COMBINE 1
Trial question
What is the effect of once-weekly combination therapy with basal insulin icodec and semaglutide (IcoSema) in patients with inadequately controlled T2DM receiving daily basal insulin therapy?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
38.0% female
62.0% male
N = 1291
1291 patients (492 female, 799 male).
Inclusion criteria: adult patients with inadequately controlled T2DM on daily basal insulin therapy.
Key exclusion criteria: anticipated initiation or change in concomitant medication known to affect weight or glucose metabolism; any episodes of diabetic ketoacidosis within 90 days; pancreatitis within 180 days; NYHA Class IV HF; recurrent severe hypoglycemic episodes within the last year; uncontrolled and potentially unstable diabetic retinopathy or maculopathy; pregnancy or lactation.
Interventions
N=646 basal insulin icodec plus semaglutide (IcoSema) (once-weekly subcutaneous injections of insulin icodec 700 U/mL and semaglutide 2 mg/mL for 52 weeks).
N=645 basal insulin icodec only (once-weekly subcutaneous injections of insulin icodec 700 U/mL for 52 weeks).
Primary outcome
Mean reduction in hemoglobin A1c at week 52
1.55%
0.89%
1.6 %
1.2 %
0.8 %
0.4 %
0.0 %
Basal insulin icodec plus semaglutide
(IcoSema)
Basal insulin icodec
only
Significant
increase ▲
NNT = 151
Significantly greater reduction in mean HbA1c at week 52 (1.55% vs. 0.89%; MD 0.66, 95% CI 0.57 to 0.76).
Secondary outcomes
Significant decrease in clinically significant or severe hypoglycemia at week 57 (0.14 episodes / p-y of exposure vs. 0.63 episodes / p-y of exposure; RR 0.22, 95% CI 0.14 to 0.36).
Safety outcomes
No significant differences in serious adverse events, death.
Conclusion
In adult patients with inadequately controlled T2DM on daily basal insulin therapy, basal insulin icodec plus semaglutide (IcoSema) was superior to basal insulin icodec only with respect to mean reduction in HbA1c at week 52.
Reference
Chantal Mathieu, Francesco Giorgino, Sin Gon Kim et al. Once‑weekly IcoSema versus once‑weekly insulin icodec in type 2 diabetes management (COMBINE 1): an open‑label, multicentre, treat‑to‑target, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2025 Jun 4:S2213-8587(25)00096-8. Online ahead of print.
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