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Clinical Trial
. 2020 Dec;43(12):2991-2998.
doi: 10.2337/dc19-2550. Epub 2020 Jul 2.

Randomized Double-Blind Clinical Trial Comparing Ultra Rapid Lispro With Lispro in a Basal-Bolus Regimen in Patients With Type 2 Diabetes: PRONTO-T2D

Thomas Blevins  1 , Qianyi Zhang  2 , Juan P Frias  3 , Hideaki Jinnouchi  4 , Annette M Chang; PRONTO-T2D Investigators
Affiliations
Clinical Trial

Randomized Double-Blind Clinical Trial Comparing Ultra Rapid Lispro With Lispro in a Basal-Bolus Regimen in Patients With Type 2 Diabetes: PRONTO-T2D

Thomas Blevins et al. Diabetes Care. 2020 Dec.

Abstract

Objective: To evaluate the efficacy and safety of ultra rapid lispro (URLi) versus lispro in patients with type 2 diabetes on a basal-bolus insulin regimen.

Research design and methods: This was a phase 3, treat-to-target, double-blind 26-week study. After an 8-week lead-in to optimize basal insulin glargine or degludec in combination with prandial lispro treatment, patients were randomized to blinded URLi (n = 336) or lispro (n = 337) injected 0-2 min prior to meals. Patients could continue metformin and/or a sodium-glucose cotransporter 2 inhibitor. The primary end point was change in HbA1c from baseline to 26 weeks (noninferiority margin 0.4%), with multiplicity-adjusted objectives for postprandial glucose (PPG) excursions during a standardized meal test.

Results: HbA1c improved for both URLi and lispro, and noninferiority was confirmed: estimated treatment difference (ETD) 0.06% (95% CI -0.05; 0.16). Mean change in HbA1c was -0.38% for URLi and -0.43% for lispro, with an end-of-treatment HbA1c of 6.92% and 6.86%, respectively. URLi was superior to lispro in controlling 1- and 2-h PPG excursions: 1-h ETD, -0.66 mmol/L (95% CI -1.01, -0.30); 2-h ETD, -0.96 mmol/L (-1.41, -0.52). Significantly lower PPG excursions were evident from 0.5 to 4.0 h postmeal with URLi treatment. There were no significant treatment differences in rates of severe or documented hypoglycemia (<3.0 mmol/L). Incidence of overall treatment-emergent adverse events was similar between treatments.

Conclusions: URLi compared with lispro in a basal-bolus regimen was confirmed to be noninferior for HbA1c and superior to lispro for PPG control in patients with type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT03214380.

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Figures

Figure 1
Figure 1
Mean HbA1c during study lead-in and 26-week treatment. Data are mean at screening and LSM ± SE for all other time points.
Figure 2
Figure 2
PPG excursions at week 26 with meal test. *P < 0.05 for between-treatment comparison; **P < 0.001 for between-treatment comparison. Data are LSM ± SE.
Figure 3
Figure 3
Ten-point SMBG profile at week 26. *P < 0.05 for between-treatment comparison. Data are LSM ± SE.
See this image and copyright information in PMC

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