Dataset Information

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

ABSTRACT:

Aim

To 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 methods

This 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).

Results

URLi 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.

Conclusions

URLi 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.

SUBMITTER: Warren M

PROVIDER: S-EPMC8251988 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionTo assess time in range (TIR) (70-180 mg/dL) with postprandial glucose (PPG)-focused titration of ultra rapid lispro (URLi; Lyumjev®) in combination with insulin degludec in people with type 1 diabetes (T1D).MethodsThis phase 2, single-group, open-label, exploratory study was conducted in 31 participants with T1D on multiple daily injection therapy. Participants were treated with insulin degludec and Lispro for an 11-day lead-in and then URLi for a 46-day treatment period consisting of 35-day titration and 11-day endpoint maintenance period. Glucose targets for the titration period were PPG < 140 mg/dL or < 20% increase from premeal, fasting glucose 80-110 mg/dL, and overnight excursion ± 30 mg/dL or less. Participants used the InPen™ bolus calculator and Dexcom G6 continuous glucose monitoring (CGM).ResultsPrimary endpoint mean TIR (70-180 mg/dL) with URLi during the maintenance period was 70.2%. TIR (70-180 mg/dL) and times below/above range were not significantly different with URLi (maintenance) versus lispro (lead-in). HbA1c decreased from 7.1% at screening to 6.8% at endpoint (least squares mean [LSM] change from baseline, - 0.36%; P < 0.001). Fructosamine and 1,5-anhydroglucitol improved (P < 0.001). Mean hourly glucose using CGM was reduced from 8:00 AM to 4:00 PM with URLi. Overall highest PPG excursion across meals was significantly reduced at URLi endpoint compared with lispro lead-in (mean 56.5 vs 72.4 mg/dL; P < 0.001). Insulin-to-carbohydrate ratio (U/X g) was reduced (more insulin given) at breakfast at URLi endpoint vs lead-in (LSM 9.0 vs 9.7 g; P = 0.002) and numerically decreased at other meals. Total daily insulin dose (TDD) was higher at URLi endpoint compared with lispro lead-in (mean 50.2 vs 47.0 U; P = 0.046) with similar prandial/TDD ratio (mean 52.1% vs 51.2%). There were no severe hypoglycemia events during the study.ConclusionsURLi in a basal-bolus regimen focusing on PPG targets demonstrated improved overall glycemic control and reduced PPG excursions without increased hypoglycemia in participants with T1D.Trial registrationClinicalTrial.gov, NCT04585776.