A Comparison of the Steady-State Pharmacokinetic and Pharmacodynamic Profiles of 100 and 200 U/mL Formulations of Ultra-Long-Acting Insulin Degludec

Abstract

IDeg U100 and U200 formulations are bioequivalent and have similar pharmacodynamic profiles at SS, implying that they can be used interchangeably in clinical practice.

Low Within- and Between-Day Variability in Exposure to New Insulin Glargine 300 U/mL

“…In addition, PD response is not perfectly synchronized with changes in observed insulin concentrations [9], as displayed by the subtle difference between ratios of INS-and GIR-AUC fractions in this and previous studies [10,11]. Foremost, the results of this study suggest that a therapeutic dose of Gla-300 confers a low level of fluctuation at a high level of reproducibility in exposure, in steady-state conditions in people with T1DM.…”

“…Although insulin variability can be measured both in terms of exposure (PK) and metabolic effect (PD), only insulin concentrations are a direct measure of variability attributable to the insulin product [3]. The PD response, by contrast, reflects not only the availability of insulin, but largely the within-subject variability in insulin sensitivity and demand, as well as the smoothing algorithm INS-AUC [6][7][8][9][10][11][12] INS-AUC [12][13][14][15][16][17][18] INS-AUC [18][19][20][21][22][23][24] GIR-AUC 0-6 GIR-AUC [6][7][8][9][10][11][12] GIR-AUC [12][13][14][15][16][17][18] GIR-AUC [18][19][20][21][22][23][24] Absolute exposure (μU.h/ml) …”

“…Using a different retarding principle (formation of multi-hexamer complexes upon subcutaneous injection and subsequent binding to plasma albumin), insulin degludec is reported to show a similar even distribution of exposure and activity at steady state in people with T2DM [14] and T1DM [10]. In a study of people with T2DM, Heise et al [11] reported an almost equal distribution (12-h fractions) of insulin degludec activity over 24 h at steady state, irrespective of dose (GIR-AUC 0-12 /GIR-AUC 0-24 of 0.49, 0.53 and 0.50 at 0.4, 0.6 and 0.8 U/kg), at exposure ratios (INS-AUC 0-12 /INS-AUC 0-24 ) of 0.53 for all doses.…”

Insulin U100, 200, 300 or 500?

“…Glucose infusion rates were horizontal but increased proportionately with increasing doses. [12][13][14] There was no clinically relevant difference REVIEW in the handling of insulin degludec by younger people compared with an older group. 15 The duration of action of insulin degludec was reported to be >42 h. 11 …”

Modern basal insulins: an ongoing story or the start of a new era?

“…Ретроспективный анализ исследований инсулина деглудек 200 Ед/мл показал, что он биоэквивалентен форме деглудек 100 Ед/мл и оказывает такое же сахаро-снижающее действие [27]. Согласно исследованиям вы-сокодозной формы инсулина деглудек 200 Ед/мл BEGIN LOW VOLUME, его применение 1 раз в день у пациентов с СД2 способствовало такому же улучшению показате-лей гликемического контроля, как и инсулин гларгин 100 Ед/мл, снижало риск всех и ночных подтвержденных эпизодов гипогликемии на 14% и 36% соответственно (при использовании в дозе ≥60 Ед/день -на 16% и 44%, а в дозе ≥80 Ед/день -на 18% и 64% ниже соответ-ственно) [28].…”