ONWARDS 1
Trial question
Is once-weekly insulin icodec superior to once-daily insulin glargine U100 in insulin-naïve patients with T2DM?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
43.0% female
57.0% male
N = 984
984 patients (426 female, 558 male).
Inclusion criteria: adult patients with T2DM who had not previously received insulin.
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=492 icodec (at a starting dose of 70 U per week).
N=492 glargine U100 (at a starting dose of 10 U per day).
Primary outcome
Reduction in glycated hemoglobin level at week 52
1.55%
1.35%
1.6 %
1.2 %
0.8 %
0.4 %
0.0 %
Icodec
Glargine
U100
Significant
increase ▲
NNT = 500
Significantly greater reduction in glycated hemoglobin level at week 52 (1.55% vs. 1.35%; AD 0.19%, 95% CI 0.03 to 0.36).
Secondary outcomes
Significant increase in the rate of time spent in glycemic range of 70-180 mg/dL in week 48 to 52 (71.9% vs. 66.9%; AD 4.27%, 95% CI 1.92 to 6.62).
No significant difference in reduction in fasting plasma glucose level at week 52 (60.32 mg/dL vs. 60.08 mg/dL; AD 0.24 mg/dL, 95% CI -4.89 to 4.41).
Significant increase in glycated hemoglobin level < 7% at week 52 (57.6% vs. 45.4%; OR 1.63, 95% CI 1.24 to 2.14).
Safety outcomes
No significant differences in adverse events, clinically significant hypoglycemic events.
Conclusion
In adult patients with T2DM who had not previously received insulin, icodec was superior to glargine U100 with respect to reduction in glycated hemoglobin level at week 52.
Reference
Julio Rosenstock, Stephen C Bain, Amoolya Gowda et al. Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin. N Engl J Med. 2023 Jul 27;389(4):297-308.
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