Early Real‐World Implementation of Once‐Weekly Insulin Icodec in Type 2 Diabetes

The ONWARDS Phase 3 programme demonstrated that once-weekly insulin icodec achieves glycaemic control comparable to, or in some settings, superior to, once-daily basal insulin analogues in type 2 diabetes (T2DM) [1-5]. However, the transition from controlled trial settings to routine clinical practice raises practical questions regarding titration flexibility, early safety and use in multimorbid patients—areas not fully captured in randomised protocols. To provide initial insights into real-world use, we describe our experience with a small cohort of patients with insulin icodec in a clinically complex T2DM population managed in routine care. Ten consecutive male patients with T2DM and a clinical indication or intensification of basal insulin therapy (HbA1c > 7.0%) initiated once-weekly insulin icodec at a tertiary referral centre and were followed for 12 weeks. Insulin icodec was selected to evaluate the feasibility, safety and patient acceptance of a once-weekly regimen in routine practice. Unlike trial populations, this cohort reflected everyday clinical heterogeneity: advanced age, long-standing disease (up to 30 years), cardiovascular disease, chronic kidney disease—including severe impairment—active malignancy and polypharmacy. Five patients were insulin-naïve; the remainder transitioned from daily basal or basal–bolus regimens (Table 1). Insulin icodec was initiated in accordance with the approved prescribing information [6], but titration was individualised pragmatically. While ONWARDS protocols applied fixed ±20 IU weekly adjustments [1-4], we implemented ±10–20 IU modifications according to glycaemic trends, frailty and comorbidity burden (Figure S1). In one patient, a loading dose was administered to facilitate earlier steady-state exposure (Table S1), consistent with pharmacokinetic data demonstrating stable week-long activity [7]. This approach reflects real-world decision-making and directly addresses a key barrier to adoption: whether trial algorithms must be applied rigidly in complex patients. Glycaemic improvement was rapid and clinically meaningful. HbA1c declined from 8.5% ± 1.0% to 7.1% ± 0.7% at 12 weeks (p = 0.01) (Figure 1). Fasting plasma glucose decreased from 178.9 ± 25.2 mg/dL to 119.8 ± 17.8 mg/dL (p = 0.01) (Figure S1), with most of the reduction achieved within the first four weeks as doses stabilised (Table 2). Among continuous glucose monitoring users, time in range exceeded 70% in the majority, accompanied by reduced glycaemic variability (Figure S2). Reassuringly, no severe hypoglycaemia occurred. One patient reported sporadic mild events. Structured post-first-dose monitoring did not reveal clinically significant acute glucose declines—an observation of practical importance given theoretical concerns regarding early insulin stacking with ultra–long-acting formulations. Body weight remained stable, consistent with trial data [1, 3, 8]. Treatment satisfaction improved markedly among patients previously treated with daily basal insulin, who reported greater convenience and reduced treatment burden following the switch. All patients expressed willingness to continue therapy long-term (Figure S3). Our experience provides preliminary observations beyond confirmatory efficacy while acknowledging the small sample size. First, once-weekly insulin therapy appeared feasible and reasonably stable even in patients with substantial comorbidity burden, including advanced renal impairment—groups often underrepresented in randomised trials. One patient later reclassified as having latent autoimmune diabetes in adults (LADA) did not exhibit glycaemic instability during short-term follow-up. Although no inference can be made beyond this observation, it underscores the heterogeneity encountered in practice. Second, individualised titration using smaller dose adjustments appeared compatible with meaningful glycaemic improvements, suggesting that flexible approaches may be considered in frail or high-risk individuals. Fear of hypoglycaemia remains a major driver of therapeutic inertia in T2DM [9]; pragmatic titration strategies may therefore have a disproportionate impact on implementation success. Third, among patients transitioning from daily basal insulin who completed the treatment satisfaction questionnaire, most reported improved convenience and reduced perceived treatment burden. While these findings are descriptive, they suggest improved patient-reported outcomes, in line with the data reported by the ONWARDS trials [2, 4]. Beyond cost-effectiveness [10], less frequent injections may offer a behavioural advantage, in addition to their pharmacological benefits, potentially improving long-term adherence [11]. This report is limited by its small sample size, short duration and single-centre design. Nonetheless, early real-world evidence serves a complementary role to randomised trials by informing how therapies perform under less controlled conditions [11]. As once-weekly insulin moves from trial validation to clinical integration, practical experience becomes essential to guide safe and confident adoption. In summary, our findings suggest that once-weekly insulin icodec can be effectively and safely implemented in routine T2DM care, including in clinically complex patients, when individualised titration is applied. By substantially reducing injection burden without compromising metabolic control, weekly basal insulin may help address persistent barriers to insulin initiation and persistence. Larger multicentre observational studies are warranted to refine titration strategies and define patient subgroups most likely to benefit from this therapeutic shift. The authors have nothing to report. The authors declare no conflicts of interest. Data are availalbe upon request to the corresponding author. The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/dom.70652. Table S1: Individual patient characteristics at baseline and follow-up. Figure S1: Time course of glycemic control in 10 patients with type 2 diabetes mellitus treated with once-weekly insulin icodec. Left panel: Individual changes in weekly insulin icodec dose over the 12-week follow-up period. Right panel: Individual trends in fasting morning blood glucose levels over time, as measured by capillary glucose testing. Figure S2: Longitudinal trends in continuous glucose monitoring-derived glycemic metrics for individual patients. Metrics include time in range (TIR), time above range (TAR), coefficient of variation (CV) and glucose management indicator (GMI). Figure S3:. Diabetes Treatment Satisfaction Questionnaire (DTSQ) scores. Upper panels. Individual patient scores for each DTSQ item. Lower panels. Total DTSQ scores for each patient and grouped before-after analysis following initiation of insulin icodec (right panel). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.