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CMAJ : Canadian Medical Association... Feb 1998To review the available literature on the new insulin analogue insulin lispro and provide information on its efficacy, indications for use and contraindications. (Review)
Review
OBJECTIVE
To review the available literature on the new insulin analogue insulin lispro and provide information on its efficacy, indications for use and contraindications.
DATA SOURCES
MEDLINE searches were made for articles published from 1966 to 1996 using the indexing term "lispro", "Humalog" and "insulin analogs".
STUDY SELECTION
About 30 studies and review articles were selected based on their relevance to the stated objective. These were critically appraised for the purpose of writing the review article so that it would be relevant to general practitioners, internists and nurse educators.
DATA SYNTHESIS
The therapeutic challenge when treating diabetic patients is to bring the blood glucose level into as normal a range as possible, with minimal hypoglycemia and hyperinsulinemia. Insulin lispro has a much faster, higher and shorter-lasting peak serum insulin level than regular human insulin, thus mimicking physiologic secretion of insulin more closely. As a result, there is improvement in postprandial blood glucose levels and decreased episodes of hypoglycemia, with no change in the hemoglobin A1c (HgbA1c) level. The ability to inject insulin lispro immediately before the meal allows greater flexibility of lifestyle. Compared with regular insulin, insulin lispro is associated with a lower risk of hypoglycemia with exercise several hours after a meal. It is therefore most useful for the motivated, compliant diabetic patient who would like to achieve a better hypoglycemia-HgbA1c ratio as well as for patients desiring further flexibility with premeal insulin injections. Use of insulin lispro has been shown to improve HgbA1c levels in patients using insulin pumps. It is well tolerated, and therapy is often continued after studies are completed. Further study is needed to establish optimal basal regimens.
Topics: Blood Glucose; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Patient Compliance; Patient Selection; Research Design
PubMed: 9627564
DOI: No ID Found -
Frontiers in Pharmacology 2023Type 1 diabetes is characterized by insulin deficiency, and treatment is to supply insulin mimicking the physiological endogenous insulin secretion. Since its discovery,... (Review)
Review
Type 1 diabetes is characterized by insulin deficiency, and treatment is to supply insulin mimicking the physiological endogenous insulin secretion. Since its discovery, insulin therapy has evolved, and since the 1990s, an increasing number of insulin analogs with various pharmacokinetic and pharmacodynamic profiles have become available. Despite the improvement of insulin therapy, hypoglycemia remains the main side effect and is a daily concern for many people with diabetes and their families. A proportion of people with type 1 diabetes are at increased risk of hypoglycemia and experience recurring episodes. When designing insulin trials, this group of people is most often excluded in order to reduce the risk of adverse study outcomes, even though it may be the group that may benefit the most from treatment with new insulins. The results of the phase III trials, therefore, underestimate the clinical impact and pharmacoeconomic effect of the implementation of new insulins in the broader type 1 diabetes population. This paper reviews the four insulin trials that include people at increased risk of hypoglycemia. In general, the studies confirm the results from phase III trials in terms of similar reduction and maintenance of HbA1c, as well as relative rate reductions of hypoglycemia. However, the absolute treatment differences in the reduction of hypoglycemia are even greater in the trials, including people at high risk of hypoglycemia. This emphasizes the importance of including people at high risk of hypoglycemia to assess the full clinical and pharmacoeconomic benefit of new insulins.
PubMed: 38089060
DOI: 10.3389/fphar.2023.1301931 -
Diabetes Therapy : Research, Treatment... Aug 2022Ultra-rapid lispro (URLi) is a new prandial insulin lispro formulation. In the PRONTO-T2D study, URLi, in a basal-bolus regimen with glargine or degludec, was...
INTRODUCTION
Ultra-rapid lispro (URLi) is a new prandial insulin lispro formulation. In the PRONTO-T2D study, URLi, in a basal-bolus regimen with glargine or degludec, was non-inferior to lispro (Humalog) for HbA1c reduction and superior for postprandial glucose (PPG) control. We evaluated the efficacy and safety of URLi compared to lispro in younger versus older patients in PRONTO-T2D.
