ONWARDS 8: icodec plus semaglutide in T2D

A Phase 3b trial published in Diabetes, Obesity and Metabolism on 1 July 2026 examined what happens when clinicians layer a weekly GLP-1 receptor agonist onto a weekly basal insulin regimen in adults with type 2 diabetes (T2D) whose glucose control is still inadequate. ONWARDS 8 (NCT05813912) is the first trial in the ONWARDS programme to test this specific combination: once-weekly insulin icodec intensified with once-weekly semaglutide^[1].

Insulin icodec (brand name Awiqli, developed by Novo Nordisk) is a long-acting basal insulin authorised by the EMA in May 2024 for adults with diabetes mellitus^[2]. Its once-weekly dosing mirrors the administration schedule of semaglutide (Ozempic), making the combination a potential step towards a fully once-weekly injectable regimen for T2D management.

Trial design

ONWARDS 8 enrolled 148 adults with T2D and HbA1c between 7.5% and 10.5% who were already on daily basal insulin and had not previously used a GLP-1 receptor agonist. The trial ran in two consecutive phases: a 26-week run-in during which participants were switched to insulin icodec and dose-optimised, followed by a 26-week intensification period in which semaglutide was added at a starting dose and titrated upwards according to tolerability^[1]. The design was single-arm, open-label, and treat-to-target. Of the 148 participants who entered the icodec run-in, 94 initiated semaglutide and completed the intensification phase.

Key efficacy findings

The primary outcome was change in HbA1c from the start of the semaglutide intensification period to week 26. Mean HbA1c fell by 1.23 percentage points (from 7.88% to 6.66%; 95% CI for change: -1.39 to -1.07; p < 0.0001)^[1]. The 7-point self-measured blood glucose profile dropped by 1.72 mmol/L over the same period.

Body weight decreased by 3.85 kg during the semaglutide intensification phase^[1]. This is consistent with the weight-reduction profile semaglutide produces as a GLP-1 receptor agonist; the effect is smaller than figures from dedicated obesity trials because the patient population here already had T2D and had been on insulin, which independently constrains weight loss. The GLP-1 weight-loss differential between diabetic and non-diabetic populations is explored in a separate article.

Insulin dosing adjusted noticeably during the add-on period. Participants experienced a mean 24% relative reduction in their weekly icodec dose; 69.1% had their icodec dose reduced by at least 20%^[1]. This is an expected pharmacodynamic interaction: semaglutide lowers postprandial and fasting glucose through independent mechanisms, so the insulin requirement decreases when a GLP-1 agonist is added.

Hypoglycaemia

Hypoglycaemia is the central safety concern when combining a GLP-1 receptor agonist with any basal insulin. In ONWARDS 8, the rate of clinically significant or severe hypoglycaemia was 0.24 episodes per person-year during the semaglutide intensification period^[1]. The trial protocol included a proactive dose-reduction algorithm for icodec when semaglutide was initiated, which likely explains the low event rate. No separate breakdown by nocturnal versus daytime events is reported in the abstract.

Where ONWARDS 8 fits in the ONWARDS programme

The ONWARDS programme tested insulin icodec across a range of comparators and patient populations. Earlier trials, ONWARDS 1 through 7, established the efficacy and safety of icodec against daily basal insulins (glargine U100, degludec) in both insulin-naive and insulin-experienced adults with T2D, and in a dedicated phase 3 trial in type 1 diabetes^[3]. ONWARDS 8 extends the programme into combination territory, asking whether the convenience of a once-weekly basal insulin is maintained and whether glycaemic control can be deepened by pairing it with a once-weekly GLP-1 agonist rather than adding a second daily injection.

A mini-review of once-weekly insulins published in Frontiers in Endocrinology in 2025 characterised insulin icodec as the lead agent in a small but growing field where dosing frequency is being aligned with the weekly schedule that GLP-1 receptor agonists like semaglutide and tirzepatide have normalised^[3].

Limitations to read alongside the results

ONWARDS 8 is single-arm, so there is no randomised comparator. Readers cannot draw conclusions about whether the combination is better than, say, adding daily semaglutide to daily basal insulin, or maintaining icodec without intensification at all. The 94-person semaglutide-treated cohort is small for a Phase 3b designation. The treat-to-target protocol and open-label design introduce the usual caveats about practitioner behaviour influencing outcome^[1]. The 26-week intensification window is also relatively short for detecting late-onset hypoglycaemia patterns.

Sponsor affiliation is relevant here. Two of the six authors (Stinne Byrholdt Søgaard and Sara Kehlet Watt) are listed with Novo Nordisk A/S affiliation^[1], the manufacturer of both insulin icodec and semaglutide. This does not invalidate the data, but it is standard practice to note industry involvement when interpreting trial results.

What this means for clinical practice

ONWARDS 8 does not change guidelines on its own. What it does is provide Phase 3b-level evidence that the once-weekly combination is feasible and that the hypoglycaemia risk can be managed with proactive icodec dose adjustment when semaglutide is introduced. Prescribers who are already maintaining patients on icodec and considering whether to add a GLP-1 agonist now have a structured dataset on the glucose and weight trajectory to reference in that conversation^[1].

This article is for informational purposes only and does not constitute medical advice. Consult a healthcare provider before making any treatment decision.