Effectiveness and safety of insulin glargine 300 U/mL in insulin-naïve individuals according to diabetes duration: Results from the REALI European pooled data analysis

Abstract

Aim: To evaluate the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) initiation according to diabetes duration (DD).

Materials and methods: We analysed patient-level data from 2381 insulin-naïve individuals with type 2 diabetes (T2D), of whom 2349 (98.7%) were treated with Gla-300 for 24 weeks. Of the 2381 participants, 1048 (44.0%) had a DD of less than 8 years and 1333 (56.0%) had a DD of 8 years or longer. We further analysed the subgroups of participants having a DD of less than 4 years (N = 450), 4-8 years (N = 598), 8-12 years (N = 627) and 12 years or longer (N = 706).

Results: Mean ± standard deviation age was 60.2 ± 9.0 years in participants with a DD less than 8 years and 64.2 ± 8.8 years in those with a DD of 8 years or longer. At 24 weeks of Gla-300 therapy, HbA1c improved with a least-squares (LS) mean change from baseline of -1.88% (95% confidence interval [CI], -1.95 to -1.80) and -1.71% (95% CI, -1.77 to -1.65), respectively, resulting in a LS mean difference between groups of 0.17% (95% CI, 0.07 to 0.26; P = .0005). In the subgroup analysis, LS mean HbA1c reduction from baseline to week 24 was highest in participants with a DD of less than 4 years and lowest in participants with a DD of 12 years or longer. Overall, incidences of symptomatic and severe hypoglycaemia were low, irrespective of DD, without body weight changes.

Conclusions: Gla-300 was effective and safe in insulin-naïve individuals with T2D, regardless of DD. Improvement in HbA1c was greater when Gla-300 was initiated in participants with a DD of less than 4 years, although the difference between the groups was modest.

Keywords: Gla‐300; diabetes duration; insulin glargine 300 U/mL; insulin‐naïve; type 2 diabetes.

FIGURE 1

Mean HbA1c and LS mean change (95% CI) in HbA1c from baseline to week 24 of Gla‐300 treatment according to diabetes duration, between A, The groups with diabetes durations of < 8 and ≥ 8 years, and B, The subgroups with diabetes durations of < 4, 4‐8, 8‐12 and ≥ 12 years. *The LS mean changes in HbA1c from baseline to weeks 12 and 24 were evaluated using a MMRM, with fixed categorical effects of visit, subgroup category and subgroup category‐by‐visit interaction, as well as continuous fixed covariates of baseline HbA1c, age, baseline BMI, baseline HbA1c value‐by‐visit interaction, age value‐by‐visit interaction and baseline BMI value‐by‐visit interaction. Study effect is considered as a fixed categorical effect in the analysis. A, The LS mean difference between participants with diabetes durations of < 8 and ≥ 8 years was 0.17% (95% CI, 0.07% to 0.26%; P = .0005). B, The LS mean difference between participants with diabetes durations of < 4 and ≥ 12 years was clinically significant, and the 95% CIs did not overlap between the two subgroups, suggesting a statistically significant difference. BMI, body mass index; CI, confidence interval; DD, diabetes duration; Gla‐300, insulin glargine 300 U/mL; LS, least‐squares; MMRM, mixed model for repeated measures.

FIGURE 2

Percentage of participants achieving HbA1c targets of < 7.0%, < 7.5% and < 8.0% at week 24 of the study. A Chi‐square test performed for each of the three targets showed a statistically significant difference between groups with diabetes durations of less than 8 years and of 8 years or longer at week 24 for the target HbA1c < 7.0% (P = .015), whereas there was no statistically significant difference for the targets of HbA1c < 7.5% and < 8.0% (P = .183 and P = .965, respectively)

FIGURE 3

Mean Gla‐300 daily dose (in U/kg/day) at baseline and at weeks 12 and 24. Gla‐300, insulin glargine 300 U/mL.