Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence from the SURMOUNT-1 trial demonstrates that tirzepatide significantly reduces body weight compared to placebo, with a mean percentage change of -20.1% and a high percentage of patients achieving at least 5% weight loss (96.3% vs. 27.9% for placebo). This indicates a clear clinical advantage over standard care, although the long-term effects beyond 72 weeks remain uncertain.
Cost effectiveness
The ICER for tirzepatide in the target population is above the acceptable threshold of £20,000 per QALY gained, with estimates around £28,697 to £29,810. This indicates low cost-effectiveness, necessitating further justification for its price relative to the benefits provided.
Quality of life
While specific HRQoL data is not extensively detailed, the evidence suggests that tirzepatide improves quality of life through significant weight loss, which is likely to enhance daily functioning and well-being. However, the evidence is primarily based on weight loss outcomes rather than direct HRQoL measures.
Supporting Domains
Safety and Adverse Effects
Tirzepatide has a favorable safety profile, with most adverse events being mild to moderate. The trial data indicate that serious adverse events are rare, supporting a very good tolerability compared to existing therapies.
Comparator Selection
The comparators used in the trials, including semaglutide and diet/exercise support, are appropriate and reflect current treatment standards for obesity management. The evidence supports the relevance of these comparators in assessing tirzepatide’s effectiveness.
Patient Population and Subgroups
The trial population is broadly representative of the intended patient population, including those with relevant comorbidities. However, the exclusion of individuals with type 2 diabetes raises some concerns about generalizability.
Care Pathway Integration
Integrating tirzepatide into existing care pathways will require significant adjustments, particularly in ensuring adequate diet and exercise support, which may not be uniformly available across primary care settings.
Resource Use and Cost Implications
The anticipated budget impact of tirzepatide is significant, with estimates exceeding £20 million in the first three years. This raises concerns about the sustainability of its implementation within the NHS.
Evidence Quality and Robustness
The evidence base is strong, supported by a well-conducted Phase 3 trial (SURMOUNT-1) with a large sample size and robust methodology. However, some uncertainties remain regarding long-term outcomes.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the long-term effectiveness of tirzepatide and its broader impacts on health outcomes, particularly in populations excluded from the trials. This uncertainty may affect decision-making.