METHODS
PRONTO-T2D was a phase 3, 26-week, double-blind, treat-to-target study in people with type 2 diabetes. In this sub-group analysis, we compared URLi to lispro on the change from baseline in HbA1c and rate of level 2 hypoglycemia (< 54 mg/dl) in patients aged < 65 (N = 406) and ≥ 65 years (N = 267).
RESULTS
At baseline, patients < 65 versus ≥ 65 years had mean age of 54.9 versus 69.2 years and duration of diabetes 14.6 versus 19.4 years. Mean HbA1c at screening and randomization was 8.35 and 7.34%, respectively, in patients < 65 years, and 8.21 and 7.23%, respectively, in patients ≥ 65 years. At endpoint, mean HbA1c with URLi versus lispro was 6.92 versus 6.90%, respectively, in patients < 65 years and 6.89 versus 6.79%, respectively, in patients ≥ 65 years. URLi significantly reduced 1- and 2-h PPG excursions with a standardized meal test in both age groups: between-treatment differences at 1-h postmeal for younger and older patients was - 9.8 and - 15.1 mg/dl, respectively; and at 2-h postmeal, - 18.7 and - 15.1 mg/dl, respectively, all p < 0.05. Severe and nocturnal hypoglycemia were similar between groups. The relative rate (URLi/Humalog) of level 2 hypoglycemia was lower in older versus younger patients, with a significant treatment-by-age interaction observed. No differential treatment effects were noted for insulin dose, weight, and fasting and maximum glucose after the meal test.
CONCLUSIONS
URLi, in a basal-bolus regimen, resulted in endpoint HbA1c < 7% and significantly lower PPG excursions compared to lispro in both age groups, with reduced level 2 hypoglycemia in older versus younger patients.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03214380.
PubMed: 35781789
DOI: 10.1007/s13300-022-01290-4 -
Indian Journal of Endocrinology and... 2016This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of...
This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage.
PubMed: 27186563
DOI: 10.4103/2230-8210.180003 -
Journal of Diabetes Investigation Mar 2022Subcutaneous insulin resistance syndrome is a rare condition that causes difficulty in glycemic control due to severe resistance to subcutaneous insulin injections. We...
Subcutaneous insulin resistance syndrome is a rare condition that causes difficulty in glycemic control due to severe resistance to subcutaneous insulin injections. We herein present a case of a 40-year-old woman with type 2 diabetes mellitus who had been diagnosed with subcutaneous insulin resistance syndrome since the age of 29 years, and had been persistently treated with continuous subcutaneous insulin infusion using a mixture of insulin lispro and heparin. The patient was switched from insulin lispro plus heparin to ultra-rapid insulin lispro; given that it contains treprostinil and citrate, it is expected to have similar effects as heparin, and shows similar glucose-lowering effects and insulin absorption. Our results suggest that treatment with ultra-rapid insulin lispro is effective for subcutaneous insulin resistance syndrome.
Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin Resistance
PubMed: 34510782
DOI: 10.1111/jdi.13667 -
Diabetes/metabolism Research and Reviews Jul 2007The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence but not completely suppressed the occurrence... (Review)
Review
The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence but not completely suppressed the occurrence of insulin allergy manifestations. Advances in technologies concerning the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion (CSII), and the use of insulin analogues, resulting from the alteration in the amino acid sequence of the native insulin molecule, may influence the immunogenicity and antigenicity of native insulin. Instead of increasing allergy reactions, CSII has been reported to represent a successful alternative treatment in diabetic patients presenting local or generalized allergy to insulin or other components (zinc, protamine) of conventional treatment. Most recent reports concern CSII-treated patients using short-acting insulin analogues (essentially insulin lispro), although the precise role of these insulin analogues remains unclear as allergy to them has also been described. Finally, data on antigenicity and immunogenicity of long-acting insulin analogues (glargine, detemir), which may mimic the basal insulin delivery with CSII, remain scarce at present.
