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Continuous Glucose Monitoring Sensor Glucose Levels and Insulin Pump Infusion Set Wear-Time During Treatment with Fast-Acting Insulin Aspart: A Post Hoc Analysis of Onset 5.

ABSTRACT: Background: In the onset 5 trial, fast-acting insulin aspart (faster aspart) was noninferior to insulin aspart (IAsp) for change from baseline glycated hemoglobin at 16 weeks, when used in continuous subcutaneous insulin infusion by participants with type 1 diabetes. The aim of this post hoc analysis was to investigate whether infusion set wear-time was associated with changes in sensor glucose, measured using continuous glucose monitoring (CGM). Materials and Methods: This was a post hoc analysis of onset 5 data. Mean infusion set wear-time and duration of CGM-wearing period were assessed. Mean CGM sensor glucose 24 h before and 24 h after were used to calculate the before-after difference (CGM sensor glucose drift). Results: Mean infusion set wear-time was 2.9 and 3.0 days in the faster aspart and IAsp arms, respectively. At 16 weeks, the average duration of the CGM wearing period was 13.7 and 13.8 days, respectively. Mean CGM sensor glucose before versus after an infusion set change, at week 16, was 10.14 versus 9.39 mmol/L with faster aspart and 9.48 versus 9.47 mmol/L with IAsp. The estimated treatment difference in CGM sensor glucose drift at 16 weeks for faster aspart versus IAsp was +0.72 mmol/L (95% confidence interval: 0.48-0.96, P < 0.001). Conclusions: Mean infusion set wear-time and duration of CGM-wearing period were similar for faster aspart and IAsp. A significantly greater upward drift in CGM sensor glucose values measured during an infusion set wearing period was observed with faster aspart versus IAsp. Clinical trial registration: NCT02825251.

SUBMITTER: Gorst-Rasmussen A

PROVIDER: S-EPMC8783624 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Pharmacological properties of faster-acting insulin aspart vs insulin aspart in patients with type 1 diabetes receiving continuous subcutaneous insulin infusion: A randomized, double-blind, crossover trial.

Project description:AIM:To evaluate the pharmacological characteristics of faster-acting insulin aspart (faster aspart) compared with insulin aspart (IAsp) during continuous subcutaneous insulin infusion (CSII). METHODS:In this randomized, double-blind, crossover trial, 48 men and women aged 18 to 64 years with type 1 diabetes mellitus (T1DM) received faster aspart and IAsp as a 0.15 U/kg bolus dose via CSII, on top of a basal rate (0.02 U/kg/h), in a glucose clamp setting (target 5.5 mmol/L). RESULTS:After a CSII bolus dose, the pharmacokinetic/pharmacodynamic profiles for faster aspart were left-shifted compared with those for IAsp. For faster aspart vs IAsp, the early glucose-lowering effect (area under the curve for glucose infusion rate [GIR]0-30min ) was approximately 2-fold higher (least squares means 24.9 vs 11.4 mg/kg; estimated ratio faster aspart/IAsp 2.18, 95% confidence interval [CI] [1.33; 5.04]; P = .002), onset of glucose-lowering effect (time to early 50% of maximum GIR) occurred 11.1 minutes earlier (41.1 vs 52.3 minutes; 95% CI faster aspart - IAsp [-15.4; -6.9]; P<.001), and offset of glucose-lowering effect (time to late 50% of maximum GIR) occurred 24.0 minutes earlier (214.7 vs 238.7 minutes; 95% CI [-38.9; -9.1]; P=.002). Likewise, significantly greater early exposure and significantly earlier onset and offset of exposure were observed for faster aspart vs IAsp. Faster aspart and IAsp were both well tolerated. CONCLUSIONS:In patients with T1DM using CSII, faster aspart better mimics the endogenous prandial insulin secretion and action than does IAsp. Faster aspart therefore has the potential to provide clinical benefits over current rapid-acting insulins in the insulin pump setting.

| S-EPMC5299522 | biostudies-literature

Improved Postprandial Glycemic Control with Faster-Acting Insulin Aspart in Patients with Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion.

