987-P: Efficacy and Safety Comparison between U-100 Human Regular Insulin and Rapid-Acting Insulin When Delivered by V-Go Wearable Insulin Delivery in an Older Type 2 Diabetes Population

Abstract Introduction: Increasing insulin prices have led to a renewed debate to determine if Rapid Acting Insulin (RAI) analogs offer an advantage over less expensive Regular Human Insulins (RHI). The steep increase in the cost of RAI has led to rationing of insulin or the total discontinuance of therapy by many patients due to cost. For many, RHI provides a more affordable option for insulin therapy when compared to RAI, especially if the limitations of the insulin profile can be overcome by delivering RHI through continuous subcutaneous insulin infusion (CSII) using a wearable insulin delivery device. To our knowledge, no data exists in a type 2 diabetes (T2D) population comparing RAI to RHI when delivered via CSII. Methods: This 14 week multi-center prospective, randomized parallel, non-inferiority study in a T2D population compared the efficacy and safety of RAI versus RHI when delivered by V-Go®, a 24-hr wearable patch-like insulin delivery device that provides a preset continuous basal rate of insulin and on-demand bolus dosing. This study was conducted in a real-world practice setting under usual standard of care. Glucose lowering agents were to remain stable unless removal warranted due to documented clinically significant hypoglycemia and the only specific guidance for insulin titration was to down-titrate if blood glucose levels were consistently lower than target range. Patients administering RAI with V-Go were randomized 1:1 to continue RAI or to switch to RHI. Primary endpoint assessed non-inferiority for the between group net difference in HbA1c derived from a mixed model analysis. Between group differences from baseline for insulin total daily dose (TDD) and hypoglycemia (based on 7 point glucose profiles) were evaluated as secondary endpoints. Results: One hundred thirteen patients (59 RHI and 54 RAI) were evaluated. Baseline characteristics were similar between cohorts. The mean change in HbA1c with RHI was -0.60% from a baseline of 8.41% vs -0.38% from a baseline of 8.33% with RAI (estimated treatment difference [ETD]: -0.22%; 95% confidence interval [CI] -0.67% to 0.22%; non-inferiority margin<0.4% and p=0.007). The mean change in TDD with RHI was 0.8 U/day from a baseline of 61.0 U/day vs 1.8 U/day from a baseline of 61.3 U/day with RAI (ETD: -1.04 U/day; 95% CI: -3.18 U/day to 1.11 U/day; p=0.92). The absolute change in percent of patients reporting hypoglycemia (≤ 70 mg/dL) from pre-randomization to post-randomization was +5.08% with RHI vs + 5.56% with RAI (ETD: -0.48%; 95% CI: -10.6% to 9.1%; p=0.91). Severe hypoglycemia was not reported in either cohort. Conclusion: Patients with T2D administering RAI with V-Go can safely switch to RHI maintaining similar glycemic control.

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Efficacy, safety and cost-effectiveness comparison between U-100 human regular insulin and rapid acting insulin when delivered by V-Go wearable insulin delivery device in type 2 diabetes

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001832 ◽

2020 ◽

Vol 8 (2) ◽

pp. e001832

Author(s):

Pablo F Mora ◽

David R Sutton ◽

Ashwini Gore ◽

Bantwal Baliga ◽

Rebecca F Goldfaden ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cost Savings ◽

