobin A1c measurement and 72-hour continuous glucose monitoring at baseline and at weeks 13, 26, and, 52 and by treatment satisfaction assessed by the Insulin Delivery Rating System Questionnaire at baseline and at week 52 while on U500 via Omnipod.

Results

Twenty-one adults were enrolled (mean age, 54 years; mean duration of diabetes, 4 years; mean body mass index, 39.4 kg/m2; mean insulin requirement, 1.7 U/ kg per day; and mean hemoglobin A1c, 8.6%) whose previous treatment with U100 insulin regimens had failed. Twenty patients completed the study. Treatment with U500 insulin via Omnipod significantly reduced hemoglobin A1c by 1.23% (P < .001) and significantly increased the percentage of time spent in the blood glucose target range (70- 180 mg/dL) by 70.75% as assessed by continuous glucose monitoring (P < .001) without a significant increase in hypoglycemia. Patients were satisfied with treatment with U500 insulin via Omnipod, and 14 patients elected to remain on treatment at study completion.

Conclusions

U500 insulin delivered subcutaneously continuously via Omnipod is a safe and effective method of insulin delivery in the very insulin-resistant type 2 diabetic population. (Endocr Pract. 2010;16:778-784)

Section snippets

INTRODUCTION

The global epidemics of obesity and type 2 diabetes mellitus are driving the need to deliver ever-increasing insulin doses to a growing population of patients with type 2 diabetes and severe insulin resistance (absolute insulin requirement of more than 200 units of insulin per day, or more than the usual insulin requirement of approximately 1 to 1.2 units of insulin per kilogram of body weight per day in patients with type 2 diabetes). Delivering high doses of U100 insulin or insulin analogues

RESARCH DESIGN AND METHODS

In this prospective, 1-year, proof-of-concept trial, patients with insulin-requiring type 2 diabetes who had a hemoglobin A1c (HbA1c) level of 7.0% or higher and severe insulin resistance (average insulin requirement, 1.74 units of insulin per kilogram each day; range, 1.4 to 2.64 units of insulin per kilogram [average insulin dose, 196.4 units daily]) were identified at routine office visits at Mountain Diabetes and Endocrine Center in Asheville, North Carolina, between December 2007 and

RESULTS

Twenty-one patients (14 men and 7 women) ranging in age from 32 to 72 years were enrolled in the study. The baseline characteristics of the study cohort are summarized in Table 1. Twelve patients used oral insulin sensitizers (metformin [n = 10]), a thiazolidinedione (n = 1), or both metformin and a thiazolidinedione (n = 1) along with highdose insulin therapy. Eighteen patients initially used MDI; the remaining 3 patients initially used CSII. Twenty of 21 patients completed the 12-month study.

DISCUSSION

This prospective pilot study was designed to test the effectiveness and safety of U500 insulin in CSII delivered via the Omnipod insulin delivery system to a group of patients with uncontrolled type 2 diabetes and severe insulin resistance with extremely high insulin requirements. These high insulin requirements had resulted in chronic poor glycemic control due to a combination of poor absorption of high volumes of injected U100 insulin and poor adherence to an uncomfortable and ineffective

CONCLUSION

Our findings indicate that patients with uncontrolled type 2 diabetes and severe insulin resistance with insulin requirements exceeding 1.4 U/kg per day on U100-based intensive insulin regimens may improve glycemic control by switching therapy to CSII using U500 regular insulin. Therapy with U500 insulin by CSII was associated with weight gain in most, but not all, patients. The Omnipod was a highly acceptable method of insulin delivery for use with U500 insulin in this cohort. Presently, U500

DISCLOSURE

Dr. Wendy S. Lane and Dr. Stephen L. Weinrib are on the speaker’s bureau for Eli Lilly. Dr. Jonathan M. Rappaport and Ms. Therese Przestrzelski have no multiplicity of interest to disclose.

ACKNOWLEDGMENT

This research was made possible through grants from Insulet Corporation and Eli Lilly, Inc. The authors wish to thank Chris Hale, MA, CRC, for excellent technical assistance with this manuscript and for performing the statistical analyses and Jay Skyler, MD, for his support and encouragement.

REFERENCES (17)

There are more references available in the full text version of this article.

Cited by (37)

  • The switch from rapid-acting to concentrated regular insulin improves glucose control in type 2 diabetes patients on pump therapy: A cohort survey

    2022, Diabetes and Metabolism
    Citation Excerpt :

    The use of a more concentrated insulin may be offered to patients with T2DM in the context of high insulin requirements and/or suboptimal glucose control. Small retrospective series have shown an improvement of glucose control with the use of 500 U/ml (U-500) regular insulin administered by MDI [3–7] or by CSII using a pump device [8–11]. Only one retrospective uncontrolled study has examined the long-term efficacy of concentrated insulin use in pumps for treating T2DM [12].

  • Microdosing for drug delivery application—A review

    2021, Sensors and Actuators, A: Physical
    Citation Excerpt :

    The finding that OmniPod increases patients well-being compared to multiple daily injections (MDI) or durable pump therapy was confirmed by other studies [189,193,194]. Further studies are conducted towards diabetes type II therapy using U-500 insulin, also showing promising results [195]. Research on future therapies, such as an artificial pancreas implant, also use the OmniPod as dosing unit [196,197].

  • New developments in insulin therapy for type 2 diabetes

    2014, American Journal of Medicine
    Citation Excerpt :

    In a subsequent 1-year, proof-of-concept trial in 21 patients with type 2 diabetes requiring insulin treatment, HbA1c level ≥7.0%, and severe insulin resistance, it was demonstrated that treatment with insulin U500 via the OmniPod system significantly reduced HbA1c by 1.23% (P < .001) and significantly increased the percentage of time spent in the blood glucose target range (70–180 mg/dL) by 70.75% as assessed by continuous glucose monitoring (P < .001) without a significant increase in hypoglycemia. At the end of the study period, 14 of 20 patients who completed the study elected to remain on treatment.93 The V-Go system is aimed at a type 2 diabetes population requiring basal and bolus insulin.

  • Severe Insulin Resistance Due To C.576CG (P.I119M) Mutation In The Insr Gene: Case Report

    2017, AACE Clinical Case Reports
    Citation Excerpt :

    It has been shown that U-500 regular insulin can control hyperglycemia in obese patients with severe insulin resistance requiring >200 units/day (11). Continuous subcutaneous U-500 insulin delivery is also effective in type 2 diabetes with severe insulin resistance or lipodystrophy (12–14). Recombinant human IGF-I (rhIGF-I), on the other hand, is effective in the treatment of insulin resistance related to receptorpathy (15).

View all citing articles on Scopus
View full text