Project description:Faster aspart is insulin aspart (IAsp) in a new formulation, which in continuous subcutaneous insulin infusion (CSII) in subjects with type 1 diabetes has shown a faster onset and offset of glucose-lowering effect than IAsp.This double-blind, randomized, crossover active-controlled trial compared 2-h postprandial plasma glucose (PPG) response, following 2 weeks of CSII with faster aspart or IAsp. Primary endpoint: mean change in PPG 2?h after a standardized meal test (?PGav,0-2h). Subjects (n?=?43) had masked continuous glucose monitoring (CGM) throughout.Faster aspart provided a statistically significantly greater glucose-lowering effect following the meal versus IAsp: ?PGav,0-2h: 3.03?mmol/L versus 4.02?mmol/L (54.68?mg/dL vs. 72.52?mg/dL); estimated treatment difference (ETD) [95% CI]: -0.99?mmol/L [-1.95; -0.03] (-17.84?mg/dL [-35.21; -0.46]; P?=?0.044). One hour postmeal, PG levels were -1.64?mmol/L (-29.47?mg/dL) lower with faster aspart versus IAsp (P?=?0.006). Interstitial glucose (IG) profiles supported these findings; the largest differences were observed at breakfast: 9.08 versus 9.56?mmol/L (163.57 vs. 172.19?mg/dL; ETD [95% CI]: -0.48?mmol/L [-0.97; 0.01]; -8.62?mg/dL [-17.49; 0.24]; P?=?0.057). Duration of low IG levels (?3.9?mmol/L [70?mg/dL] per 24?h) was statistically significantly shorter for faster aspart versus IAsp (2.03?h vs. 2.45?h; ETD [95% CI]: -0.42 [-0.72; -0.11]; P?=?0.008). No unexpected safety findings were observed.CSII delivery of faster aspart had a greater glucose-lowering effect than IAsp after a meal test. CGM results recorded throughout all meals supported this finding, with less time spent with low IG levels.

| S-EPMC5248540 | biostudies-literature

Greater early postprandial suppression of endogenous glucose production and higher initial glucose disappearance is achieved with fast-acting insulin aspart compared with insulin aspart.

Project description:AIM:To investigate the mechanisms behind the lower postprandial glucose (PPG) concentrations achieved with fast-acting insulin aspart (faster aspart) than with insulin aspart (IAsp). MATERIALS AND METHODS:In a randomized, double-blind, crossover trial, 41 people with type 1 diabetes received identical subcutaneous single faster aspart and IAsp doses (individualized for each participant), together with a standardized mixed meal (including 75 g carbohydrate labelled with [1-13 C] glucose). PPG turnover was determined by the triple-tracer meal method using continuous, variable [6-3 H] glucose and [6,6-2 H2 ] glucose infusion. RESULTS:Insulin exposure within the first hour was 32% greater with faster aspart than with IAsp (treatment ratio faster aspart/IAsp 1.32 [95% confidence interval {CI} 1.18;1.48]; P < .001), leading to a 0.59-mmol/L non-significantly smaller PPG increment at 1 hour (?PG1h ; treatment difference faster aspart-IAsp -0.59 mmol/L [95% CI -1.19; 0.01]; P = .055). The trend towards reduced ?PG1h with faster aspart was attributable to 12% greater suppression of endogenous glucose production (EGP; treatment ratio 1.12 [95% CI 1.01; 1.25]; P = .040) and 23% higher glucose disappearance (1.23 [95% CI 1.05; 1.45]; P = .012) with faster aspart than with IAsp during the first hour. Suppression of free fatty acid levels during the first hour was 36% greater for faster aspart than for IAsp (1.36 [95% CI 1.01;1.88]; P = .042). CONCLUSIONS:The trend towards improved PPG control with faster aspart vs IAsp in this study was attributable to both greater early suppression of EGP and stimulation of glucose disappearance.

| S-EPMC6033168 | biostudies-literature

Investigation of Pump Compatibility of Fast-Acting Insulin Aspart in Subjects With Type 1 Diabetes.

