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

Abstract

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 METHODSThis 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 5 336) or lispro (n 5 337) 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 HbA 1c from baseline to 26 weeks (noninferiority margin 0.4%), with multiplicityadjusted objectives for postprandial glucose (PPG) excursions during a standardized meal test. RESULTSHbA 1c improved for both URLi and lispro, and noninferiority was confirmed: estimated treatment difference (ETD) 0.06% (95% CI 20.05; 0.16). Mean change in HbA 1c was 20.38% for URLi and 20.43% for lispro, with an end-of-treatment HbA 1c of 6.92% and 6.86%, respectively. URLi was superior to lispro in controlling 1and 2-h PPG excursions: 1-h ETD, 20.66 mmol/L (95% CI 21.01, 20.30); 2-h ETD, 20.96 mmol/L (21.41, 20.52). 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. CONCLUSIONSURLi compared with lispro in a basal-bolus regimen was confirmed to be noninferior for HbA 1c and superior to lispro for PPG control in patients with type 2 diabetes.There have been many advances in the treatment of type 2 diabetes; however, reaching glycemic goals remains a challenge. Only ;30% of patients with type 2 diabetes are able to attain an HbA 1c target of ,7% even with insulin therapy (1). The overall proportion of patients reaching HbA 1c ,7% or individualized HbA 1c targets has not improved during the past decade (2). HbA 1c provides an integrated

Ultra-Rapid Lispro Efficacy and Safety Compared to Humalog® in Japanese Patients With Type 2 Diabetes: PRONTO-T2D Subpopulation Analysis

“…The PRONTO-T2D study demonstrated that URLi is non-inferior to lispro in terms of change in HbA1c following 26 weeks of treatment and that URLi is superior to lispro at reducing 1-and 2-h PPG excursions during the meal test [21]. In our subpopulation analysis of Japanese patients with T2DM, URLi demonstrated effective glycemic control when used in combination with basal insulin, with an acceptable safety profile.…”

“…The efficacy analysis was conducted as previously described for the overall population [21]. These methods were applied to the Japanese population in a prespecified subset analysis, although statistical power was not taken into consideration, and p values are provided as a reference.…”

“…The primary study endpoint was the change in HbA1c from baseline to week 26. For the overall patient population of the PRONTO-T2D trial, non-inferiority of URLi to lispro was confirmed in the change in HbA1c from baseline to week 26 [21] (the upper 95% confidence interval [CI] of least squares mean [LSM] difference was \ 0.4%, defined as the prespecified non-inferiority criteria for the overall population).…”

“…The study design has been described previously [21]. Briefly, adults with clinically diagnosed T2DM (based on the World Health Organization classification [22]) for at least 1 year prior to screening and with HbA1c levels between 7.0% (53.0 mmol/mol) and 10.0% (85.8 mmol/mol) inclusive were eligible to participate.…”

“…PRONTO-T2D was a recent, prospective, randomized, double-blind phase 3 trial in adults with T2DM which compared URLi to lispro, in combination with insulin glargine or insulin degludec [21]. This pivotal study demonstrated that URLi was non-inferior to lispro in maintaining glycemic control [21]. Here we describe a Japanese subpopulation analysis of the PRONTO-T2D trial.…”