insulin efsitora alfa for treating type 2 diabetes

Insulin efsitora alfa is a novel once-weekly basal insulin fusion protein consisting of a single-chain insulin analogue linked to a human IgG2 Fc domain, extending its circulating half-life to 15–16 days (1,2).

A systematic review and meta-analysis found (1):

• demonstrates non-inferiority to daily basal insulins in HbA1c reduction (mean difference -0.04%, p = 0.15), fasting plasma glucose, and proportion of patients achieving HbA1c < 7% (OR 1.10, p = 0.32)
• continuous glucose monitoring (CGM) metrics:
  • time in range (TIR 3.9-10.0 mmol/L): statistically significant increase compared to daily insulin (mean difference +0.80 percentage points, p = 0.03)
  • time above range (TAR > 10.0 mmol/L): statistically significant reduction (mean difference -1.45 percentage points, p = 0.05)
  • time below range (TBR < 3.9 mmol/L): no significant difference compared to daily basal insulins (p = 0.62)
• weight impact: body weight changes are comparable to once-daily basal insulins (mean difference 0.12 kg, p = 0.47)
• safety and adverse events:
  • overall treatment-emergent adverse events (TEAEs) were higher with efsitora (RR 1.12, p = 0.001), driven primarily by mild/moderate non-serious events
  • no significant differences observed in serious adverse events (SAEs), injection site reactions, hypersensitivity, or overall/severe hypoglycaemia rates

NICE state (2):

• insulin efsitora alfa can be used, within its marketing authorisation, as an option to treat type 2 diabetes in adults
• use the least expensive option of the suitable treatments (including insulin efsitora alfa and basal insulin intended for administration once or twice a day), having discussed the advantages and disadvantages of the available treatments with the person with the condition
  • take account of administration costs, dosages, price per dose and commercial arrangements

The NICE committee noted that (2):

• “..Clinical trial evidence shows that insulin efsitora alfa is as effective at controlling blood glucose levels as 2 other basal insulins (insulin degludec and insulin glargine) both at the 100-unit concentration level, over 26 to 52 weeks. But the people who would benefit most from once-weekly insulin are underrepresented in the trials. This adds to the uncertainty about the treatment effect, but including these people in the trials would be difficult. Overall, the evidence can be applied to people having treatment in the NHS…”
• “..The biggest cost saving from using insulin efsitora alfa comes from people needing less support to take their insulin. This is because insulin efsitora alfa is taken once a week rather than every day. An average of 1 hour with a specialist district nurse for diabetes is assumed each time a person needs help taking insulin. But the amount of help a person needs may vary. The impact of this has not been fully explored in different scenarios, which adds uncertainty to the results…”
• “..A cost comparison suggests that overall costs for insulin efsitora alfa are similar to or lower than overall costs for basal insulin intended for administration once or twice a day, assuming that:
  • the health benefits of insulin efsitora alfa are similar to other basal insulins, and
  • some people need help to take their insulin…So, insulin efsitora alfa can be used…”

Reference:

1. Mehmood H et al. Once-Weekly Insulin Efsitora Alfa Versus Once Daily Insulin in Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis. Endocrinology, Diabetes & Metabolism. 2025;8:e70126.
2. National Institute for Health and Care Excellence (NICE). Insulin efsitora alfa for treating type 2 diabetes. Technology appraisal guidance [TA1200]. Published October 16, 2026.