Project description:BACKGROUND:Ultra-fast-acting insulins, such as fast-acting insulin aspart (faster aspart), have pharmacokinetic properties that may be advantageous for patients using continuous subcutaneous insulin infusion (CSII), provided that they are compatible with and safe to use in CSII. METHODS:Randomized, double-blind, parallel-group, actively controlled trial evaluating compatibility, efficacy, and safety of faster aspart in adults with type 1 diabetes using their own MiniMed Paradigm pump with Quick-Set or Silhouette infusion sets. Following run-in, subjects were randomized (2:1) to faster aspart (n = 25) or insulin aspart (n = 12) for 6 weeks. Primary endpoint was the number of microscopically confirmed episodes of infusion-set occlusions. RESULTS:No microscopically confirmed episodes of infusion-set occlusions were observed in either arm. Seven possible infusion-set occlusions were reported by five subjects (all faster aspart); none were prompted by a plug observed by the subject (prompted by unexplained hyperglycemia [n = 6] or leakage [n = 1]) and none were confirmed. Macroscopic and microscopic evaluation showed no color change or particle/crystal formation in the infusion sets. Premature infusion-set changes were reported in 44% and 16.7% of subjects in the faster aspart and insulin aspart groups, respectively. A nonsignificant trend toward better efficacy was observed with faster aspart (estimated treatment difference [ETD] [95% CI] in HbA1c change: -0.14% [-0.40, 0.11]). No new safety issues were found in either treatment group. CONCLUSIONS:Over 6 weeks of treatment, no microscopically confirmed infusion-set occlusions were observed for faster aspart or insulin aspart, indicating similar compatibility with CSII use.

| S-EPMC5761985 | biostudies-literature

A randomized, multicentre trial evaluating the efficacy and safety of fast-acting insulin aspart in continuous subcutaneous insulin infusion in adults with type 1 diabetes (onset 5).

Project description:AimTo evaluate the efficacy and safety of fast-acting insulin aspart (faster aspart) vs insulin aspart (IAsp) used in continuous subcutaneous insulin infusion (CSII) in participants with type 1 diabetes (T1D).Materials and methodsThis was a double-blind, treat-to-target, randomized, 16-week trial investigating CSII treatment with faster aspart (n = 236) or IAsp (n = 236). All available information, regardless of treatment discontinuation, was used for the evaluation of effect.ResultsFaster aspart was non-inferior to IAsp regarding the change from baseline in glycated haemoglobin (HbA1c; primary endpoint). The mean HbA1c changed from 58.4 mmol/mol (7.5%) at baseline to 57.8 mmol/mol (7.4%) with faster aspart and to 56.8 mmol/mol (7.4%) with IAsp after 16 weeks' treatment, with an estimated treatment difference (ETD) of 1.0 mmol/mol (95% confidence interval [CI] 0.14; 1.87) or 0.09% (95% CI 0.01; 0.17; P < 0.001) for non-inferiority (0.4% margin; P < 0.02 for statistical significance in favour of IAsp). Faster aspart was superior to IAsp in change from baseline in 1-hour postprandial glucose (PPG) increment after a meal test (ETD -0.91 mmol/L [95% CI -1.43; -0.39] or -16.4 mg/dL [95% CI -25.7; -7.0]; P = 0.001), with statistically significant reductions also at 30 minutes and 2 hours. The improvement in PPG was reflected in the change from baseline in 1-hour interstitial glucose increment after all meals (ETD -0.21 mmol/L [95% CI -0.31; -0.11] or -3.77 mg/dL [95% CI -5.53; -2.01]). There was no statistically significant difference in the overall rate of severe or blood glucose-confirmed hypoglycaemia (estimated rate ratio 1.00 [95% CI 0.85; 1.16]). A numerical imbalance in severe hypoglycaemic episodes between faster aspart and IAsp was seen in the treatment (21 vs 7) and 4-week run-in periods (4 vs 0).ConclusionsFaster aspart provides an effective and safe option for CSII treatment in T1D.

| S-EPMC6590130 | biostudies-literature

Fast-acting insulin aspart in people with type 2 diabetes: Earlier onset and greater initial exposure and glucose-lowering effect compared with insulin aspart.

