Use Of U-500 Insulin Research Articles

956-P: Successful Use of U-500 Insulin with the Tandem X2 Pump with Control IQ (CIQ)

956-P: Successful Use of U-500 Insulin with the Tandem X2 Pump with Control IQ (CIQ)

Combination Use of U-500 Regular Insulin via Insulin Pump and Rapid-Acting U-100 Prandial Injections for Treatment of Pre-Existing Type 2 Diabetes in Pregnancy.

The high-dose large-volume insulin injections that may become necessary during pregnancy due to marked pregnancy-induced insulin resistance may result in suboptimal therapeutic effectiveness. Use of U-500 insulin, a concentrated insulin formulation, has been suggested during pregnancy. However, the pharmacokinetic properties of U-500 insulin monotherapy can impede achievement of strict pregnancy glycemic targets. We propose a novel regimen for treatment of severe pregnancy-induced insulin resistance that enables precise delivery of U-500 basal insulin therapy through continuous subcutaneous insulin infusion (CSII) while maintaining the desired kinetics of prandial rapid-acting U-100 insulin therapy. This combination approach, guided by continuous glucose monitoring data, enabled achievement of pregnancy glycemic targets while reducing basal insulin requirements by approximately one-third. We report our method for (1) conversion to U-500 insulin delivery through CSII during pregnancy and (2) conversion from U-500 basal insulin delivery through CSII to U-100 intravenous insulin infusion therapy at delivery, to offer clinicians who encounter similar challenging scenarios a novel approach to diabetes management during pregnancy in the setting of marked insulin resistance.

A multifaceted approach in leveraging electronic health record tools for safe inpatient use of concentrated U-500 insulin.

The Institute for Safe Medication Practices classifies subcutaneous insulin as a high-risk medication. Concentrated U-500 insulin carries additional risks in comparison to conventional U-100 insulin, as the 5-fold more concentrated nature of this product, limitations to insulin pen dosing, and various devices for dose measurement may lead to miscommunication of patient-reported doses, resulting in downstream errors in ordering, verification, or administration. We describe a multifaceted approach to leveraging technical tools within the electronic health record (EHR) for U-500 insulin use. At Cleveland Clinic, the U-500 insulin use process evolved in a number of phases using EHR tools. Phase 1 included new clinical decision support and documentation tools during order entry, including a customized alert that fired during order entry recommending that the prescriber order a consult with endocrinology and requiring the prescriber to provide the patient's home insulin measuring device and the source of the patient's reported home dose. In order verification, a customized alert fired directing the pharmacist to contact the patient or patient's nurse and validate the information provided by the prescriber. Phase 2 involved transitioning dispensing of patient-specific doses from tuberculin syringes to U-500 insulin syringes. Phase 3 transitioned to use of U-500 insulin pens and included automatic dose rounding of ordered doses down to the nearest 5 units, and an additional customized pharmacist alert intended for cost conservation was added to fire if the patient had a recent administration of U-500 insulin documented, directing the pharmacist to determine whether the nurse needed a new pen dispensed. Cleveland Clinic successfully implemented customized tools and processes within the EHR pertaining to the prescribing, verification, dispensing, and administration of U-500 insulin.

2195-PUB: Use of U500 Insulin in External Pump for Insulin-Resistant Diabetic Patients: A French Experience

