Key points How does insulin Icodec given once a week compare with insulin Degludec given once a day in terms of effectiveness in lowering glucose (hemoglobin A 1c [HbA 1c]) in people with type 2 diabetes without prior treatment ? insulin? Findings In this randomized, double-blind, double-dummy trial involving 588 people with type 2 diabetes, the estimated mean change in HbA 1c from baseline to week 26 was non-inferior with Icodec insulin (−1.6 percentage points) compared to insulin Degludec (−1.4 percentage points), with confirmed statistical superiority (estimated treatment difference, −0.2 percentage points). Meaning The results demonstrate the effectiveness of treatment with insulin icodec once a week in people with type 2 diabetes without previous insulin treatment. |
Summary
Importance
Once-weekly insulin Icodec could provide a simpler dosing alternative to daily basal insulin in people with type 2 diabetes.
Aim
To evaluate the efficacy and safety of once-weekly insulin Icodec versus once-daily insulin Degludec in insulin-naïve people with type 2 diabetes.
Design, environment and participants
Randomized, double-blind, non-inferiority, treatment-to-target phase 3 trial conducted between March 2021 and June 2022 at 92 sites in 11 countries in adults with type 2 diabetes treated with any hypoglycemic agent other than insulin with hemoglobin A 1c (HbA 1c) of 7%-11% (53-97 mmol/mol).
Interventions
Participants were randomly assigned in a 1:1 ratio to receive Icodec once a week and placebo once a day (Icodec group; n = 294) or Degludec once a day and placebo once a week (Degludec group ; n = 294).
Main results and measures
The primary endpoint was the change in HbA 1c from baseline to week 26 (margin of noninferiority, 0.3% percentage points). Secondary endpoints included change in fasting plasma glucose from baseline to week 26, mean weekly insulin dose during the last 2 weeks of treatment, change in body weight from baseline to week 26, and the number of levels 2 (clinically significant; glucose level <54 mg). /dL) and level 3 (severe; requires outside assistance for recovery) episodes of hypoglycemia.
Results
Among 588 randomized participants (mean [SD] age, 58 [10] years; 219 [37%] women), 564 (96%) completed the trial. The mean HbA 1c level decreased from 8.6% (observed) to 7.0% (estimated) at 26 weeks in the Icodec group and from 8.5% (observed) to 7.2% (estimated) in the Degludec group (estimated treatment difference [ETD], − 0.2 [95% CI, −0.3 to −0.1] percentage points), confirming noninferiority ( p < 0.001) and superiority (p = 0.002).
There was no significant difference between the Icodec and Degludec groups for change in fasting plasma glucose from baseline to week 26 (ETD, 0 [95% CI, -6 to 5] mg/dL; P = 0.90 ), mean weekly insulin dose during the last 2 weeks of treatment, or body weight change from baseline to week 26 (2.8 kg vs. 2.3 kg; ETD, 0.46 [95% CI] −0.19 to 1.10] kg; P = .17).
The pooled rates of level 2 or 3 hypoglycemia were numerically higher in the Icodec group than in the Degludec group from weeks 0 to 31 (0.31 vs. 0.15 events per exposure per patient-year; P = 0.11) and statistically higher in the icodec group from week 0 to 31. 26 (0.35 vs. 0.12 events per exposure-patient-year; P = 0.01).
Conclusions and relevance Among insulin-naïve people with type 2 diabetes, Icodec once weekly demonstrated a greater reduction in HbA 1c than Degludec once daily after 26 weeks of treatment, with no difference in weight change and a higher rate discharge of combined levels of hypoglycemia 2 or 3 events in the setting of less than 1 event per patient-year exposure in both groups. |
ClinicalTrials.gov Trial Registration Identifier: NCT04795531