Project description:AIMS:To investigate the pharmacokinetic/pharmacodynamic properties of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp) in people with type 2 diabetes (T2D). MATERIALS AND METHODS:In a randomized, double-blind, crossover design, 61 people with T2D usually treated with insulin?±?oral antidiabetic drug(s) received single-dose faster aspart and IAsp (0.3 U/kg) on separate visits. Blood samples for pharmacokinetic assessment were collected frequently until 12?hours post-dose. Glucose-lowering effect was determined in a euglycaemic clamp lasting up to 12?hours post-dose (target 5.0 mmol/L). RESULTS:The serum IAsp pharmacokinetic profile and glucose-lowering effect profile were shifted to the left for faster aspart versus IAsp. Least squares mean (± SE) onset of appearance was 3.3?±?0.3 minutes for faster aspart, which was 1.2 minutes earlier than for IAsp (95% confidence interval [CI] -1.8;-0.5; P?=?.001). Onset of action for faster aspart was 8.9 minutes earlier (95% CI -12.1;-5.7; P?<?.001) than for IAsp. During the first 30?minutes after dosing, 89% larger IAsp exposure (ratio faster aspart/IAsp 1.89 [95% CI 1.56;2.28]; P?<?.001) and 147% greater glucose-lowering effect (2.47 [95% CI 1.58;6.22]; P?<?.001) were observed for faster aspart compared with IAsp. Offset of exposure (time to 50% of maximum IAsp concentration in the late part of the pharmacokinetic profile) occurred earlier for faster aspart (difference faster aspart - IAsp -36.4 minutes [95% CI -55.3;-17.6]; P?<?.001). The treatment difference of faster aspart - IAsp in offset of glucose-lowering effect (time to 50% of maximum glucose infusion rate in the late part of the glucose infusion rate profile) was -14.4 minutes (95% CI -34.4;5.5; P?=?.152). CONCLUSIONS:In people with T2D, faster aspart was associated with earlier onset and greater initial exposure and glucose-lowering effect compared with IAsp, as previously shown in people with type 1 diabetes.

| S-EPMC6771872 | biostudies-literature

Improved postprandial glucose control with ultra rapid lispro versus lispro with continuous subcutaneous insulin infusion in type 1 diabetes: PRONTO-Pump-2.

Project description:AimTo evaluate the efficacy and safety of ultra rapid lispro (URLi) versus lispro (Humalog® ) in people with type 1 diabetes on continuous subcutaneous insulin infusion (CSII).Materials and methodsThis was a phase 3, 16-week, treat-to-target study in patients randomized to double-blind URLi (N = 215) or lispro (N = 217). The primary endpoint was change from baseline HbA1c (non-inferiority margin 4.4 mmol/mol [0.4%]), with multiplicity-adjusted objectives for postprandial glucose (PPG) levels during a meal test, and time spent in the target range 70-180 mg/dL (TIR).ResultsURLi was non-inferior to lispro for change in HbA1c, with a least-squares mean (LSM) difference of 0.3 mmol/mol (95% confidence interval [CI] -0.6, 1.2) or 0.02% (95% CI -0.06, 0.11). URLi was superior to lispro in controlling 1- and 2-h PPG levels after the meal test: LSM difference -1.34 mmol/L (95% CI -2.00, -0.68) or -24.1 mg/dL (95% CI -36.0, -12.2) at 1 h and -1.54 mmol/L (95% CI -2.37, -0.72) or -27.8 mg/dL (95% CI -42.6, -13.0) at 2 h; both p < .001. TIR and time in hyperglycaemia were similar between groups but URLi resulted in significantly less time in hypoglycaemia (<3.0 mmol/L [54 mg/dL]) over the daytime, night-time and 24-h period: LSM difference -0.41%, -0.97% and -0.52%, respectively, all p < .05. The incidence of treatment-emergent adverse events was higher with URLi (60.5% vs. 44.7%), driven by infusion-site reaction and infusion-site pain, which was mostly mild or moderate. Rates of severe hypoglycaemia and diabetic ketoacidosis were similar between groups.ConclusionsURLi was efficacious, providing superior PPG control and less time in hypoglycaemia but with more frequent infusion-site reactions compared with lispro when administered by CSII.

| S-EPMC8251988 | biostudies-literature

Fast-acting insulin aspart in Japanese patients with type 1 diabetes: Faster onset, higher early exposure and greater early glucose-lowering effect relative to insulin aspart.