Use of large insulin doses is more frequent in diabetes due to an increase in the prevalence of severe obesity worlwide. Insulin-associated treatments such as metformin or GLP-1 receptor agonists (GLP-1RA) can help and use of insulin concentrated at 500 IU/ml (U500) has been associated with an improve in glycemic control in previous studies including severe insulin resistant patients. We report our experience of U500 in subjects with high HbA1c despite insulin pump therapy (CSII) combined or not with metformin and/or GLP-1RA. Eighteen T2D and 3 T1D were studied (13M and 8F), age: 59.5 ± 9.6 years, diabetes duration : 18.8 ± 9.8 years. Eight subjects used metformin and 7 used GLP-1RA (5 used metformin and GLP-1RA). Treatment with U500 was carried out during a 5-day hospitalization. Metformin and/or GLP-1RA were continued or not during the follow-up according to the decision of the patient’s diabetologist. Mean duration of follow-up was 9 months. A decrease in HbA1c was found (initial vs. final) : 9.4 ± 1.2% vs. 8.5 ± 1.3% (p =0.05). No change was found for weight : 123.9 ± 26.4 kg vs. 121.0 ± 30.3 kg (NS), BMI : 41.5 ± 7.2 kg/m2 vs. 40.2 ± 7.3kg/m2 (NS), daily total insulin needs (U100 equivalent) : 198.4 ± 70.5 IU vs. 228 ± 121 IU (NS), basal needs : 81.8 ± 29.2 IU vs. 87 ± 36 IU (NS) and prandial needs : 116.5 ± 61.3 IU vs. 143 ± 110 IU (NS). No changes were found for lipidic parameters as total cholesterol (TC) : 1.85 ± 1.10 g/l vs. 1.80 ± 0.92 g/l (NS), HDL-C : 0.36 ± 0.08 g/l vs. 0.31 ± 0.06 g/l (NS), LDL-C : 0.83 ± 0.32 g/l vs. 0.71 ± 0.30 g/l (NS) and TG : 3.98 ± 7.56 g/l vs. 3.4 ± 5.3 g/l (NS). No change in use of metformine and/or GLP-1RA and no side effect were found during the follow-up. Conclusion: In our practice, use of U500 in insulin-resistant patients treated with CSII is well tolerated and is associated with a decrease in HbA1c despite no change in weight or daily insulin needs. Evolution of glycemic variability (including TIR and hypoglycemias) using continuous glucose monitoring is currently being analyzed. Disclosure Y. Oualit: None. D. Pâris: Board Member; Self; Novo Nordisk Inc. Consultant; Self; Eli Lilly and Company, Sanofi-Aventis. L. Kessler: Consultant; Self; Lilly Diabetes, Medtronic, Novartis Pharma K.K., Novo Nordisk A/S, Vertex Pharmaceuticals. T. Bahougne: None. N. Jeandidier: Consultant; Self; Sanofi-Aventis. Research Support; Self; Lilly Diabetes. L. Meyer: Board Member; Self; Abbott, Lilly Diabetes, Novo Nordisk A/S.

Case Series of U-500 Insulin Use in Adults With Type 2 Diabetes and Severe Insulin Resistance

ObjectivesSevere insulin resistance results in large volumes of insulin to achieve glycemic control. These large volumes can result in patient discomfort and decreased satisfaction. Using the more concentrated U-500 insulin provides a solution to this problem. This case series demonstrates real-world use of U-500 insulin in a Canadian population. MethodsSeventeen patients were identified to have been started on U-500 insulin at an endocrinology clinic in Vancouver, British Columbia, Canada. The retrospective chart review looked at patients’ characteristics before starting U-500 insulin and at their 1-year follow-up appointment. ResultsAt follow up, patients demonstrated improved glycated hemoglobin with a mean improvement of 1.6% at 1 year (p<0.05). There was a statistically significant increase in hypoglycemia (p<0.05), and, on average, patients gained 5.6 kg over the course of the year (p<0.05). There was no statistically significant change in number of units of insulin, injections, lipids, renal function or blood pressure. ConclusionsThe initiation of U-500 insulin results in improved glycemic control at the cost of increased hypoglycemia and weight gain.

1268-P: Evaluation of Inpatient Insulin Dose Requirements and Glycemic Control of Patients Using U-500 Regular Insulin Prior to Admission

Objective: Questions remain regarding the appropriate use of U-500 insulin particularly, in the hospital setting. The objective of this study was to evaluate the inpatient insulin dose requirements and glycemic control of patients using U-500 insulin prior to admission. Methods: A retrospective chart review of adult patients using U-500 insulin prior to admission to Beaumont Hospitals between March 2012 and July 2017 was conducted. Inpatient insulin dose requirements and glycemic control were compared between those who were continued on U-500 insulin and those transitioned to a U-100 insulin regimen. Results: A total of 95 patients were included in the study. Seventeen patients were continued on U-500 insulin while the remaining 78 received U-100 insulin during their inpatient stay. U-500 insulin group received significantly more units of insulin per day (181 units versus 99.65 units; p = 0.0048). However, the proportion of insulin administered inpatient relative to the prior to admission dose was similar between the two groups (59% in the U-500 group and 46% in U-100 group; p = 0.1344). Glycemic control was similar between the groups except for significantly more hypoglycemia events in the U-500 group compared to the U-100 group (p &amp;lt; 0.0001). When patients were further stratified by prior to admission dose or HbA1c, significantly more hypoglycemia was observed in the U-500 group with HbA1c &amp;lt; 8% and those with prior to admission dose between 300-600 units. Conclusions: Our retrospective review demonstrated that only very few patients were continued on a U-500 insulin regimen during their hospitalization. Inpatient use of U-500 insulin posed higher risk of hypoglycemia even when used at much lower doses than the established home regimen. Continued use of U-500 insulin in the hospital requires careful assessment of the risks and further investigation is needed to determine the appropriate dosing. Disclosure P. Sanaty Zadeh: None. M.F. Lutz: None. A.A. Feleke: None.

