Basal insulin peglispro versus insulin glargine in insulin-naïve type 2 diabetes: IMAGINE 2 randomized trial

Abstract

Aims: To compare, in a double-blind, randomized, multi-national study, 52- or 78-week treatment with basal insulin peglispro or insulin glargine, added to pre-study oral antihyperglycaemic medications, in insulin-naïve adults with type 2 diabetes.

Material and methods: The primary outcome was non-inferiority of peglispro to glargine with regard to glycated haemoglobin (HbA1c) reduction (margin = 0.4%). Six gated secondary objectives with statistical multiplicity adjustments focused on other measures of glycaemic control and safety. Liver fat content was measured using MRI, in a subset of patients.

Results: Peglispro was non-inferior to glargine in HbA1c reduction [least-squares (LS) mean difference: -0.29%, 95% confidence interval (CI) -0.40, -0.19], and had a lower nocturnal hypoglycaemia rate [relative rate 0.74 (95% CI 0.60, 0.91); p = .005), more patients achieving HbA1c <7.0% without nocturnal hypoglycaemia [odds ratio (OR) 2.15 (95% CI 1.60, 2.89); p < .001], greater HbA1c reduction (p < .001), and more patients achieving HbA1c<7.0% [OR 1.97 (95% CI 1.57, 2.47); p < .001]. Total hypoglycaemia rate and fasting serum glucose did not achieve statistical superiority. At 52 weeks, peglispro-treated patients had higher triglyceride (1.9 vs 1.7 mmol/L). alanine transaminase (34 vs 27 IU/L), and aspartate transaminase levels (27 vs 24 IU/L). LS mean liver fat content was unchanged with peglispro at 52 weeks but decreased 3.1% with glargine [difference: 2.6% (0.9, 4.2); p = .002]. More peglispro-treated patients experienced adverse injection site reactions (3.5% vs 0.6%, p < .001).

Conclusions: Compared with glargine at 52 weeks, peglispro resulted in a statistically superior reduction in HbA1c, more patients achieving HbA1c targets, less nocturnal hypoglycaemia, no improvement in total hypoglycaemia, higher triglyceride levels, higher aminotransferase levels, and more injection site reactions.

Keywords: BIL; basal insulin peglispro; insulin therapy; insulin-naïve; type 2 diabetes.

Figure 1

HbA1c, insulin dose and weight. Graphs show values for basal insulin peglispro (BIL; solid line, black circles) and insulin glargine (GL; dashed line, white circles). Week 0 was the randomization time point. The gap between values for weeks 52 and 65 indicates that these values were derived from different populations. Data up to week 52 are for the entire population (N = 1538); data thereafter are for the 78‐week cohort (N = 920). Data were analysed using mixed‐model repeated measures. LS mean values are shown. Error bars indicate 95% CIs; p‐values for between‐group differences and the number of patients assessed in each treatment group are shown at key time points below each graph. HbA1c (%; panel A), insulin dose (U; panel B), change in weight from baseline (kg; panel C).

Figure 2

Cumulative rates of hypoglycaemia. (A) Total hypoglycaemia. (B) Nocturnal hypoglycaemia. For both panels, “lines” are continuous data points indicating rates of hypoglycaemia throughout the study. Black lines indicate basal insulin peglispro (BIL). Grey lines indicate insulin glargine (GL). The number of episodes of hypoglycaemia per 100 patients was calculated and plotted against actual time, rather than visit dates. Because variability was allowed in the timing of study visits, hypoglycaemia was recorded up to 82 weeks. No inferential statistical analyses were conducted. The number of patients assessed in each treatment group is shown at key time points below each graph.

Figure 3

Change in lipids over time. A. Total Cholesterol, B. HDL Cholesterol, C. Triglycerides, 4. LDL Cholesterol Graphs show values for basal insulin peglispro (BIL; solid line, black circles) and insulin glargine (GL; dashed line, white circles). The gap between values for weeks 52 and 65 indicates these values are derived from different populations. Data up to week 52 are for the entire population (N = 1538); data for weeks 65 and 78 are for the 78‐week cohort (N = 920). Data were analysed using mixed‐model repeated measures. LS mean values are shown. Error bars indicate 95% CIs; p values for between‐group differences and the number of patients assessed in each treatment group are shown at key time points below each graph.