ONWARDS and upwards for basal insulin

Abstract

In this issue of The Lancet, Chantal Mathieu and colleagues present the findings of ONWARDS 4, a phase 3 randomised, open-label, treat-to-target, non-inferiority trial comparing the novel once-weekly insulin icodec (n=291) versus once-daily insulin glargine U100 (n=291) in people with long-standing type 2 diabetes on basal-bolus insulin therapy. 1 Mathieu C Ásbjörnsdóttir B Bajaj HS et al. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial. Lancet. 2023; (published online May 5.)https://doi.org/10.1016/S0140-6736(23)00520-2 Summary Full Text Full Text PDF Google Scholar The trial was conducted in Belgium, India, Italy, Japan, Mexico, the Netherlands, Romania, Russia, and the USA. The participants had a mean duration of type 2 diabetes of 17·1 years (SD 8·4), a mean age at baseline of 59·8 years (SD 10·0), and 304 of the 582 participants were men and 278 were women. The primary outcome in ONWARDS 4 was met, with both icodec and glargine U100 shown to be equally effective at reducing HbA1c from baseline by week 26 (estimated mean change in HbA1c −1·16 percentage points in the icodec group [baseline 8·29%] and −1·18 percentage points in the glargine U100 group [baseline 8·31%]; estimated treatment difference 0·02 percentage points [95% CI −0·11 to 0·15], p<0·0001). Given the age, duration of diabetes, and number of comorbidities of participants, the percentage of time spent with glucose concentrations within the target range of 70–180 mg/dL (3·9–10·0 mmol/L) by week 26 (ie, trial end) was impressive; 66·9% in the icodec group and 66·4% in the glargine group. In addition, the percentage of time spent with glucose concentrations less than 54 mg/dL (<3·0 mmol/L) was low, not differing significantly between the groups (0·7% for the icodec group and 0·6% for the glargine U100 group). Overall, combined level 2 and 3 hypoglycaemia rates were similar between treatment groups, there were no significant differences in weight gain, and no new safety signals emerged. These findings would suggest that once-weekly icodec is a viable therapeutic option for people with type 2 diabetes on a basal-bolus insulin regimen, and, perhaps more importantly, heralds the introduction of once-weekly insulins into clinical practice, an exciting and welcome addition to the insulin family. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trialIn people with long-standing type 2 diabetes on a basal-bolus regimen, once-weekly icodec showed similar improvements in glycaemic control, with fewer basal insulin injections, lower bolus insulin dose, and with no increase in hypoglycaemic rates compared with once-daily glargine U100. Key strengths of this trial include the use of masked continous glucose monitoring; the high trial completion rate; and the inclusion of a large, diverse, and multinational population. Limitations include the relatively short trial duration and the open-label design. Full-Text PDF