Glycemic Efficacy With U-500 Insulin in Pregnancy: A Retrospective Cross-Over Study [21K

INTRODUCTION: Pre-gestational diabetes, one of the most challenging complications of pregnancy, may require over 200 units per day in patients with severe insulin resistance, resulting in compliance and absorption issues. The purpose of this study was to determine if conversion to U-500 led to improved glycemic efficacy in pregnancies complicated by severe insulin resistance. METHODS: A retrospective review of pregnant patients managed with (Humulin R) U-500 from 2014 to 2018 was conducted. Maternal and neonatal demographics were abstracted. Primary objective was to compare fasting and postprandial glycemic efficacy, insulin injections per day and number of hypoglycemic episodes pre- and post- conversion to U-500 assessments. Wilcoxon two tailed signed ranks tests was used for the qualitative data analysis, P value &lt;.05 was considered statistically significant. RESULTS: Ten patients were identified. Mean gestational age was 24 weeks (16.2 to 33.4) and mean insulin dose was 301.8 U (64 to 522) at time of conversion to U-500. Post-conversion to U-500, a decrease in the percent-above-range fasting glucose levels (65.61% vs 51.56%, P=.047) and insulin injections per day (4.8 vs 3.5 P &lt;.01) was noted. An increase in percent-above-range postprandial glucose levels was noted post-conversion (45.26% vs 54.42%, P=.114). A trend towards decreased number of hypoglycemic episodes was noted (7.50 vs 3.80, P=.089). CONCLUSION: U-500 insulin use is associated with improved fasting glycemic efficacy with decreased number of injections per day in pregnancies complicated by pre-gestational diabetes. Additional experience with U-500 in pregnancy is warranted to determine its safety profile in terms of maternal and neonatal outcomes.

Treatment Approach to Patients With Severe Insulin Resistance.

In Brief Patients with severe insulin resistance require >2 units/kg of body weight or 200 units/day of insulin. Yet, many patients do not achieve glycemic targets despite using very high doses of insulin. Insulin can cause weight gain, which further contributes to worsening insulin resistance. This article describes the pharmacological options for managing patients with severe insulin resistance, including the use of U-500 insulin and newer agents in combination with insulin.

Medication safety strategies worth sharing with hospital pharmacists

Improving medication safety is at the forefront of most hospital pharmacists'minds. This complex issue has numerous facets and nuances,and nearly endless opportunities for pharmacists to jump in and makeinterventions that change hospital policy resulting in better, safer care.

Initiation of human regular U-500 insulin use is associated with improved glycemic control: a real-world US cohort study

AimDescribe the characteristics of patients initiating human regular U-500 insulin (U-500R) and their subsequent glycemic control in a real-world setting.MethodsUS Humedica electronic health record system data (July 2007–September 2011) were...

12-Year Cohort Study of U500 Insulin Use in Pregnant Women with Type 2 Diabetes Mellitus at BC Women's Hospital

12-Year Cohort Study of U500 Insulin Use in Pregnant Women with Type 2 Diabetes Mellitus at BC Women's Hospital

Abstracts from ATTD 20147th International Conference on AdvancedTechnologies &amp; Treatments for DiabetesVienna, Austria, February 5–8, 2014

Introduction: Currently measures of glycaemic variability (Standard Deviation, Mean and MAGE) all fail to fully highlight the extent of blood glucose variability so there is a need for improved measures of glycaemic variability. Aim: To utilise clinical data produced using CGMS to develop and validate a clinically-relevant novel measure of glycaemic variability and to use it to compare CSII with MDI. Methods: 20 participants (6 months pre and post CSII) with 24 hr CGM data sets were analysed. Glucose variability Rating (GVR) was calculated in three steps including change in sensor reading at 5 minute intervals which were then squared and av- eraged to obtain GVR (mmol/L) 2/hr. GVR was plotted, area under curve (AUC) calculated and pre vs. post-CSII GVR compared. Time series analysis was also investigated to try and identify specific periods with increased variability. A compari- son of the percentage change in GVR vs the change in HbA1c value in pre vs post-CSII was also analysed to identify correla- tion between these two measures. Results: GVR was applied to pre and post-CSII CGM data; 75% of participants showed < 20% reduction of GVR post-CSII vs. MDI. The group also showed a significant reduction in GVR (p < 0.003) post-CSII (vs MDI). Conclusions: Results indicate a reduction in glucose vari- ability with CSII and highlight the limitations of HbA1c, as well as the useful potential of GVR to highlight specific time periods where intervention is required to control blood glucose variability.

