Over the last century, significant advances have been made in the development of insulin formulations, including very rapid and prolonged-release analogs of basal insulin. Insulin icodec, a novel basal insulin analog with a one-week half-life that only needs to be administered once weekly, offers potential benefits by increasing convenience, adherence and quality of life for better glycemic control.
It is expected that 6.28% (462 million) of the world’s population will have type 2 diabetes (T2D) in the next 30 years and that more than 1.3 billion people worldwide will be affected. Despite the availability of various treatment options, achieving adequate glycemic control remains a challenge for many patients due to several factors, including lack of adherence, fear of injections, hypoglycemia, weight gain and cost of treatment. Once-daily basal insulin analogs have partially addressed these issues, but research shows that patients would welcome a further reduction in dosing frequency to once weekly.
A group of researchers led by Syed Zia Saleem from the Department of Medicine at Dow University of Health Sciences in Karachi, Pakistan, conducted a systematic review and meta-analysis to evaluate the efficacy and safety of once-weekly insulin icodec compared with once-daily insulin glargine U-100 in people with T2D [1]. Previous meta-analyses have compared this novel weekly insulin regimen with either once-daily insulin glargine U-100 or degludec, finding similar glycemic efficacy combined with better or similar safety profiles. However, more research has been published since then, so Saleem and colleagues analyzed the comparison in light of the latest findings with a larger sample.
The scientists considered data from four studies for their review. In total, an adult patient population of 1035 (age 18-72 years, BMI 18.5-37.9 kg/m2, HbA1c ≤75 mmol/mol [≤9.0%]) with T2D was included. All studies were double-blind and had a parallel group design, three were open-label. The studies included both insulin-inexperienced participants and those already treated with basal insulin for T2D.
The primary endpoint was the estimated mean change from baseline in TiR (%) and HbA1c (%), focusing on the estimated mean percentage change from baseline and the incidence of hypoglycemia, both in alert and clinically significant and severe cases. Other assessments included shifts in the estimated mean reduction in fasting plasma glucose (FPG, mg/dl), changes in body weight (kg) from baseline, the proportion of participants achieving HbA1c levels of less than 7%, and monitoring of all adverse events as well as those likely or possibly related to basal insulin, injection site reactions and hypersensitivity reactions.
Facilitated insulin management possible
The pooled mean difference (MD) showed a 4.68% longer TiR with insulin icodec vs. insulin glargine U-100 (95% CI 0.69–8.68; p=0.02), the estimated mean changes in HbA1c and FPG were found to be non-significant between the two groups. The overall OR for hypoglycemia was also non-significant between the two therapies at 1.04 (95% CI 0.71–1.52; p=0.84). Other safety parameters were similar in both groups. According to international consensus, every 5 percent increase in TiR is considered a clinically significant improvement in glycemic control, the authors emphasize. The fact that the change in HbA1c vs. baseline was similar in both groups is also a new finding, as previous meta-analyses had found a significant improvement in the percentage of glycated hemoglobin with insulin icodec.
Basal insulin in type 2 diabetes is usually recommended when non-insulin therapies prove inadequate to achieve glycemic targets. These barriers may include delays in initiating or adjusting insulin therapy, needle phobia leading to failure to take daily injections, instances of missed insulin doses, discontinuation of insulin, and the occurrence of hypoglycemia. A systematic review by Singh et al. has highlighted insulin icodec as the most advanced insulin candidate suitable for once-weekly administration [2]. It shows the potential to reduce injection frequency by over 85% compared to once-daily basal insulin analogs and offers a similar benefit to once-weekly vs. once-daily glucagon-like peptide-1 (GLP1) receptor agonists.
The authors also point out that the odds ratio for patients achieving HbA1c <7% did not show a significant difference between the two treatments in their analysis, in contrast to the results of previous studies showing that once-weekly insulin icodec achieved better glycosylated hemoglobin lowering and a higher proportion of patients achieving HbA1c targets <7% compared to daily basal insulin analogs. The significantly higher efficacy of once-weekly insulin icodec compared to once-daily insulin glargine U-100 may make it a preferred option for excellent glycemic control in patients with type 2 diabetes.
No significant changes in body weight
In terms of safety outcomes, including estimated mean body weight change, overall hypoglycemia, adverse events related to insulin, hypersensitivity and injection site reactions, there were no significant differences in risk between the two insulin therapies. These results suggest that once-weekly administration of insulin icodec may provide a convenient alternative to conventional daily injections without compromising glycemic control. This conclusion is consistent with the results of previous network meta-analyses. In addition, the lack of significant differences in hypoglycemic episodes, both hypoglycemic alerts and severe hypoglycemia, was reassuring. The non-significant changes in body weight between the two insulin therapies were also an additional advantage. However, this is in contrast to the findings of Abuelazm et al. in which once-weekly insulin icodec was associated with an increase in body weight [3].
However, Saleem et al. point out that an important limitation of their analysis is the small number of included studies, which led to a relatively small total group of participants. This could affect the reliability of the results. Another problem was the varying duration of the included studies, which could make it difficult to draw consistent conclusions. Therefore, more long-term studies with larger samples should be conducted for more clarity. Finally, in one of the four studies included in the review, all participants were already on basal insulin therapy, which may have affected the overall results, as insulin-resistant patients generally have difficulty adjusting to weekly dosing and are prone to hypoglycemic episodes, unlike patients already using basal insulin.
Literature:
- Saleem SZ, et al: 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. Diabetol Metab Syndr 2024; 16: 80; doi: 10.1186/s13098-024-01305-z.
- Singh AK, et al: Once-weekly basal insulin icodec: looking ONWARDS from pharmacology to clinical trials. Diabetes Metab Syndr 2022; 16(9): 102615.
- Abuelazm M, et al: Once-weekly insulin icodec versus once-daily long-acting insulin for type II diabetes: a meta-analysis of randomized controlled trials. J Endocr Soc 2023; 8(2): 177.
InFo DIABETOLOGIE & ENDOKRINOLOGIE 2024; 1(4): 39–40
