Background and Aims

In BRIGHT (NCT02738151), Gla-300 showed similar glycaemic improvements to IDeg over 24 weeks in insulin-naïve participants with T2DM, with 24h hypoglycaemia incidence and rates being comparable between treatments during the maintenance and full-study periods, but lower with Gla-300 during the titration period. Older age and impaired renal function can increase hypoglycaemia risk; we evaluated the impact of baseline age and renal function on glycaemic and hypoglycaemia outcomes in BRIGHT.

Methods

BRIGHT was an open-label, actively-controlled, parallel-group trial in people with T2DM randomised to Gla-300 (N=466) or IDeg (N=463). This post-hoc analysis evaluated HbA_1c change and incidence and rates of 24h confirmed (≤3.9mmol/L [≤70mg/dL]) hypoglycaemia over 24 weeks, by age and renal function subgroups.

Results

HbA_1c reduction was greater with Gla-300 versus IDeg in participants ≥70 years, with significant heterogeneity of treatment effect between ≥70 and <70 years subgroups (p=0.0087). Hypoglycaemia incidence and rates were similar between treatments in both groups. Significant heterogeneity of treatment effect across renal function groups for HbA_1c reduction (p=0.015) reflected greater HbA_1c reduction with Gla-300 versus IDeg in patients with impaired renal function (eGFR <60 mL/min/1.73m²). Hypoglycaemia incidence was similar with Gla-300 and IDeg across all eGFR subgroups. Hypoglycaemia rates were similar between treatments in participants with eGFR <60 mL/min/1.73m², though lower with Gla-300 versus IDeg in those with normal renal function (eGFR ≥90 mL/min/1.73m²).

Conclusions

In people with T2DM at high risk of hypoglycaemia (≥70 years, impaired renal function), Gla-300 provided greater reductions in HbA_1c versus IDeg, without increased incidence or rates of hypoglycaemia.

Study sponsored by Sanofi

Background and Aims

Insulin glargine 300 U/mL (Gla-300) and insulin degludec 100 U/mL (IDeg-100) have shown slightly different pharmacokinetic/pharmacodynamic profiles; however, the first head-to-head randomised controlled trial in insulin-naïve people with type 2 diabetes (T2D) demonstrated similarity in clinical endpoints, except during the 0–12 week period when results were in favour of Gla-300 for anytime hypoglycaemia.

InRange aims to assess the clinical impact of Gla-300 and IDeg-100 in people with T1D by assessing primarily continuous glucose monitoring (CGM) endpoints.

Methods

Approximately 340 people with T1D aged 18–70 years, on a basal + mealtime insulin regimen for ≥1 year, and HbA_1c ≥7 % and <10 % will be included. Screening (1–2 weeks) will be followed by a 4-week run-in (background insulin treatment optimisation including 2-weeks baseline CGM) and a 12-week randomised treatment period after basal insulin switch to Gla-300 or IDeg-100 (titrated to the target glucose range without hypoglycaemia). During the randomised period, CGM will be performed at weeks 11–12 according to the most recent CGM consensus statement and ADA guidelines. The primary endpoint will be analysed using a mixed-effect model with repeated measures approach.

Results

Study ongoing

Conclusions

The objectives are to assess the percentage time in range for glucose (70–180 mg/dL [3.9–10 mmol/L]) (primary endpoint) at week 12, and glucose variability (reported as coefficient of variation [total, within day, between day]); in addition to other clinical outcomes including occurrence and frequency of hypoglycaemia (severe; documented symptomatic; and asymptomatic (<70 mg/dL [<3.9 mmol/L], <54 mg/dL [<3.0 mmol/L])).

Supported by:Sanofi, EudraCT: 2017-002756-91; NCT04075513