Once-Weekly Insulin Icodec vs. Once-Daily Insulin Glargine U100 for type 2 diabetes: a systematic review and meta-analysis of phase 2 randomized controlled trials

Abstract

Objective: Insulin Icodec is a novel basal insulin analogue designed for once-weekly administration, therefore might propitiate reduction in the frequency of injections and facilitate treatment adherence. This study aimed to determine the glycemic control and safety profile of Insulin Icodec, compared with Glargine U100 in patients with diabetes mellitus type 2. Materials and methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCT) data comparing Once-Weekly Insulin Icodec and Once-Daily Insulin Glargine U100 in patients with type 2 diabetes mellitus. PubMed, Embase, and Cochrane databases were searched for trials published up to May 14, 2022. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Results: Three studies were included comprising 453 patients, 230 (50.77%) using Once-Weekly Insulin Icodec and 223 (49.22%) using Once-Daily Insulin Glargine U100. In the pooled data, Glycated Hemoglobin (MD -0.20% CI -0.33 to -0.07%; P=0.002) change from baseline demonstrated a significantly higher reduction in the Icodec group. Time with Glucose in Range (MD 6.60% CI 3.63 to 9.57%; P < 0.0001) and Insulin Dose Difference (MD 0.97UI CI 0.76 to 1.18UI; P < 0.0001) were higher in the Icodec group. There was no significant difference in fasting plasma glucose, body weight change, hypoglycemia or any adverse event evaluated. Conclusions: Once-Weekly Insulin Icodec was associated with a small reduction in Glycated Hemoglobin, as well as higher Time with Glucose in Range, with similar hypoglycemic adverse events, when compared with Once-Daily Insulin Glargine U100. KeywordsType 2 diabetes mellitus; insulin; insulin long-acting; insulin glargine; insulin icodec; glycemic control; glycated hemoglobin A Insulin Icodec vs. Glargine for type 2 diabetes: a systematic review and meta-meta-analysis

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

“…In this meta‐analysis, once‐weekly insulin icodec showed superiority with a higher HbA1c reduction in comparison with once‐daily basal insulin analogues. This result is similar to the meta‐analysis of phase 2 studies of once‐weekly insulin icodec ( p = .002) 18 . There was no significant difference with respect to the FPG between insulin icodec and the comparators, which is in par with previous phase 2 meta‐analysis 18 .…”

“…The TIR (70‐180 mg/dl) and TBR <70 mg/dl was comparably similar with once‐weekly insulin icodec and comparators; however, TBR (<54 mg/dl) was higher in insulin icodec and TAR (>180 mg/dl) was higher for the comparator group. There was significantly great weight reduction with insulin icodec as compared with the comparators in this meta‐analysis, which was not similar when compared with the meta‐analysis of phase 2 18 . In addition, the total insulin dose ratio in the insulin icodec group was higher when compared with other insulin analogues.…”

“…With respect to the incidence of hypoglycaemia, there was a higher incidence of level 1 hypoglycaemia with insulin icodec compared with the comparators, whereas there was no significant difference in clinically significant hypoglycaemia (level 2), severe hypoglycaemia (level 3) and combined (level 2/3) hypoglycaemia with once‐weekly insulin icodec in comparison with the once‐daily basal insulin analogues. The adverse events profile between insulin icodec and comparators was comparably similar with no statistically significant differences, akin to the adverse effect profile in phase 2 meta‐analysis 18 . There was no significant difference with respect to the rate of hypoglycaemia per patient‐year for level 1, level 2, level 3 and combined level 2/3 hypoglycaemia.…”

Efficacy and safety of once-weekly basal insulin versus once-daily basal insulin in patients with type 2 diabetes: A systematic review and meta-analysis

“…However, this meta-analysis included only 453 patients. [22] Our meta-analysis included the recently updated Phase 2 and III clinical trials involving a total of 2391 patients, and conducted a subgroup analysis to explore the impact of prior insulin-treated, insulin type, and treatment duration on the outcome. Therefore, our results are more reliable and instructive.…”

Clinical Outcomes With Once‐Weekly Insulin Icodec Versus Once‐Daily Insulin Glargine U100 in Insulin‐Naïve and Previously Insulin‐Treated Individuals With Type 2 Diabetes: A Meta‐Analysis of Randomised Controlled Trials

“…According to pharmacokinetic and pharmacodynamic studies, the glucose‐lowering impact of insulin icodec is uniformly distributed throughout a 1‐week dose interval [ 9 ]. Although a prior meta‐analysis was performed to compare the weekly use of insulin icodec with the daily use of insulin glargine regarding safety and effectiveness [ 10 ], its limited sample size and the inclusion of only Phase 2 trials make it impractical to establish any firm conclusions. To address this literature gap and to assist with improved decision‐making when choosing between weekly use of insulin icodec and daily use of insulin glargine, we conducted systematic review and meta‐analysis with a considerably larger sample size by including recently published phase 3 trials.…”