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

Abstract

Background//objective: Diabetes affects millions of people globally, despite treatment options, adherence and other factors pose obstacles. Once-weekly Insulin Icodec, a novel basal Insulin analog with a week-long half-life, offers potential benefits, enhancing convenience, adherence, and quality of life for improved glycemic control. This systematic review and meta-analysis aimed to assess the efficacy and safety of once-weekly Insulin Icodec compared to once-daily Insulin Glargine U-100 in individuals with type II diabetes (T2D).

Methods: A comprehensive literature search was conducted using PubMed, and Cochrane Library databases before September 2023 to identify relevant Randomized control trials (RCTs) with no language restrictions following PRISMA guidelines. The Cochrane risk-of-bias tool was used for quality assessment. All statistical analyses were conducted using RevMan (version 5.4; Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).

Result: Four RCTs published from 2020 to 2023 with a cumulative sample size of 1035 were included. The pooled mean difference (MD) revealed a 4.68% longer TIR (%) with Insulin Icodec compared to Insulin Glargine U-100 [{95% CI (0.69, 8.68), p = 0.02}], the estimated mean changes in HbA1c (%) and FPG (mg%) were found to be insignificant between the two groups [MD = - 0.12 {95% CI (- 0.26, 0.01), p = 0.07}] and [MD = - 2.59 {95% CI (- 6.95, 1.78), p = 0.25}], respectively. The overall OR for hypoglycemia was also nonsignificant between the two regimens 1.04 [{95% CI (0.71, 1.52), p = 0.84}]. Other safety parameters were similar between the two groups.

Conclusions: Switching from daily Insulin Glargine U-100 to weekly Insulin Icodec showed longer TIR (%) as well as similar blood glycemic control and safety profile. Hence, it may be a good alternate option for management of longstanding T2D.

Keywords: Glycemic control; Insulin Glargine U-100; Insulin Icodec; Once-weekly Insulin regimen; Type 2 diabetes (T2D).

Fig. 1

PRISMA Flow Diagram of the Literature Search Process

Fig. 2

Risk of bias summary. The Cochrane “risk of bias” tool was used for quality assessment. Green for “no risk” and yellow for “unclear risk”

Fig. 3

Forest plot of comparison: 1 Once weekly Insulin Icodec vs Once daily Insulin Glargine U-100, outcome: 1.1 Estimated Mean Change in Time with glucose in range (%) from baseline. Pooled analysis has been shown based on both common and random effects model

Fig. 4

Forest plot of comparison: 1 Once weekly Insulin Icodec vs Once daily Insulin Glargine U-100, outcome: 1.2 Estimated Mean Change in HbA1c (%) from baseline. Pooled analysis has been shown based on both common and random effects model

Fig. 5

Forest plot of comparison: 1 Once weekly Insulin Icodec vs Once daily Insulin Glargine U-100, outcome: 1.3 Estimated Mean Change in Fasting Plasma Glucose (md/dL) from baseline

Fig. 6

Forest plot of comparison: 1 Once weekly Insulin Icodec vs Once daily Insulin Glargine U-100, outcome: 1.4 Odds ratio of participants achieving HbA1c < 7%

Fig. 7

Forest plot of comparison: 1 Once weekly Insulin Icodec vs Once daily Insulin Glargine U-100, outcome: 1.5 Odds ratio for Any Adverse Event

Fig. 8

Forest plot of comparison: 1 Once weekly Insulin Icodec vs Once daily Insulin Glargine U-100, outcome: 1.6 Odds ratio of Overall Hypoglycemia. Subgroup analysis was performed based on the severity of hypoglycemia I.e., Hypoglycemia alert and combined clinically significant or severe hypoglycemia

Fig. 9

Forest plot of comparison: 1 Once weekly Insulin Icodec vs Once daily Insulin Glargine U-100, outcome: 1.7 Estimated Mean Change in Body weight (kg) from baseline

Fig. 10

Forest plot of comparison: 1 Once weekly Insulin Icodec vs Once daily Insulin Glargine U-100, outcome: 1.8 Odds ratio for Injection site reactions

Fig. 11

Forest plot of comparison: 1 Once weekly Insulin Icodec vs Once daily Insulin Glargine U-100, outcome: 1.9 Odds ratio for Hypersensitivity reactions

Fig. 12

Forest plot of comparison: 1 Once weekly Insulin Icodec vs Once daily Insulin Glargine U-100, outcome: 1.10 Odds ratio for Adverse events probably/possibly due to basal insulin