The use of U‐500 regular insulin in the management of patients with obesity and insulin resistance

The rise in prevalence of obesity and diabetes has created a challenge in managing increasing numbers of patients who require high doses of insulin. This article reviews the published literature on the properties of U-500 insulin and its use in clinical practice. U-500 insulin is likely to have a longer time to peak effect and a longer duration of action than similar doses of U-100 insulin. Evidence for its use in clinical practice rests on retrospective case series, which suggests that the use of U-500 insulin either by multiple daily injections or a continuous subcutaneous insulin infusion is effective in improving glycaemic control. To prevent insulin dosing and administration errors, great care must be taken in providing staff and patient education, and in developing policies for the management of patients on U-500 insulin who are admitted to hospital.

U-500 Insulin: Clinical Comments From the Experts

T wenty or thirty years ago, U-500 insulin was a product that, for the most part, sat in the corner and moldered. Relative to other pharmaceuticals, it was almost a curiosity. A patient treated with U-500 was a rarity and would likely end up with “grand rounds” status. Today, unfortunately, the picture is different. As the obesity and type 2 diabetes epidemics continue and we witness a relentless burgeoning of severely insulin-resistant patients, the use of U-500 insulin has escalated. Still, the use of U-500 insulin is not an everyday occurrence in most practices, and when it is used, health care providers must be vigilant in terms of both accurate prescribing and thorough patient education. Consistency and precision in the use of terminology surrounding the management of patients with U-500 insulin is obligatory. This journal recently published a “Practical Pointers” article (Valentine V: Don't resist using U-500 insulin and pramlintide for severe insulin resistance. Clinical Diabetes 30:80–84, 2012) and a corresponding patient information page (Good to Know: Using U-500 insulin. Clinical Diabetes 30:86, 2012) on the topic of U-500 insulin. These articles prompted both a letter to the editor from Dr. Robert C. Hood of …

The Effect of Long-Term Use of U-500 Insulin Via Continuous Subcutaneous Infusion on Durability of Glycemic Control and Weight in Obese, Insulin-Resistant Patients with Type 2 Diabetes

To evaluate the long-term efficacy and safety of U-500 insulin administered via continuous subcutaneous insulin infusion (CSII) in patients with insulin-resistant type 2 diabetes and high insulin requirements. We retrospectively reviewed the effects of U-500 insulin administered via CSII on durability of glycemic control (HbA1c), body weight, total daily insulin dose, and incidence of hypoglycemia in 59 patients with insulin-resistant type 2 diabetes (duration of treatment 1 to 9.5 years; mean treatment duration 49 months). All variables were analyzed by 1-way analysis of variance (ANOVA) from pre-U-500 baseline to time points from 3 to 114 months. After 3 months of U-500 insulin use, hemoglobin A1c dropped significantly from a mean baseline of 8.3% to a mean value of 7.3% (P = .003), and this improvement was sustained for over 66 months of use. There was no significant overall change in body weight or total daily insulin dose over time with the use of U-500 insulin. For those subjects who did gain weight, there was a parallel increase in insulin dose that correlated with weight gain. The overall incidence of severe hypoglycemia was low over the study period, with a mean occurrence of 0.1 episodes per patient per year. U-500 insulin is safe and effective for extended use (up to 9.5 years) in patients with insulin-resistant type 2 diabetes who require high insulin doses, and provides sustained glycemic control without causing excessive weight gain.

Use of U-500 Insulin in Pregnancy Is Intriguing, but Controlled Trials Are Needed

Use of U-500 Insulin in Pregnancy Is Intriguing, but Controlled Trials Are Needed

A New Challenge for Safe Ordering of U-500 Insulin: Electronic Medicine Reconciliation

T he transitioning of insulin orders for patients treated with U-500 regular human insulin from outpatient to inpatient settings and then back to the outpatient setting after hospital care is a safety challenge. Many hospitals follow the Institute of Safe Medical Practices (ISMP) guidelines for use of U-500 insulin.1 ISMP advises that the actual units and volume of insulin be used when ordering insulin. For example, when a patient is administered 0.15 ml of U-500 insulin, or 15 units on a U-100 syringe, ISMP advises that the actual number of units, “60 units of U-500 regular human insulin,” be part of the order. However, a neophyte to U-500 insulin could misinterpret the order for 60 units and draw up 60 units on a U-100 syringe, or 0.6 ml of U-500 insulin. This would result in an overdose of 300 actual units of insulin. Many institutions require that all doses of U-500 insulin be drawn up by a pharmacist to prevent this type of error. This following case demonstrates a new potential source of error associated with the use of electronic medicine reconciliation at discharge. J.J., a …

