Ultra rapid lispro as good as lispro in reducing HbA1c
Ultra rapid lispro (URLi) was noninferior to lispro in reducing HbA1c levels in adults with type 1 diabetes (T1D), according to the PRONTO-Pump-2* study presented at EASD 2020.
“URLi is a novel, prandial, insulin lispro formulation developed to more closely match physiological insulin secretion ... With multiple daily injections (MDIs), URLi has shown superior post-prandial glucose (PPG control) and noninferior HbA1c reduction compared to lispro,” said Dr Mark Warren from Physicians East Professional Association in Greenville, North Carolina, US.
This phase III, double-blind, parallel, active-controlled trial analysed 432 patients with T1D (mean HbA1c 7.55 percent; mean diabetes duration of 25.6 years). Participants were randomized to receive either URLi (n=215; mean age 48.2 years) or lispro (n=217, mean age 44.7 years) administered via CSII** for 16 weeks. The primary endpoint of the study was the change in HbA1c level at 16 weeks. PPG control was assessed with a standardized meal test at randomization and week 16. [EASD 2020, abstract 58]
URLi was noninferior to lispro in terms of HbA1c reduction from baseline to week 16 (from 7.56 to 7.48 percent for URLi and from 7.54 to 7.46 percent for lispro).
Moreover, based on mixed meal tolerance test, URLi demonstrated superiority to lispro in controlling PPG levels at 1-hour (least squares mean [LSM] difference, -1.34 mmol/L; p<0.001) and 2-hour post-meal (LSM difference, -1.54 mmol/L; p<0.001).
The mean post-meal incremental area under the curve (AUC) was significantly reduced by 46 percent from 0–1 hour (0.29 vs 0.54 mmol h/L; p<0.001) and by 37 percent from 0–2 hour (1.03 vs 1.64 mmol h/L; p<0.001) with URLi compared with lispro.
Among patients with hypoglycaemia (<3.0 mmol/L), URLi users spent significantly less time in hypoglycaemia than lispro users during daytime (14.8 vs 19.2 minutes; p=0.029), nighttime (6.82 vs 10.3 minutes; p=0.007), and the 24-hour period (21.7 vs 29.1 minutes; p=0.006).
URLi users also achieved a significantly lower rate of post-meal hypoglycaemia at 2–4 hours (47.2 percent vs 48.9; p=0.041) and ≤4 hours (47.2 percent vs 48.9 percent; p=0.044). “[Of note,] post-meal hypoglycaemia was lower with URLi despite having lower post-prandial blood sugars,” said Warren.
Patients on lispro also had a significantly lower rate of all documented hypoglycaemia (84.4 percent vs 85.6 percent; p=0.049) than those on lispro, while similar rate of nocturnal hyperglycaemia was observed between the two treatment arms (45.8 percent vs 53.4 percent).
Among patients with blood glucose level of <3.9 mmol/L, a significantly reduced time spent in hypoglycaemia was observed with URLi compared with lispro (46.0 vs 54.4 minutes; p=0.028 [daytime], 16.7 vs 23.5 minutes; p=0.002 [nighttime], and 62.9 vs 77.2 minutes; p=0.006 [24-hour period]).
On the other hand, those with blood glucose level of >10.0 and >13.9 mmol/L, a similar time spent in hyperglycaemia was noted across all time points, Warren noted.
However, treatment-emergent adverse events (AEs), particularly infusion site pain and reaction, occurred more frequently in the URLi arm than the lispro arm (60.5 percent vs 44.7 percent), which were mostly mild or moderate in severity. Also, more patients in the URLi arm discontinued study treatment due to AEs than those in the lispro arm (6.0 percent vs 0.9 percent).
“Compared with lispro, when delivered by CSII in patients with T1D, URLi demonstrated noninferior HbA1c reduction, superior PPG control, less [time in] hypoglycaemia, and an acceptable safety profile,” Warren concluded.
“[Of note,] URLi is currently approved for both MDI and CSII (insulin pump) [therapy] in the EU, Japan, and Brazil, and for MID in the US” said Warren.
*PRONTO-Pump-2: A study comparing LY900014 to insulin lispro (Humalog) in adults with type 1 diabetes using insulin pump therapy
**CSII: Continuous subcutaneous insulin infusion