ONWARDS 3
Trial question
What is the role of once-weekly insulin icodec in adult patients with insulin-naïve T2DM?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
37.0% female
63.0% male
N = 588
588 patients (219 female, 369 male).
Inclusion criteria: adult patients with T2DM treated with any noninsulin glucose-lowering agents with HbA1c of 7-11%.
Key exclusion criteria: any episodes of diabetic ketoacidosis within 90 days prior to the day of screening; uncontrolled/unstable diabetic retinopathy or maculopathy; MI, stroke, hospitalization for unstable angina pectoris, or TIA within 180 days prior to the day of screening.
Interventions
N=294 icodec (once-weekly icodec and once-daily placebo via subcutaneous injections).
N=294 degludec (once-daily degludec and once-weekly placebo via subcutaneous injections).
Primary outcome
Reduction in hemoglobin A1c level at week 26
1.6%
1.4%
1.6 %
1.2 %
0.8 %
0.4 %
0.0 %
Icodec
Degludec
Significant
increase ▲
NNT = 499
Significantly greater reduction in HbA1c level at week 26 (1.6% vs. 1.4%; AD 0.2%, 95% CI 0.1 to 0.3).
Secondary outcomes
No significant difference in reduction in fasting plasma glucose at week 26 (54 mg/dL vs. 54 mg/dL).
No significant difference in mean insulin dose from week 24 to 26 (204 U/week vs. 187 U/week; RR 1.1, 95% CI 0.98 to 1.22).
No significant difference in improvement in mean body weight (2.8 kg vs. 2.3 kg; AD 0.46 kg, 95% CI -0.19 to 1.1).
Safety outcomes
No significant difference in combined level 2 or level 3 hypoglycemic episodes at week 31.
Significant difference in combined level 2 or level 3 hypoglycemic episodes at week 26 (0.35 per patient-year exposure vs. 0.12 per patient-year exposure).
Conclusion
In adult patients with T2DM treated with any noninsulin glucose-lowering agents with HbA1c of 7-11%, icodec was superior to degludec with respect to reduction in HbA1c level at week 26.
Reference
Ildiko Lingvay, Marisse Asong, Cyrus Desouza et al. Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes: The ONWARDS 3 Randomized Clinical Trial. JAMA. 2023 Jul 18;330(3):228-237.
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