Topics: Diabetes Mellitus; Drug Hypersensitivity; Humans; Hypoglycemic Agents; Insulin; Insulin Infusion Systems
PubMed: 17216593
DOI: 10.1002/dmrr.714 -
Vascular Health and Risk Management 2009The incidence of gestational diabetes is increasing. As gestational diabetes is associated with adverse pregnancy outcomes, and has long-term implications for both... (Review)
Review
The incidence of gestational diabetes is increasing. As gestational diabetes is associated with adverse pregnancy outcomes, and has long-term implications for both mother and child, it is important that it is recognized and appropriately managed. This review will examine the pharmacological options for the management of gestational diabetes, as well as the evidence for blood glucose monitoring, dietary and exercise therapy. The medical management of gestational diabetes is still evolving, and recent randomized controlled trials have added considerably to our knowledge in this area. As insulin therapy is effective and safe, it is considered the gold standard of pharmacotherapy for gestational diabetes, against which other treatments have been compared. The current experience is that the short acting insulin analogs lispro and aspart are safe, but there are only limited data to support the use of long acting insulin analogs. There are randomized controlled trials which have demonstrated efficacy of the oral agents glyburide and metformin. Whilst short-term data have not demonstrated adverse effects of glyburide and metformin on the fetus, and they are increasingly being used in pregnancy, there remain long-term concerns regarding their potential for harm.
Topics: Administration, Oral; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes, Gestational; Drug Administration Schedule; Exercise; Female; Fetus; Glyburide; Humans; Hypoglycemic Agents; Injections; Insulin; Metformin; Postpartum Period; Pregnancy; Pregnancy Outcome; Treatment Outcome
PubMed: 19436673
DOI: 10.2147/vhrm.s3405 -
Journal of Comparative Effectiveness... Jan 2021To compare safety (immunogenicity) and efficacy of a biosimilar insulin GP-Lis25 and a reference insulin Ly-Lis25 (Humalog Mix 25) in Type 2 diabetes mellitus (T2D)... (Randomized Controlled Trial)
Randomized Controlled Trial
To compare safety (immunogenicity) and efficacy of a biosimilar insulin GP-Lis25 and a reference insulin Ly-Lis25 (Humalog Mix 25) in Type 2 diabetes mellitus (T2D) patients. This randomized open-label, 26-week clinical trial enrolled 210 T2D patients, randomized 1:1 to twice-daily GP-Lis25 or Ly-Lis25. The primary end point was immune response at 26th week. Noninferiority margin for HbA1c was 0.4%. Immune response frequency was similar in GP-Lis25 and Ly-Lis25 groups both at week 12 (p = 0.651) and 26 (p = 0.164). The difference of HbA1c change at week 26 was (95% CI) 0.01 (-0.27-0.28)%. Fasting plasma glucose, seven-point glucose profile and insulin dose were similar between groups. Safety did not differ between groups. GP-Lis25 and Ly-Lis25 demonstrated similar safety and efficacy. ClincalTrials.gov identifier: NCT04023344.
