Investigational new insulin glargine 300 U/ml has the same metabolism as insulin glargine 100 U/ml

Steinstraesser, A.; Schmidt, Ronald; Bergmann, Karin; Dahmen, Raphael; Becker, R. H. A.

doi:10.1111/dom.12283

Cited by 100 publications

(111 citation statements)

References 11 publications

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“…A -Gly-human insulin (metabolite M1) after injection with each formulation (25). No evidence of increased injection-site problems or other AEs appeared in this study, but more participant-years of observation will be needed to confirm longterm safety.…”

Section: Discussionmentioning

confidence: 67%

New Insulin Glargine 300 Units/mL Versus Glargine 100 Units/mL in People With Type 2 Diabetes Using Basal and Mealtime Insulin: Glucose Control and Hypoglycemia in a 6-Month Randomized Controlled Trial (EDITION 1)

et al. 2014

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OBJECTIVETo compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes on basal insulin ( ‡42 units/day) plus mealtime insulin. RESEARCH DESIGN AND METHODSEDITION 1 (NCT01499082) was a 6-month, multinational, open-label, parallelgroup study. Adults with glycated hemoglobin A 1c (HbA 1c ) 7.0-10.0% (53-86 mmol/mol) were randomized to Gla-300 or Gla-100 once daily with dose titration seeking fasting plasma glucose 4.4-5.6 mmol/L. Primary end point was HbA 1c change from baseline; main secondary end point was percentage of participants with one or more confirmed (£3.9 mmol/L) or severe nocturnal hypoglycemia from week 9 to month 6. RESULTSParticipants (n = 807) had mean age 60 years, diabetes duration 16 years, BMI 36.6 kg/m 2 , and HbA 1c 8.15% (65.6 mmol/mol). HbA 1c reduction was equivalent between regimens; least squares mean difference -0.00% (95% CI -0.11 to 0.11) (-0.00 mmol/mol [-1.2 to 1.2]). Fewer participants reported one or more confirmed (£3.9 mmol/L) or severe nocturnal hypoglycemic events between week 9 and month 6 with Gla-300 (36 vs. 46% with Gla-100; relative risk 0.79 [95% CI 0.67-0.93]; P < 0.005); nocturnal hypoglycemia incidence and event rates were also lower with Gla-300 in the first 8 weeks of treatment. No between-treatment differences in tolerability or safety were identified. CONCLUSIONSGla-300 controls HbA 1c as well as Gla-100 for people with type 2 diabetes treated with basal and mealtime insulin but with consistently less risk of nocturnal hypoglycemia.

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Section: Discussionmentioning

confidence: 67%

New Insulin Glargine 300 Units/mL Versus Glargine 100 Units/mL in People With Type 2 Diabetes Using Basal and Mealtime Insulin: Glucose Control and Hypoglycemia in a 6-Month Randomized Controlled Trial (EDITION 1)

et al. 2014

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“…A -Glyhuman insulin (metabolite M1) is measured separately (16), suggesting that responses to dose adjustments with Gla-300 can be well assessed within a week of treatment initiation, while allowing fast dose adaptations required for acute disease or unplanned physical activities. In contrast, longer terminal half-lives of 25 or 45-76 h, as observed for insulin degludec and LY2605541, respectively, may pose an issue for dose adjustment (20,21).…”

Section: Discussionmentioning

confidence: 99%

New Insulin Glargine 300 Units·mL−1 Provides a More Even Activity Profile and Prolonged Glycemic Control at Steady State Compared With Insulin Glargine 100 Units·mL−1