Project description:Fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with two added excipients (niacinamide and L-arginine) in order to obtain accelerated absorption after subcutaneous dosing. The present study compared the pharmacokinetic/pharmacodynamic characteristics of faster aspart vs IAsp in Japanese patients with type 1 diabetes.In a randomized, double-blind, cross-over design, 43 participants were given faster aspart and IAsp (0.2 U/kg single dose) at two separate dosing visits. Frequent pharmacokinetic blood sampling was carried out, and pharmacodynamics were assessed using an automated euglycemic clamp lasting for a maximum of 12 h after dosing (target 5.5 mmol/L).Faster aspart showed onset of appearance approximately twice-as-fast vs IAsp (least squares means: 3.0 vs 7.1 min; estimated treatment difference -4.1 min, 95% confidence interval [CI]: -5.0, -3.2; P < 0.001) and onset of action occurring approximately 5 min earlier (20.2 vs 25.5 min; estimated treatment difference -5.3 min, 95% CI: -8.4, -2.2; P = 0.001). Within the first 30 min post-dose, both exposure (area under the curve [AUC]IAsp,0-30 min ) and glucose-lowering effect (AUCGIR,0-30 min ) were approximately twofold greater for faster aspart vs IAsp (P < 0.001 and P = 0.002, respectively). Bioavailability of faster aspart was similar to IAsp (AUCIAsp,0-t ; estimated treatment ratio 0.99, 90% CI: 0.96-1.02), whereas the total glucose-lowering effect (AUCGIR,0-t ) was slightly lower for faster aspart vs IAsp (estimated treatment ratio 0.93, 95% CI: 0.87-0.99, P = 0.020).Faster aspart showed faster onset, higher early exposure and a greater early glucose-lowering effect relative to IAsp in Japanese patients with type 1 diabetes, in accordance with previous findings in Caucasian type 1 diabetes patients.

| S-EPMC5835461 | biostudies-literature

Mealtime fast-acting insulin aspart versus insulin aspart for controlling postprandial hyperglycaemia in people with insulin-resistant Type 2 diabetes.

Project description:AimThis post hoc analysis explored whether mealtime fast-acting insulin aspart treatment provided an advantage in postprandial plasma glucose (PPG) control vs. insulin aspart in people with Type 2 diabetes receiving high doses of bolus insulin.MethodsA post hoc, post-randomization, subgroup analysis of a 26-week, randomized, double-blind, treat-to-target trial (onset 2) that compared mealtime fast-acting insulin aspart vs. mealtime insulin aspart, both in a basal-bolus regimen, in people with Type 2 diabetes uncontrolled on basal insulin therapy and metformin. At the end of trial, the impact of fast-acting insulin aspart and insulin aspart on PPG control was assessed with a standard liquid meal test and participants were grouped into three post-randomization subgroups: meal test bolus insulin dose ≤ 10 units per dose (n = 171), > 10-20 units per dose (n = 289) and > 20 units per dose (n = 146).ResultsA statistically significant treatment difference in favour of fast-acting insulin aspart vs. insulin aspart was observed for the change in PPG increment at all post-meal time points (from 1 to 4 h) for those in the > 20 units bolus insulin subgroup. There was no difference in the magnitude of change from baseline in HbA1c level between fast-acting insulin aspart and insulin aspart in any of the bolus insulin dose subgroups (data herein).ConclusionFast-acting insulin aspart may hold promise as a more effective treatment compared with insulin aspart for controlling PPG in people with insulin-resistant Type 2 diabetes.

| S-EPMC6588019 | biostudies-literature

Consequences of delayed pump infusion line change in patients with type 1 diabetes mellitus treated with continuous subcutaneous insulin infusion.

Project description:ObjectiveTo systematically investigate the effect of lack of adherence to the recommended change in insulin pump infusion line use beyond 48 h and determine whether the type of insulin made a difference.Research design and methodsThis was a double-blind, randomized, crossover trial with 20 patients with diabetes mellitus I using insulins aspart and lispro without a line change for up to 100 h. Using retrospective continuous glucose monitoring, we analyzed the average glucose over the day. Changes in serum 1,5-anhydroglucitol, carboxymethyllysine, and free 15-F(2t) isoprostane were also studied.ResultsFrom Day 2 to Day 5 of the pump line use, the daily average glucose level increased from 122.7 to 163.9 mg/dl (P<.05), fasting glucose from 120.3 to 154.5 mg/dl (P<.05), postprandial glucose from 114.6 to 172.1 mg/dl (P<.05), and the daily maximum glucose from 207.7 to 242.8 dl (P<.05 for the trend). Time period that the glucose was >180 mg/dl increased from 14.5% to 38.3% (P<.05). Loss of control occurred despite increase in total daily insulin dose from 48.5+/-11.8 to 55.3+/-17.9 U (P=.05). There was no difference in loss of control between insulin types, and biomarkers measured did not change significantly.ConclusionsThe insulin pump infusion should be changed every 48 h in patients using continuous subcutaneous insulin infusion (CSII), to avoid loss of glycemic control. In the short-term, this loss of glycemic control has no impact on oxidative stress and glycation.

| S-EPMC2854665 | biostudies-literature

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