Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence from the SURPASS trials indicates that tirzepatide significantly reduces HbA1c levels and body weight compared to semaglutide and insulin therapy. The trials were phase 3 studies, which provide robust evidence of clinical effectiveness. The results showed that 81% to 97% of participants achieved HbA1c levels below 53 mmol/mol (7%), which is a substantial improvement over existing therapies.
Cost effectiveness
The cost-effectiveness estimates for tirzepatide were reported to be less than £20,000 per QALY gained against all comparators, which is within NICE’s acceptable range. The additional analyses provided after consultation improved confidence in the economic model, supporting its cost-effective use in the NHS.
Quality of life
While specific HRQoL data was not extensively detailed, the evidence suggests that tirzepatide leads to weight loss and improved glycemic control, which are likely to enhance overall well-being. The committee noted that the adverse effects were manageable, indicating a positive impact on HRQoL.
Supporting Domains
Safety and Adverse Effects
Tirzepatide was generally well tolerated in the SURPASS trials, with common adverse effects being nausea and vomiting, which are consistent with other GLP-1 receptor agonists. The clinical experts indicated that these adverse effects are manageable, suggesting an acceptable safety profile.
Comparator Selection
The company appropriately selected GLP-1 receptor agonists as comparators, which are relevant to the positioning of tirzepatide in the treatment pathway. The committee agreed that the chosen comparators represented those used in NHS practice, ensuring the relevance of the evidence.
Patient Population and Subgroups
The trial populations in the SURPASS studies were generally representative of the intended NHS population, with a focus on individuals with type 2 diabetes inadequately controlled on multiple oral antidiabetic drugs. However, there were some limitations in subgroup analyses.
Care Pathway Integration
Tirzepatide can be integrated into existing care pathways with some adjustments, particularly in terms of administration and monitoring. The committee noted that while it may require some changes, these are manageable within current clinical practice.
Resource Use and Cost Implications
The budget impact of tirzepatide is considered manageable, with the potential for cost savings due to improved glycemic control and reduced complications associated with type 2 diabetes. The commercial arrangement further supports its economic viability.
Evidence Quality and Robustness
The evidence base is supported by multiple phase 3 RCTs (SURPASS trials) with low risk of bias. The additional analyses provided after consultation enhanced the robustness of the evidence, making it credible for decision-making.
Uncertainty, Sensitivity, and Broader Impacts
While there are some uncertainties related to the NMA and the generalizability of results, the committee noted that the additional analyses helped mitigate these concerns. The societal context and unmet need for effective diabetes treatments further support the use of tirzepatide.
