Efficacy and safety of once‐weekly insulin icodec in type 2 diabetes: A meta‐analysis of ONWARDS phase 3 randomized controlled trials

Abstract

AimInsulin icodec is a novel ultra‐long action basal insulin analogue designed for once‐weekly administration. With the merit of once‐a‐week administration, it promises better adherence and greater treatment satisfaction because of reduced injection frequency. The purpose of this study was to ascertain the efficacy and safety of once‐weekly insulin icodec in comparison with other basal insulin analogues in the management of type 2 diabetes.Materials and MethodsThe PRISMA guidelines were followed during the conduct of this study. For the eligible studies, five databases and ClinicalTrials.gov were screened until July 2023. All randomized controlled trials comparing the efficacy and safety of insulin icodec in type 2 diabetes versus other insulin analogues were included. The extracted data were then analysed for meta‐analysis using RevMan 5.3 software.ResultsFive clinical trials with 3764 participants were included. The meta‐analysis showed that once‐weekly insulin icodec had higher glycated haemoglobin (HbA1c) reduction [mean difference −0.17%, 95% confidence interval (CI; −0.28 to −0.06), p = .003], with no significant difference in fasting plasma glucose compared with other insulin analogues. HbA1c achievement <7% [odds ratio 1.51, 95% CI (1.14‐1.99), p = .004] and HbA1c achievement <7% without hypoglycaemia [odds ratio 1.45, 95% CI (1.26‐1.67), p < .00001] were observed in higher proportions with insulin icodec compared with the comparator group. The percentage of time spent in the target glycaemic range was comparatively similar between insulin icodec and the comparator [mean difference 2.42%, 95% CI (0.01‐4.84), p = .05]. There was a significantly higher incidence of level 1 hypoglycaemia with insulin icodec but no significant difference was seen for the incidence of levels 2, 3 and combined 2/3 hypoglycaemia. Any adverse events and adverse events related to basal insulin were comparably similar in insulin icodec and comparators. The subgroup analysis of once‐weekly insulin icodec with individual insulin analogues (glargine U100 and degludec) showed that insulin icodec had similar efficacy with insulin glargine U100 but superior efficacy with higher HbA1c reduction with insulin icodec compared with insulin degludec. The safety profile was comparable between insulin icodec and glargine U100, whereas insulin icodec reported higher incidence of hypoglycaemia events and any adverse events when compared with degludec.ConclusionOnce‐weekly insulin icodec showed a better HbA1c reduction with a higher proportion of patients achieving HbA1c targets in comparison with once‐daily basal insulin analogues. They were no major safety concerns with respect to hypoglycaemia or adverse events.

Efficacy and safety of once-weekly insulin icodec compared to once-daily insulin g U-100 in patients with type II diabetes: a systematic review and meta-analysis

“…Furthermore, the estimated mean alteration in HbA1c (%) from baseline was found to be similar between the two groups, which is a new finding as previous meta-analyses have found a significant improvement in glycated hemoglobin percentage with Insulin Icodec [ 11 ]. Notably, the odds ratio for patients achieving HbA1c < 7% did not exhibit a significant difference between the two treatments in our analysis, contrary to the findings of Shetty, Sahana, and Renuka Suvarna, which demonstrated that once-weekly insulin icodec achieved superior glycated hemoglobin reduction and a higher proportion of patients reaching HbA1c targets (< 7%) compared to daily basal insulin analogues [ 27 ]. The significantly higher efficacy of once-weekly insulin icodec compared to once- daily Insulin Glargine U-100 that it may be a preferred option for achieving excellent glycemic control in patients with type 2 diabetes.…”

“…Even though, our analysis represents a slightly lesser TIR (%) difference between the two drugs after the addition of the latest trial with a larger sample size, it may still show a better glycemic control with Insulin Icodec compared to Glargine U-100. Other efficacy outcomes such as the estimated mean change in HbA1c (%) and FPG (mg/dL) did not show significant differences between Insulin Icodec and Insulin Glargine U-100, consistent with the finding of previous meta-analyses by Ribeiro E Silva, Rodrigo et al, Abuelazm, Mohamed et al, and Shetty, Sahana, and Renuka Suvarna, all of which demonstrated decreased HbA1c, increased TIR, and similar hypoglycemic events [ 11 , 26 , 27 ]. Furthermore, the estimated mean alteration in HbA1c (%) from baseline was found to be similar between the two groups, which is a new finding as previous meta-analyses have found a significant improvement in glycated hemoglobin percentage with Insulin Icodec [ 11 ].…”