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro
PubMed: 33355484
DOI: 10.2217/cer-2020-0064 -
Diabetes Technology & Therapeutics Oct 2022To evaluate the insulin-only configuration of the iLet bionic pancreas (BP) in youth 6-17 years old with type 1 diabetes (T1D). In this multicenter, randomized,... (Randomized Controlled Trial)
Randomized Controlled Trial
To evaluate the insulin-only configuration of the iLet bionic pancreas (BP) in youth 6-17 years old with type 1 diabetes (T1D). In this multicenter, randomized, controlled trial, 165 youth with T1D (6-17 years old; baseline HbA1c 5.8%-12.2%; 35% using multiple daily injections, 36% using an insulin pump without automation, 4% using an insulin pump with low glucose suspend, and 25% using a hybrid closed-loop system before the study) were randomly assigned 2:1 to use BP ( = 112) with insulin aspart or insulin lispro (BP group) or to a control group ( = 53) using their personal standard care insulin delivery (SC group) plus real-time continuous glucose monitoring (CGM). The primary outcome was HbA1c at 13 weeks. Mean HbA1c decreased from 8.1% ± 1.2% at baseline to 7.5% ± 0.7% at 13 weeks with BP versus 7.8% ± 1.1% at both baseline and 13 weeks with SC (adjusted difference = -0.5%, 95% CI -0.7% to -0.2%, < 0.001). Participants with baseline HbA1c ≥9.0% ( = 34) decreased mean HbA1c from 9.7% ± 0.8% to 7.9% ± 0.6% after 13 weeks with BP compared with 9.7% ± 0.5% to 9.8% ± 0.8% with SC. Over 13 weeks, mean time in range (TIR) 70-180 mg/dL increased by 10% (2.4 h per day) and mean CGM glucose was reduced by 15 mg/dL with BP compared with SC ( < 0.001). Analyses of time >180 mg/dL, time >250 mg/dL, and standard deviation of CGM glucose favored BP ( < 0.001). Time <54 mg/dL was low at baseline (median 0.2%) and not significantly different between groups over 13 weeks ( = 0.24). A severe hypoglycemia event occurred in 3 (2.7%) participants in the BP group and in 1 (1.9%) in the SC group. In youth 6-17 years old with T1D, use of insulin-only configuration of BP improved HbA1c, TIR, and hyperglycemic metrics without increasing CGM-measured hypoglycemia compared with standard of care. Improvement in glycemic metrics was most pronounced in participants with high baseline HbA1c levels. clinicaltrials.gov; NCT04200313.
Topics: Adolescent; Bionics; Blood Glucose; Blood Glucose Self-Monitoring; Child; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Infusion Systems; Insulin Lispro; Insulin, Regular, Human; Pancreas
PubMed: 36173237
DOI: 10.1089/dia.2022.0201.pub -
Clinical Pharmacokinetics Nov 2021Ultra rapid lispro (URLi) is a novel insulin lispro formulation developed to more closely match physiological insulin secretion and improve postprandial glucose control.... (Meta-Analysis)
Meta-Analysis
Ultra Rapid Lispro (URLi) Accelerates Insulin Lispro Absorption and Insulin Action vs Humalog Consistently Across Study Populations: A Pooled Analysis of Pharmacokinetic and Glucodynamic Data.
BACKGROUND AND OBJECTIVE
Ultra rapid lispro (URLi) is a novel insulin lispro formulation developed to more closely match physiological insulin secretion and improve postprandial glucose control. This pooled analysis compared the pharmacokinetics and glucodynamics between URLi and Humalog in healthy subjects and patients with type 1 or type 2 diabetes mellitus.
METHODS
The analysis included four randomized, double-blind, crossover, single-dose studies (healthy subjects [n = 74], patients with type 1 diabetes [n = 78], and type 2 diabetes [n = 38]) evaluating subcutaneous doses of 7, 15, or 30 U of URLi and Humalog during an 8- to 10-h euglycemic clamp procedure.
RESULTS
The pooled analysis showed an ~ 5-min faster onset of appearance, an ~8-fold greater exposure in the first 15 min, a 43% reduction in exposure beyond 3 h, and a 68-min shorter exposure duration with URLi vs Humalog across all study populations and dose range. Compared with Humalog, URLi had a 10-min faster onset of action, a 3-fold greater insulin action in the first 30 min, a 35% reduction in insulin action beyond 4 h, and a 44-min shorter duration of action across all populations and dose range. Overall exposure and insulin action were similar between URLi and Humalog for each dose level and study population.
CONCLUSIONS
Across the studied populations and dose range, URLi consistently demonstrated a faster absorption, reduced late exposure, and overall shorter exposure duration compared with Humalog. Similarly, URLi demonstrated earlier insulin action while reducing late insulin action and shorter insulin action compared with Humalog across the study populations and dose range.
CLINICAL TRIAL REGISTRATION
NCT02942654 (registered: 21 October, 2016), NCT03286751 (registered: 15 September, 2017), NCT03166124 (registered: 23 May, 2017), and NCT03305822 (registered: 5 October, 2017).
Topics: Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Randomized Controlled Trials as Topic
PubMed: 34041713
DOI: 10.1007/s40262-021-01030-0