Adding fast-acting insulin aspart to basal insulin significantly improved glycaemic control in patients with type 2 diabetes: A randomized, 18-week, open-label, phase 3 trial (onset 3)

Abstract

Aim: To confirm glycaemic control superiority of mealtime fast-acting insulin aspart (faster aspart) in a basal-bolus (BB) regimen vs basal-only insulin.

Materials and methods: In this open-label, randomized, 18-week trial (51 sites; 6 countries), adults (n = 236) with inadequately controlled type 2 diabetes (T2D; mean glycosylated haemoglobin [HbA1c] ± SD: 7.9% ± 0.7% [63.1 ± 7.5 mmol/mol]) receiving basal insulin and oral antidiabetic drugs underwent 8-week optimization of prior once-daily basal insulin followed by randomization 1:1 to either a BB regimen with faster aspart (n = 116) or continuation of once-daily basal insulin (n = 120), both with metformin. Primary endpoint was HbA1c change from baseline after 18 weeks of treatment. Secondary endpoints included: postprandial plasma glucose (PPG) change and overall PPG increment (all meals); weight; treatment-emergent adverse events; hypoglycaemic episodes.

Results: HbA1c decreased from 7.9% (63.2 mmol/mol) to 6.8% (50.7 mmol/mol; BB group) and from 7.9% (63.2 mmol/mol) to 7.7% (60.7 mmol/mol; basal-only group); estimated treatment difference [95% confidence interval] -0.94% [-1.17; -0.72]; -10.3 mmol/mol [-12.8; -7.8]; P < .0001. Reductions from baseline in overall mean 2-hour PPG and overall PPG increment for all meals (self-measured plasma glucose profiles) were statistically significant in favour of BB treatment ( P < .0001). Severe/blood glucose confirmed hypoglycaemia rate (12.8 vs 2.0 episodes per patient-years of exposure), total daily insulin (1.2 vs 0.6 U/kg) and weight gain (1.8 vs 0.2 kg) were greater with BB than with basal-only treatment.

Conclusions: In T2D, faster aspart in a BB regimen provided superior glycaemic control as compared with basal-only insulin, but with an increase in the frequency of hypoglycaemia and modest weight gain.

Trial registration: ClinicalTrials.gov NCT01850615.

Keywords: glycaemic control; hypoglycaemia; insulin therapy; phase 3 study; randomized trial; type 2 diabetes.

Figure 1

Participant disposition. A total of 323 participants entered the run‐in period of the trial; the most common reason for failure during the run‐in period was failure to meet randomization criteria (HbA1c 7.0%‐9.0% [53‐75 mmol/mol]) at Visit 9 (Week –1). The pattern of withdrawal was low and comparable between groups, with 94.1% of participants completing the trial. HbA1c, glycosylated haemoglobin

Figure 2

Observed mean HbA1c change from baseline to Week 18 (A), participants who achieved target HbA1c (B) and PPG levels (C) at Week 18. *P < .0001. Error bars: ± standard error of the mean. HbA1c targets: <7.0% (53.0 mmol/mol) and ≤6.5% (47.5 mmol/mol), and <7.0% (53.0 mmol/mol) and ≤6.5% (47.5 mmol/mol) without SH. PPG (based on SMPG) target: 2‐hour PPG ≤ 7.8 mmol/L (140 mg/dL) and 2‐hour PPG ≤7.8 mmol/L (140 mg/dL) without SH. Basal insulin: insulin detemir, insulin glargine U100 or NPH insulin. CI, confidence interval; faster aspart, fast‐acting insulin aspart; HbA1c, glycosylated haemoglobin; NPH, neutral protamine Hagedorn; OR, estimated odds ratio; PPG, postprandial plasma glucose; SH, severe hypoglycaemia during treatment period; SMPG, self‐measured plasma glucose. The conversion factor used for glucose between mmol/L and mg/dL was 0.0555

Figure 3

Eight‐point SMPG profiles at baseline (A) and Week 18 (B). Values are based on the full analysis set and averaged for each time point ± standard error of the mean. Basal insulin: insulin detemir, insulin glargine U100 or NPH insulin. Faster aspart, fast‐acting insulin aspart; NPH, neutral protamine Hagedorn; SMPG, self‐measured plasma glucose. The conversion factor used for glucose between mmol/L and mg/dL was 0.0555