Insulin Delivery ◽

Regular Insulin ◽

Pharmacy Cost ◽

Delivery Device ◽

Primary Analysis ◽

Open Label ◽

Acting Insulin

IntroductionWe compared the efficacy and safety of human regular insulin (HRI) versus rapid-acting insulin (RAI) in a type 2 diabetes population already using the V-Go insulin delivery device.Research design and methodsThis was a 14-week, multicenter, randomized, open-label, parallel-group, phase IV, non-inferiority study. Patients ≥21years of age, with inadequately controlled type 2 diabetes who were currently using the V-Go insulin delivery system with RAI, with glycated hemoglobin (HbA1c) ≥6.5% (≥48 mmol/L) to ≤12.5% (≤108 mmol/L) were randomized 1:1 to RAI continuation or switch to HRI. The primary outcome was estimated treatment difference (ETD) in HbA1c least-squares mean change from baseline at 14 weeks (prespecified non-inferiority hypothesis with 95% CI upper limit <0.4%). Primary analysis was by per protocol (PP); safety analysis was by intention to treat.ResultsWe randomized 136 patients to continued RAI treatment (n=67) or HRI (n=69); 113 patients were included in the PP analysis (RAI, n=54; HRI, n=59). Mean change in HbA1c from baseline to study end was −0.60±1.1% (95% CI −0.90 to –0.29); −6.6±12.0 mmol/mol (95% CI −9.8 to −3.2) with HRI treatment and −0.38±1.3% (95% CI −0.70 to –0.05); −4.2±14.2 mmol/mol (95% CI −7.7 to −0.5) with RAI treatment, with ETD of −0.22% (95% CI −0.67 to 0.22); −2.4 mmol/mol (95% CI −7.3 to 2.4), p=0.007, confirming non-inferiority of HRI to RAI. No between-group differences in changes in total daily insulin doses, number of hypoglycemic values (≤70 mg/dL (≤39 mmol/L) or body weight were observed. No severe hypoglycemic events were reported. Direct pharmacy cost savings (−US$265.85; 95% CI −US$288.60 to −US$243.11; p<0.0001) were observed with HRI treatment.ConclusionsIndividuals with type 2 diabetes requiring insulin can be treated with V-Go wearable insulin delivery device using HRI, safely and effectively, and potentially at a much lower cost compared with RAI, which can lead to improved access to insulin therapy for these individuals.Trial registration numberNCT03495908.

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1005-P: Comparison of Hypoglycemia Safety between U-100 Human Regular Insulin and Rapid-Acting Insulin Delivered By V-Go Wearable Insulin Delivery in Type 2 Diabetes

Diabetes ◽

10.2337/db20-1005-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 1005-P

Author(s):

PABLO F. MORA ◽

DAVID R. SUTTON ◽

ASHWINI GORE ◽

BANTWAL BALIGA ◽

REBECCA F. GOLDFADEN ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Delivery ◽

Regular Insulin ◽

Acting Insulin

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Insulin U-500, the Practical Solution for the treatment of Patients with High Insulin Requirements

Current Diabetes Reviews ◽

10.2174/1573399816666200408084614 ◽

2020 ◽

Vol 17 (1) ◽

pp. 26-29

Author(s):

Nasser Mikhail

Keyword(s):

Type 2 Diabetes ◽

Randomized Trials ◽

Regular Insulin ◽

Injection Pain ◽

Regular Human Insulin ◽

Efficacy And Safety ◽

Insulin Requirements ◽

High Insulin

Background: Human regular insulin 500 (U-500) is 5 five times more concentrated than the traditional regular human insulin (U-100). Thus, every 1 ml of U-500 contains 500 units of insulin as opposed to 100 units/ml with most types of insulin. Methods: Review of all the relevant clinical studies related to insulin U-500 until February 12, 2020. Results: Insulin U-500 is indicated in patients with type 2 diabetes who require more than 200 units of insulin per day. Insulin U-500 has both prandial and basal actions, and can be injected as monotherapy in a convenient twice-daily regimen. Available data suggest that insulin U-500 is effective, associated with better compliance, and decreased injection pain compared with non-concentrated insulins. Its main limitations are hypoglycemia and weight gain, and the possibility of dosing errors. Conclusions: Overall, insulin U-500 is an effective and safe treatment for patients with type 2 diabetes and insulin resistance. Randomized trials are needed to compare the long-term efficacy and safety of insulin U-500 with other forms of insulin regimens.

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Comparative efficacy and safety of long-acting insulin analogs in patients with type 2 diabetes failing on oral therapy: Systemic review and meta-analyses

Journal of Diabetes Investigation ◽

10.1111/j.2040-1124.2011.00187.x ◽

2011 ◽

Vol 3 (3) ◽

pp. 283-293 ◽

Cited By ~ 4

Author(s):

Yan Bi ◽

Xiubin Li ◽

Daizhi Yang ◽

Yuantao Hao ◽

Hua Liang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Oral Therapy ◽

Systemic Review ◽

Efficacy And Safety ◽

Insulin Analogs ◽

Comparative Efficacy ◽

Acting Insulin ◽

Long Acting ◽

Meta Analyses

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Inhaled Insulin: Exubera

Annals of Pharmacotherapy ◽

10.1345/aph.1e522 ◽

2005 ◽

Vol 39 (5) ◽

pp. 843-853 ◽

Cited By ~ 22

Author(s):

Peggy Soule Odegard ◽

Kam L Capoccia

Keyword(s):

