Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Tirzepatide demonstrated a clear clinical advantage over comparators, showing statistically significant reductions in HbA1c levels and body weight across multiple Phase 3 trials (SURPASS-2 to -5). The evidence indicates that 81% to 97% of participants achieved HbA1c levels below 53 mmol/mol (7%), which is a significant improvement compared to existing therapies. However, the reliance on indirect comparisons with other GLP-1 receptor agonists introduces some uncertainty.
Cost effectiveness
The cost-effectiveness estimates for tirzepatide are reported to be less than £20,000 per QALY gained against all comparators, which is within NICE’s acceptable range. Additional analyses provided by the company improved confidence in the economic model, supporting its cost-effective use in the Healthcare.
Quality of life
While the document does not provide extensive HRQoL data, the significant weight loss and improved glycemic control associated with tirzepatide are likely to contribute positively to patients’ overall well-being. The committee acknowledged that the adverse effects are manageable, which supports the potential for moderate improvements in HRQoL.
Supporting Domains
Safety and Adverse Effects
Tirzepatide was generally well tolerated in clinical trials, with common adverse effects being nausea, dyspepsia, and vomiting. These are consistent with other GLP-1 receptor agonists and are considered manageable in clinical practice. The committee noted that the adverse effects are not severe enough to undermine the overall benefit of the treatment.
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 reflect those used in Healthcare practice, although there was some concern about the exclusion of certain treatments.
Patient Population and Subgroups
The trial populations in the SURPASS studies were generally representative of the intended patient population in the Healthcare, with a focus on those inadequately controlled on existing therapies. However, the committee noted that the Healthcare population may have more lines of previous treatment than those in the trials.
Care Pathway Integration
Tirzepatide can be integrated into existing care pathways with some adjustments, particularly regarding the titration of doses. The committee acknowledged that while there may be some challenges in adoption due to the injectable nature of the treatment, it is manageable within current practices.
Resource Use and Cost Implications
The budget impact of tirzepatide is considered manageable, with the potential for cost savings due to improved management of diabetes-related complications. The committee noted that the overall resource use aligns with the expected benefits of the treatment.
Evidence Quality and Robustness
The evidence base is supported by multiple Phase 3 RCTs with low bias risk, and additional analyses have strengthened the credibility of the findings. The committee found the evidence robust enough to support the recommendations, despite some limitations in the NMA.
Uncertainty, Sensitivity, and Broader Impacts
While there are some uncertainties related to the indirect comparisons and the NMA, the overall context of high unmet need for effective diabetes treatments mitigates these concerns. The committee felt that the potential benefits of tirzepatide justify its use despite these uncertainties.
