Dataset Information

Efficacy and Safety of Fast-Acting Insulin Aspart in People with Type 1 Diabetes Using Carbohydrate Counting: A Post Hoc Analysis of Two Randomised Controlled Trials.

ABSTRACT:

Introduction

Insulin dosing based on carbohydrate counting is the gold standard for improving glycaemic control in type 1 diabetes (T1D). This post hoc analysis aimed to explore the efficacy and safety of fast-acting insulin aspart (faster aspart) according to bolus dose adjustment method in people with T1D.

Methods

Post hoc analysis of two 26-week, treat-to-target, randomised trials investigating treatment with double-blind mealtime faster aspart, insulin aspart (IAsp), or open-label post-meal faster aspart (onset 1, n = 1143; onset 8, n = 1025). Participants with previous experience continued carbohydrate counting (onset 1, n = 669 [58.5%]; onset 8, n = 428 [41.8%]), while remaining participants used a bolus algorithm.

Results

In onset 1, HbA1c reduction was statistically significantly in favour of mealtime faster aspart versus IAsp with carbohydrate counting (estimated treatment difference [ETD 95% CI] - 0.19% [- 0.30; - 0.09]; - 2.08 mmol/mol [- 3.23; - 0.93]). In onset 8, there was no statistically significant difference in HbA1c reduction with either dose adjustment method, although a trend towards improved HbA1c was observed for mealtime faster aspart with carbohydrate counting (ETD - 0.14% [- 0.28; 0.003]; - 1.53 mmol/mol [- 3.10; 0.04]). In both trials, bolus insulin doses and overall rates of severe or blood glucose-confirmed hypoglycaemia were similar between treatments across dose adjustment methods.

Conclusion

For people with T1D using carbohydrate counting, mealtime faster aspart may offer improved glycaemic control versus IAsp, with similar insulin dose and weight gain and no increased risk of hypoglycaemia.

Trial registration

ClinicalTrials.gov: NCT01831765 (onset 1) and NCT02500706 (onset 8).

Funding

Novo Nordisk.

SUBMITTER: Rose L

PROVIDER: S-EPMC6531584 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThis study investigated glycaemic control in individuals with type 1 (T1D) or type 2 diabetes (T2D) 6 months after initiating fast-acting insulin aspart (faster aspart) in a real-world setting.MethodsThis was a single-arm, observational study using extracted patient data from the IBM® Explorys® database (USA) for individuals with T1D or T2D initiating faster aspart (at least one prescription of faster aspart) in the study period 1 January 2018 to 27 October 2020. Clinical characteristics, including age, body mass index, and baseline HbA1c, were extracted, as well as recorded events of hypoglycaemia. The primary endpoint was the change in HbA1c from baseline to 6 months.ResultsA total of 787 individuals were included; 36.6% of these individuals had T1D and 63.4% had T2D (of whom 46.9% were new users of rapid-acting insulin when initiating faster aspart [T2D new users] and 53.1% were switching from another rapid-acting insulin to faster aspart [T2D switchers]). For individuals with T1D, T2D new users, or T2D switchers, estimated mean change in HbA1c from baseline to 6 months was - 0.20% (95% CI - 0.53, 0.14; p = 0.252), - 1.00% (95% CI - 1.34, - 0.67; p < 0.0001), and - 0.70% (95% CI - 1.06, - 0.35; p = 0.0001), respectively. In the baseline HbA1c > 8.5% subgroup, there was a significant estimated decrease in HbA1c from baseline to 6 months in individuals with T1D (- 1.2% [95% CI - 1.80, - 0.60]; p = 0.0001) or T2D (- 0.6% [95% CI - 0.92, - 0.35]; p < 0.0001). Event rates of hypoglycaemia after 12 months were 0.68, 0.38, and 0.59 events/year for individuals with T1D, T2D new users, and T2D switchers, respectively.ConclusionUS IBM® Explorys® data demonstrated a clinically relevant reduction in HbA1c 6 months after initiating faster aspart treatment for individuals with T2D, but not T1D overall, although patients with baseline HbA1c > 8.5% had significant HbA1c reductions regardless of diabetes type.

Project description:INTRODUCTION:The aim of this study was to investigate the association between baseline characteristics [HbA1c and body mass index (BMI)] and the effect of mealtime fast-acting insulin aspart (faster aspart) relative to insulin aspart (IAsp) or basal-only insulin therapy on several efficacy and safety outcomes in people with diabetes. METHODS:Post hoc analysis of three randomised phase 3a trials in people with type 1 diabetes (T1D; onset 1) and type 2 diabetes (T2D; onset 2 and 3). Participants (N = 1686) were stratified according to baseline BMI (< 25 kg/m2, 25-< 30 kg/m2, ≥ 30 kg/m2) or HbA1c (≤ 58 mmol/mol, > 58-< 64 mmol/mol, ≥ 64 mmol/mol; ≤ 7.5%, > 7.5-< 8.0%, ≥ 8.0%). RESULTS:In participants with T2D, the estimated treatment difference for change in HbA1c was similar for all BMI and HbA1c subgroups. No major differences between treatments were observed in risk of overall hypoglycaemia or insulin dose across subgroups. In participants with T1D, change in HbA1c was similar across BMI and HbA1c subgroups, and no major differences between treatments were observed for severe or blood glucose-confirmed hypoglycaemia across subgroups. Total daily insulin dose (U/kg) was similar across all baseline HbA1c groups and the BMI < 25 kg/m2 and 25-30 kg/m2 groups, but was significantly lower with mealtime faster aspart compared with IAsp in the BMI > 30 kg/m2 subgroup. CONCLUSIONS:In participants with T1D and T2D, treatment differences (for change in HbA1c and overall hypoglycaemia) between mealtime faster aspart and insulin comparators were similar to the corresponding overall analysis across baseline HbA1c and BMI subgroups. The finding of a lower total daily insulin dose in participants with obesity (BMI > 30 kg/m2) and T1D treated with faster aspart, versus those treated with IAsp, may warrant further investigation. TRIAL REGISTRATION:ClinicalTrials.gov NCT01831765 (onset 1); NCT01819129 (onset 2); NCT01850615 (onset 3). FUNDING:Novo Nordisk A/S, Søborg, Denmark.

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