The National Institute for Health and Clinical Excellence (NICE) has recommended tirzepatide (Mounjaro, Eli Lilly) as a new treatment option for some people in England with type 2 diabetes (T2D) for whom existing management options are insufficient.
In final draft guidance, NICE explained that patients for whom triple therapy with metformin and two other oral antidiabetic drugs was ineffective, not tolerated or contraindicated, currently had limited treatment options. They had the choice of switching one of the antidiabetic drugs for a glucagon-like peptide-1 (GLP-1) receptor agonist, such as semaglutide (Wegovy, Novo Nordisk), or starting insulin therapy.
There was a high unmet need for new treatment options, as at least one in three T2D patients did not maintain HbA1c levels below the recommended 53 mmol/mol (7%).
Eli Lilly had asked for the drug to be considered only as an alternative to GLP-1 receptor agonists inadequately controlled with three or more antidiabetic drugs. This was despite having marketing authorisation as monotherapy when metformin is considered inappropriate due to intolerance or contraindications, and even though internationally, tirzepatide is used earlier in the treatment pathway.
The rationale was that the company anticipated that when tirzepatide was used in NHS practice, it would be prescribed along with two oral agents, because GLP-1 receptor agonists when used in the NHS were limited to third or fourth line drugs. Like semaglutide, approved by NICE earlier this year for NHS use to aid weight loss, and used within specialist weight management services in patients with comorbidities including diabetes, tirzepatide must be given by weekly injection – so these drugs were less easily adopted in primary care than oral tablets.
Significantly Better HbA1c Reductions Than Comparator Drugs
NICE noted that clinical trial results had suggested that tirzepatide reduced HbA1c levels and body weight compared with semaglutide, insulin therapy, or placebo, with similar benefits on indirect comparisons with other GLP-1 receptor agonists. Across all trials presented in evidence, 81% to 97% of people reached HbA1c levels of less than 53 mmol/mol (7%), which was significantly more than with any comparator. Some trials had also shown better weight reductions.
The company had provided additional analyses that had "improved confidence in the clinical- and cost-effectiveness evidence" such that cost-effectiveness estimates were within the range that NICE considered an acceptable use of NHS resources.
NICE said that tirzepatide could be used for treating T2D alongside diet and exercise in adults when the condition was insufficiently controlled only if:
- Triple therapy with metformin and 2 other oral antidiabetic drugs is ineffective, not tolerated or contraindicated, and
- Patients have a body mass index (BMI) of 35 kg/m2 or more, and specific psychological or other medical problems associated with obesity, or
- They have a BMI of less than 35 kg/m2, and:
- insulin therapy would have significant occupational implications, or
- weight loss would benefit other significant obesity-related complications
Doctors were advised to use lower BMI thresholds (usually reduced by 2.5 kg/m2) for people from South Asian, Chinese, other Asian, Middle Eastern, Black African or African-Caribbean family backgrounds.
Unusually, the committee said it would have "preferred to have assessed tirzepatide in the broader population aligned with the NICE scope". But the company's positioning within a narrower patient population meant it was "not presented with any evidence" to enable it to do so. Accordingly, tirzepatide was recommended "in a narrower population than its marketing authorisation".
Another Effective Treatment Option for T2D
Asked to comment by Medscape News UK, Douglas Twenefour, head of care at Diabetes UK, said: "We welcome NICE's decision to approve tirzepatide to be prescribed on the NHS, as this will provide another effective treatment option for managing type 2 diabetes." He said it was "very promising" that trial data showed great improvements in both blood glucose management and weight loss.
However, he cautioned that the current GLP-1 medication shortages — due to the popularity of these drugs as weight loss agents — were "causing stress and uncertainty" for many patients. "Whilst the approval of tirzepatide is welcome, we are calling for more action to ensure ongoing and sufficient supply of these medications to people with T2D."
NICE has a separate appraisal underway on tirzepatide for weight loss, with guidance expected to be published next March.
Final guidance on tirzepatide for diabetes is due to be published on 11 October, meaning that the drug should be available early next year. Around 180,000 people with "difficult to manage T2D" could benefit, NICE said.
The proposed list price of four prefilled disposable injections — representing four weeks' supply — is commercial in confidence until the guidance is published.