Type 2 Diabetes ◽

Patient Satisfaction ◽

Regular Insulin ◽

Insulin Analog ◽

Subcutaneous Insulin ◽

Inhaled Insulin ◽

Acting Insulin ◽

Long Acting

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of Exubera, a novel, dry-powder formulation of insulin for inhalation, and describe patient satisfaction and quality-of-life data. DATA SOURCES: A MEDLINE search (1966–November 2004) was conducted using the key words inhaled insulin and Exubera for clinical trials limited to human research published in English. BIOSIS Previews and the American Diabetes Association Scientific Abstracts were used for published abstract information. STUDY SELECTION AND DATA EXTRACTION: All available human studies of Exubera were selected for review. References of identified articles were used for additional citations. DATA SYNTHESIS: Exubera is a rapid-acting insulin administered by oral inhalation before meals with long-acting insulin administered subcutaneously once or twice daily for type 1 or 2 diabetes mellitus. Exubera provides similar efficacy and improved patient satisfaction compared with standard subcutaneous insulin therapy (ie, NPH twice daily with regular insulin before meals). Efficacy has also been demonstrated for Exubera when used as adjunctive therapy with oral medications for type 2 diabetes. The onset of Exubera is more rapid and its duration of action is similar to that of regular insulin. To date, Exubera administered before meals with a once-daily long-acting subcutaneous insulin (usually Ultralente) has been compared with standard subcutaneous NPH/regular insulin regimens. Comparison of premeal Exubera plus a basal long-acting insulin analog (eg, glargine) with a regimen of premeal subcutaneous rapid-acting insulin analog (eg, lispro or aspart) plus a basal long-acting insulin analog (eg, glargine) is needed to fully evaluate Exubera. Pulmonary safety appears to be maintained for up to 4 years, although there are no data, as of this writing, on the use of this agent in patients with pulmonary conditions. CONCLUSIONS: Exubera is an effective inhaled insulin for preprandial use in type 1 or 2 diabetes. Improved patient satisfaction over injected insulin increases its potential for use earlier in the treatment of type 2 diabetes.

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Efficacy And Safety of Antidiabetic Drugs Available on Brazilian Public Health System (Sus) – Regular Insulin, Nph Insulin, Metformin, Glibenclamide And Gliclazide – In Treatment of Type 2 Diabetes (T2dm) - Systematic Review And Meta-Analysis

Value in Health ◽

10.1016/j.jval.2015.09.499 ◽

2015 ◽

Vol 18 (7) ◽

pp. A862 ◽

Cited By ~ 1

Author(s):

J Alvares ◽

VE Araujo ◽

JB Izidoro ◽

LM Diniz ◽

RC Nascimento ◽

...

Keyword(s):

Public Health ◽

Systematic Review ◽

Type 2 Diabetes ◽

Health System ◽

Public Health System ◽

Meta Analysis ◽

Regular Insulin ◽

Efficacy And Safety ◽

Nph Insulin

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Long-acting insulin analogue in the treatment of type 2 diabetes mellitus: emphasis on proven efficacy and safety

Medical Council ◽

10.21518/2079-701x-2021-12-246-255 ◽

2021 ◽

pp. 246-255

Author(s):

E. V. Biryukova ◽

M. V. Shinkin ◽

O. M. Mikheeva

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Insulin Glargine ◽

Phase Iii ◽

Efficacy And Safety ◽

Acting Insulin ◽

Modern Analogue ◽

Long Acting

In time, prescription of insulin therapy (IT) becomes inevitable for many patients with type 2 diabetes mellitus (DM) to achieve and maintain the target hypoglycemic range.According to the current guidelines, the addition of basal insulin to glucose-lowering therapy in patients with insufficient control of type 2 diabetes, gradual titration of its dose in accordance with a fasting blood glucose level is an effective and safe method for initiating IT. The properties of modern long-acting insulin analogues are considered. Glargine 300 U/ml is a modern analogue of long-acting insulin that is intended to be used once a day. The glargine molecule forms the basis of the drug. Increasing the concentration of glargine per volume unit and formation of a smaller subcutaneous depot led to a change in the pharmacokinetic properties of the drug. Glargine 300 IU/ml provides a more stable, long-term, predictable action with low glycemic variability as compared with glargine 100 IU/ml, which reduces the risk of hypoglycemia. The sugar-reducing efficacy and safety of insulin glargine 300 U/ml as evidenced by the findings of the international clinical phase III EDITION studies are discussed. Insulin glargine 300 U/ml showed a similar decrease in HbA1c levels compared to insulin glargine 100 U/ml with an improved safety profile (lower risk of developing episodes of confirmed or severe hypoglycemia at all times of the day, including the nighttime) and a less pronounced effect on the body weight of patients with type 2 diabetes. The efficacy and safety of the use of glargine 300 U/ml has been confirmed in type 2 diabetes patients with chronic kidney disease and the elderly. In the BRIGHT study, glargine 300 U/ml showed comparable glycemic control when it is being compared.

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