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Once-weekly insulin icodec; Daily basal insulin; Type 2 diabetes; Randomized trial; Glycemic control; HbA鈧乧 reduction; Hypoglycemia; Insulin dosing; ONWARDS 3 trial; Insulin glargine U100; Insulin degludec; Clinical efficacy; Safety profile; Treatment adherence.

Introduction

Type 2 diabetes mellitus (T2DM) is a chronic condition characterized by insulin resistance and β-cell dysfunction, often necessitating insulin therapy for optimal glycemic control. Traditional daily basal insulin regimens, such as insulin glargine U100, have been widely used; however, they require daily injections, which can impact patient adherence and quality of life [1-5]. Insulin icodec, a novel long-acting basal insulin with a half-life of approximately one week, offers the potential to reduce the treatment burden by allowing for once-weekly administration. The ONWARDS 3 randomized trial aimed to compare the efficacy and safety of once-weekly insulin icodec with once-daily insulin degludec in adults with insulin-naive T2DM [6-10].

Discussion

The ONWARDS 3 trial was a multicenter, open-label, randomized controlled trial that enrolled 588 participants with insulin-naive T2DM. Participants were randomly assigned to receive either once-weekly insulin icodec or once-daily insulin degludec for 26 weeks. The primary endpoint was the change in HbA鈧乧 from baseline to week 26. Secondary endpoints included fasting plasma glucose levels, insulin dose requirements, and the incidence of hypoglycemic events.

At week 26, both insulin icodec and insulin degludec demonstrated significant reductions in HbA鈧乧 levels. The estimated treatment difference (ETD) between the two groups was −0.2 percentage points (95% CI, −0.3 to −0.1), favoring insulin icodec. This result confirmed noninferiority and suggested superiority of insulin icodec over insulin degludec. Fasting plasma glucose levels decreased similarly in both groups, with no significant difference between treatments. Additionally, the mean weekly insulin dose during the last two weeks of treatment was comparable between the two groups, indicating similar insulin requirements.

The safety profiles of insulin icodec and insulin degludec were generally similar. However, the incidence of combined level 2 or 3 hypoglycemic events was numerically higher in the insulin icodec group compared to the insulin degludec group (0.35 vs. 0.12 events per patient-year exposure; P = 0.01). Despite this, the overall rates of hypoglycemia remained low in both groups, with less than one event per patient-year exposure. No new safety concerns were identified during the trial.

The ONWARDS 3 trial provides evidence supporting the use of once-weekly insulin icodec as a viable alternative to daily basal insulin regimens in insulin-naive adults with T2DM. The comparable efficacy and safety profiles suggest that insulin icodec can effectively manage blood glucose levels while potentially improving patient adherence due to the reduced injection frequency. These findings align with previous studies demonstrating the benefits of long-acting insulin analogues in T2DM management.

Conclusion

In conclusion, the ONWARDS 3 trial demonstrated that once-weekly insulin icodec is noninferior and possibly superior to once-daily insulin degludec in reducing HbA鈧乧 levels in insulin-naive adults with T2DM. Both treatments were associated with similar safety profiles, with low rates of hypoglycemia. The introduction of insulin icodec offers a promising option for simplifying diabetes management and enhancing patient adherence. Further long-term studies are warranted to confirm these findings and assess the impact of once-weekly insulin icodec on long-term clinical outcomes in T2DM.

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