Clinical Experience with U500 Insulin: Risks and Benefits

To describe our clinical experience with U500 insulin in insulin-resistant patients, including change in glucose control, body weight, insulin dose, and hypoglycemic episodes. In September 2010, we undertook a retrospective chart review of patients who had U500 insulin in their medication list in the preceding 2 years who were treated in the endocrinology section at Dartmouth Hitchcock Medical Center. Glycosylated hemoglobin (A1C), body weight, and insulin dosage were documented before U500 insulin introduction, after 6 months of U500 insulin use, and at the last clinic visit when the patient was still taking U500 insulin. Hypoglycemic episodes and number of daily injections were recorded. Records of 53 patients were analyzed, one of the largest reports of U500 insulin use published to date. The mean A1C level decreased from 10.1% before U500 insulin was initiated to 9.1% after 6 months of U500 use to 8.6% at the last follow-up visit (mean follow-up was 36.6 ± 24 months). At the last charted visit, body weight increased by a mean of 6.8 kg and insulin dosage increased by a mean of 0.44 units/kg. We observed a significant increase in the number of nonsevere hypoglycemic episodes and a decrease in the number of daily injections. Patients with uncontrolled, severely insulin-resistant diabetes can be satisfactorily treated with U500 insulin with the potential to improve glycemic control. An increase in body weight, insulin dosage, and the number of nonsevere hypoglycemic episodes was observed.

Durability of glycemic control using U-500 insulin

Previous short-term studies evaluating U-500 insulin have reported improvements in glycemic control but with significant weight gain. This study was performed to examine the glycemic durability of U-500 insulin in highly insulin resistant subjects, and to determine if weight gain was continuous with use. Patients using U-500 insulin provided consent for chart reviews for up to 3 years prior to and 3 years after use of U-500 insulin. Charts were reviewed for physical and metabolic data from 53 subjects using U-500 insulin of which 20 used U-500 insulin for 3 years. Use of U-500 insulin led to an approximate 1% decrease in HbA1c within 3–6 months of use which was sustained for up to 3 years. Patients required increased insulin doses (by ∼80%) over the first 6–12 months with a corresponding weight gain (∼10lbs) and a spike in hypoglycemia symptoms, but then insulin doses and body weight, as well as glycemic control and hypoglycemic symptoms, stabilized over subsequent follow up. Use of U-500 insulin in a clinical diabetes practice leads to sustained improvements in glycemic control following a period of insulin titration and weight gain. Despite the weight gain, glycemic control was sustained for up to 3 years.

Safety and Effectiveness of U‐500 Insulin Therapy in Patients with Insulin‐Resistant Type 2 Diabetes Mellitus

To assess the safety and effectiveness of highly concentrated U-500 regular insulin in patients with insulin-resistant type 2 diabetes mellitus who were switched from U-100 insulin. Retrospective cohort study. Outpatient diabetes management clinic. Twenty-one adults with poorly controlled type 2 diabetes and insulin resistance who were referred to the clinic between July 1, 2007, and June 30, 2008, and whose therapy was changed from large doses of U-100 insulin to U-500 insulin. Demographic and clinical data were collected through a computerized medical record system. Insulin resistance was defined as a requirement of more than 200 units/day of insulin and more than 100 units/injection. The primary outcome was the change in hemoglobin A(1c) (A1C) after switching from any type of U-100 insulin to stabilization with U-500 highly concentrated regular insulin. Secondary outcomes were the changes in number of daily insulin injections, daily insulin dose, and body weight. With use of U-500 insulin, patients were able to achieve an average reduction in A1C of 1.7% (p<0.001). The mean number of daily injections decreased from 4.3 with U-100 insulin to 2.7 after using U-500 insulin (p<0.001), but changes in body weight after the change in insulin were not statistically significant (279.8 vs 279.2 lbs, p=0.429). No patient discontinued U-500 insulin during the study, and none experienced hypoglycemia severe enough to require the assistance of another individual. In patients with insulin-resistant diabetes who have requirements of more than 200 units/day or 100 units/injection, use of U-500 regular insulin provided the same or better glucose control compared with U-100 insulin, with fewer daily injections and reduced injection volume. Although this drug represents an excellent treatment option, its safe use requires an experienced physician, a motivated and cooperative patient, and a dynamic diabetes management team.