In a post hoc analysis of 3,765 patients across five ONWARDS trials, once-weekly insulin icodec showed consistent efficacy and low hypoglycemia rates regardless of whether patients were also taking GLP-1 receptor agonists or SGLT2 inhibitors.
No significant interactionsbetween icodec and background GLP-1 RA or SGLT2i use across 3,765 patients in five ONWARDS trials
What the researchers found
Across ONWARDS 1-5 (3,765 participants), 21.3% were using a GLP-1 RA and 36.9% were using an SGLT2i at baseline. There were no statistically significant treatment interactions by GLP-1 RA or SGLT2i subgroups for HbA1c change, body weight change (with one minor exception), weekly insulin dose, or achievement of HbA1c <7% without clinically significant hypoglycemia.
Rates of clinically significant or severe hypoglycemia were less than 1 episode per patient-year across all trials (except ONWARDS 4, a basal-bolus trial), regardless of GLP-1 RA/SGLT2i use. The efficacy and safety profile of icodec versus daily insulin was consistent across all subgroups.
Why it matters
Many diabetes patients today take GLP-1 drugs or SGLT2 inhibitors alongside insulin. Before prescribing a new once-weekly insulin, clinicians need to know it works well in combination with these background medications. This analysis provides the reassurance that switching to weekly icodec doesn't create unexpected interactions or reduce efficacy when patients are already on modern diabetes drug regimens.
How the study worked
Post hoc analysis of the randomized ONWARDS 1-5 trials. Participants with type 2 diabetes were analyzed by subgroups based on baseline GLP-1 RA and/or SGLT2i use. Treatment outcomes compared included HbA1c change, body weight change, weekly insulin dose, HbA1c target achievement, and hypoglycemia rates between icodec and daily basal insulin comparators.
What this study cannot tell us
This is a post hoc analysis, not a prospectively designed subgroup study, so the comparisons were not powered for the specific subgroups analyzed. The GLP-1 RA and SGLT2i user subgroups were defined by baseline use but the specific drugs and doses varied. The exception in ONWARDS 5 for body weight by SGLT2i use suggests some potential interactions that need further investigation. As with all subgroup analyses, results should be interpreted with caution.
How to read the evidence
This is a post hoc analysis of five randomized controlled trials (ONWARDS program), providing strong clinical evidence. While post hoc subgroup analyses are exploratory, the consistency across five separate trials strengthens the findings.
When this study was published
Published in 2025, this analysis supports the clinical integration of the recently approved once-weekly insulin icodec into existing multi-drug diabetes regimens.
The bigger picture
Once-weekly insulin icodec represents a paradigm shift in insulin therapy — from daily to weekly injections. As the diabetes treatment landscape increasingly involves multi-drug regimens (GLP-1 RAs + SGLT2i + insulin), demonstrating consistent efficacy across these combinations is essential for clinical adoption. This analysis from the landmark ONWARDS program supports icodec's integration into modern combination therapy.
Questions still open
- Would starting icodec simultaneously with a GLP-1 RA produce different results than adding it to established GLP-1 therapy?
- Does the ONWARDS 5 body weight finding with SGLT2i use represent a true interaction or a statistical artifact?
- How will icodec fit into the evolving treatment algorithms that increasingly prioritize GLP-1 RAs as first-line therapy?
Common questions
Can I take once-weekly insulin and a GLP-1 drug at the same time?
What is insulin icodec and how is it different?
Read the original research
Efficacy and hypoglycaemia outcomes with once-weekly insulin icodec versus once-daily basal insulin in type 2 diabetes according to baseline glucagon-like peptide-1 receptor agonist and sodium-glucose co-transporter-2 inhibitor use: A post hoc analysis of ONWARDS 1-5.
Diabetes, obesity & metabolism, 27(6), 3165-3175
Citation
Vilsbøll, Tina; Fu, Ariel; Kellerer, Monika; Kumar, Bharath; Søgaard, Stinne Byrholdt; Goldenberg, Ronald. (2025). Efficacy and hypoglycaemia outcomes with once-weekly insulin icodec versus once-daily basal insulin in type 2 diabetes according to baseline glucagon-like peptide-1 receptor agonist and sodium-glucose co-transporter-2 inhibitor use: A post hoc analysis of ONWARDS 1-5.. Diabetes, obesity & metabolism, 27(6), 3165-3175. https://doi.org/10.1111/dom.16328