et al. 2014

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OBJECTIVETo characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a new insulin glargine comprising 300 units·mL 21 (Gla-300), compared with insulin glargine 100 units·mL 21 (Gla-100) at steady state in people with type 1 diabetes. RESEARCH DESIGN AND METHODSA randomized, double-blind, crossover study (N = 30) was conducted, applying the euglycemic clamp technique over a period of 36 h. In this multiple-dose to steadystate study, participants received once-daily subcutaneous administrations of either 0.4 (cohort 1) or 0.6 units·kg 21 (cohort 2) Gla-300 for 8 days in one treatment period and 0.4 units·kg 21 Gla-100 for 8 days in the other. Here we focus on the results of a direct comparison between 0.4 units·kg 21 of each treatment. PK and PD assessments performed on the last treatment day included serum insulin measurements using a radioimmunoassay and the automated euglycemic glucose clamp technique over 36 h. RESULTSAt steady state, insulin concentration (INS) and glucose infusion rate (GIR) profiles of Gla-300 were more constant and more evenly distributed over 24 h compared with those of Gla-100 and lasted longer, as supported by the later time (∼3 h) to 50% of the area under the serum INS and GIR time curves from time zero to 36 h post dosing. Tight blood glucose control (£105 mg·dL 21 ) was maintained for approximately 5 h longer (median of 30 h) with Gla-300 compared with Gla-100. CONCLUSIONSGla-300 provides more even steady-state PK and PD profiles and a longer duration of action than Gla-100, extending blood glucose control well beyond 24 h.Although insulin analog-based products do not exactly replicate dynamic natural portal insulin release, their insulin concentration (INS) profiles closely mimic those of interprandial endogenous insulin levels. However, meeting glycemic goals with oncedaily injections of these agents, while minimizing the frequency of hypoglycemia and

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“…Gla-300 is soluble at acidic pH, and after injection into the subcutaneous tissue microprecipitates form a more compact soluble depot with smaller surface area in comparison with Gla-100, from which active monomers are steadily released. 12 In contrast, IDeg form multi-hexamers after administration in the subcutaneous tissue resulting in the formation of a soluble depot from which active monomers are steadily released. 13 The long half-life of these insulins translates into extended duration of action and therefore allows once-daily administration.…”

Section: Pharmacokinetics and Pharmacodynamics Of Analogue Insulinsmentioning

confidence: 99%

A practical guide to the interpretation of PK/PD profiles of longer-acting analogue insulins. Part one: The principles of glucose clamp studies

Greeff

Tonder

Naidu

et al. 2018

Journal of Endocrinology, Metabolism and Diabetes of South Afri

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Glucose clamp studies are used to determine pharmacokinetics (PK) and pharmacodynamics (PD) of analogue insulins. With the development of longer-acting basal analogue insulins, including glargine 300 (Gla-300) and insulin degludec (IDeg), results from numerous glucose clamp studies are readily available. However, interpreting PK/PD profiles in a scientifically sound manner can be a challenging feat. This is the first in a series of publications that will suggest practical tips for interpreting and comparing results from glucose clamp studies. Variations in the glucose clamp methodology, duration of clamp studies and glucose clamp targets influence the study design and results significantly. Selection of study populations, including healthy patients or patients with Type 1 or 2 diabetes mellitus, has important implications. The dose of study insulin should reflect that of the general treatment population, and ideally steady-state conditions should be used. During the study the plasma insulin concentration and glucose infusion rate describe the pharmacokinetics and pharmacodynamics of the study insulin. With these practical tips in mind, results of glucose clamp studies can be interpreted in a scientifically correct manner. The next article in this series will discuss the interpretation of PK/PD profiles using two newly developed longer-acting basal analogue insulins: Gla-300 and IDeg.

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Investigational new insulin glargine 300 U/ml has the same metabolism as insulin glargine 100 U/ml

Cited by 100 publications

References 11 publications

New Insulin Glargine 300 Units/mL Versus Glargine 100 Units/mL in People With Type 2 Diabetes Using Basal and Mealtime Insulin: Glucose Control and Hypoglycemia in a 6-Month Randomized Controlled Trial (EDITION 1)

New Insulin Glargine 300 Units/mL Versus Glargine 100 Units/mL in People With Type 2 Diabetes Using Basal and Mealtime Insulin: Glucose Control and Hypoglycemia in a 6-Month Randomized Controlled Trial (EDITION 1)

New Insulin Glargine 300 Units·mL−1 Provides a More Even Activity Profile and Prolonged Glycemic Control at Steady State Compared With Insulin Glargine 100 Units·mL−1

A practical guide to the interpretation of PK/PD profiles of longer-acting analogue insulins. Part one: The principles of glucose clamp studies

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