Efficacy and safety of once-weekly insulins: Meta-analysis

In this systematic review and meta-analysis, the authors evaluated the efficacy and safety of once-weekly insulin analogues in adults with type 2 diabetes. Nine phase 2–3 randomised controlled trials were included in the analysis. A total of 1722 participants (80%) received insulin icodec while 410 (20%) received insulin efsitora alfa. They were compared with 1830 controls who received once-daily insulin glargine or degludec.

HbA_1c at baseline ranged from 7.8% to 8.6%. Over follow-up ranging from 21 to 52 weeks, the once-weekly insulin group had a greater reduction in mean HbA_1c than the daily insulin group (mean difference –0.13%). This result was largely driven by insulin icodec, as efsitora alfa was associated with a non-significant change in HbA_1c. The weekly insulin group also had a small but significant increase in Time in Range (mean difference 3.54%).

The odds of achieving an HbA_1c below 7.0% was significantly greater in the weekly insulin group (odds ratio [OR] 1.30), and icodec users were more likely to achieve an HbA_1c below 6.5% (OR 1.75). However, icodec was associated with a significant increase in body weight (mean difference 0.57 kg), although the increase was not significant for weekly insulins as a group.

The rate of serious adverse events was similar between weekly and daily insulins, while there was a borderline-significant increase in the odds of any adverse events in weekly insulin users (OR 1.51; 95% CI 0.97–2.35).

The risk of level 1 hypoglycaemia was significantly higher with weekly insulin (OR 1.30) whilst, in contrast, the risk of level 2–3 hypoglycaemia was significantly lower (OR 0.74).

These results are limited by the small number of studies included in the meta-analysis, the open-label designs of most of the studies, differences in follow-up duration and dose titration algorithms between the trials and the strict eligibility criteria for participants. Nonetheless, the results suggest that once-weekly insulins may offer similar or superior glycaemic control to daily insulins, albeit with some greater weight gain, and with a similar safety profile.

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