Insulin aspart (HEC)

This trial evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of oral insulin Tregopil (Part 1; results discussed in this paper) and the post‐prandial glucose control with different meal types in comparison with insulin aspart (Part 2) in patients with type 1 diabetes mellitus (T1DM).

This Phase 1, open‐label, multiple ascending dose (30/45/60 mg/60 + 30 mg rescue insulin Tregopil) trial enrolled 37 patients with T1DM (3 female [8.1%], 34 male [91.9%]; median age: 39.5 years). Following screening, patients entered a run‐in phase to optimize their basal‐bolus (insulin glargine and insulin aspart) insulin therapy, and insulin Tregopil was administered orally 10 min before the three major meals of the day in all cohorts during this period. Safety assessments included adverse events and hypo−/hyperglycaemic episodes, vital signs, electrocardiograms, laboratory safety parameters and physical examination. PK and PD were the secondary objectives.

The overall safety profile of insulin Tregopil indicated no safety concerns except a PD effect (hypoglycaemia). The incidence of hypoglycaemia did not increase with increasing doses of insulin Tregopil, and none of the episodes were severe. In general, the variability of the PK/PD parameters was high. Insulin Tregopil demonstrated a rapid onset of action, with peak blood concentrations reached within 15–20 min post‐dosing. Subsequently, insulin Tregopil exerted a PD effect for up to 105 min.

Fixed‐dose insulin Tregopil reduced the requirement for insulin aspart supplementation, although it was not a viable stand‐alone option for the daily management of T1DM. Insulin Tregopil could be explored with a flexible dosing approach and be titrated based on individual needs.

The trial is registered at Clinicaltrials.gov (CT.gov identifier: NCT04141423). The ethical approval number for the protocol is 2019146.

To evaluate the efficacy and safety of faster‐acting insulin aspart (faster aspart) compared with insulin aspart in adults with type 1 diabetes (T1D) using a non‐automated insulin pump and continuous glucose monitoring (CGM).

This double‐blinded crossover study randomly assigned participants to start with either faster aspart or insulin aspart for 16 weeks, followed by a 3‐week washout period, then switching to the alternate therapy for another 16 weeks. Insulin pump settings were adjusted every 3 weeks. The primary outcome was time in range (TIR: 3.9–10.0 mmol/L). Secondary outcomes included other CGM metrics and HbA1c.

Forty adults (20 males) with a median age of 54 years, T1D duration of 27 years, and HbA1c of 59 mmol/mol (7.5%) were included. At the study end, TIR was (mean ± SD) 60.6 ± 12.1% for insulin aspart and 62.5 ± 12.3% for faster aspart, p = 0.24 (primary endpoint). The baseline‐adjusted estimated treatment difference (ETD) for TIR was 6.0% (95%CI: 2.2;9.9), p = 0.002; time above range (>10.0 mmol/L) was −5.7% (−9.8; −1.6), p = 0.007; and time below range (<3.9 mmol/L) was −0.4% (−1.1;0.4), p = 0.30—all in favour of faster aspart. Faster aspart significantly improved the coefficient of variation (34.0 ± 3.7% vs. 35.9 ± 4.9%, p = 0.02) and the HbA1c levels (ETD −1.9 (−3.7; −0.2) mmol/mol or − 0.18% (−0.34;‐0.02), p = 0.03). No significant differences were observed in severe adverse events, including severe hypoglycaemia and diabetic ketoacidosis. Faster aspart had more injection site reactions than insulin aspart (p = 0.03).

Faster aspart improved baseline‐adjusted TIR, TAR, CV and HbA1c after 16 weeks with frequent insulin pump adjustments but had a higher incidence of injection site reactions.