Before tirzepatide could be recommended for NHS use, more evidence was needed on its clinical and cost-effectiveness for people with type 2 diabetes, the National Institute for Health and Care Excellence (NICE) said.
Tirzepatide (Mounjaro, Eli Lilly), a weight loss jab injected weekly similar to Wegovy (which was recommended in February), works by helping a person feel full on less food, and by slowing the passage of food through the digestive tract. NICE highlighted that the drug was a first in class dual GLP-1 and GIP RA.
The regulator explained that the drug's manufacturer had "positioned" tirzepatide as an option later in the diabetes treatment pathway to offer the NHS an alternative to glucagon like peptide 1 (GLP-1) receptor agonists such as dulaglutide, liraglutide, and semaglutide (Ozempic, Rybelsus), which were already recommended for use in the NHS.
NICE recognised the importance of new treatment options, particularly given that fewer than two-thirds of adults with type 2 diabetes had adequate glucose control when using current treatment options.
Helen Knight, director of medicines evaluation, at NICE, said: "Type 2 diabetes is becoming more prevalent in society, so new treatment options are needed to help people with it to control their blood-glucose levels."
Clinical Evidence and Value for Money 'Uncertain'
In its draft guidance, NICE described how some people with type 2 diabetes had triple therapy with metformin and two other oral antidiabetic drugs. When this was "not effective, not tolerated, or contraindicated", a person might switch one of the antidiabetic drugs for a glucagon-like peptide-1 (GLP-1) receptor agonist or start insulin therapy, the authors said.
"For this evaluation, the company asked for tirzepatide to be considered only as an alternative to GLP-1 receptor agonists," a NICE spokesperson pointed out.
Clinical trials showed the use of tirzepatide at any dose resulted in better glucose control and lower weight compared with semaglutide or insulin therapy. "The weight reduction was more pronounced with higher doses of tirzepatide, while the effect on glucose levels seemed less dose-dependent," noted NICE, and added that similar effects were observed against all GLP-1 receptor agonists in the company's network meta-analysis, but that the results were "uncertain".
In addition to the uncertainties in the clinical evidence, NICE warned that there were "issues with the company’s economic model". These included that:
- The external assessment group was unable to fully scrutinise it
- It was unclear how accurately it predicted the long-term health outcomes with tirzepatide and GPL-1 receptor agonists
- There was no evidence showing how the model results compared with other economic models for diabetes
"So, it is yet to be established if tirzepatide represents good value for money, since the cost-effectiveness estimates are uncertain," NICE stressed.
The price of the pre-filled disposable injection pens was commercial in confidence until final guidance is published.
NICE: 'Promise' in Tirzepatide for Type 2 Diabetes
Eli Lilly needed to provide more data to address the uncertainties in the clinical evidence, when compared to all relevant alternative treatments, said a NICE spokesperson. This should be provided alongside "further analyses and clarifications" on the company's submitted economic model, NICE counselled.
Therefore, NICE confirmed that tirzepatide was "not recommended", within its marketing authorisation, for treating type 2 diabetes (T2D) alongside diet and exercise in adults when it is insufficiently controlled alone when metformin cannot be taken because of intolerance or contraindications, or with other antidiabetic drugs
The regulator reassured people having treatment outside this recommendation that they may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician considered it appropriate to stop.
Earlier this month Professor Sir Stephen O'Rahilly, professor of clinical biochemistry and medicine and director of the Medical Research Council Metabolic Diseases Unit at the University of Cambridge, commented on a New England Journal of Medicine study that investigated the role of tirzepatide in the treatment of obesity. He said that "treatment of people with obesity with a weekly injection of tirzepatide produced weight loss similar to that seen with weight loss surgery". He added that blood tests had shown “improvements in all the markers of metabolic and cardiovascular health".
Speaking to Medscape News UK , Dr Kevin Fernando, GP and Primary Care Diabetes Society Scottish lead, expressed disappointment at NICE's decision. He acknowledged the need for further health economic data but alerted that "we are facing an epidemic of younger individuals with significant cardiometabolic disease". The "compelling reductions" in weight and glycaemia with tirzepatide, as well as clinically meaningful improvements in cardiometabolic risk factors, "positions tirzepatide perfectly" as the first injectable of choice when treatment intensification was required, particularly for younger people living with type 2 diabetes and obesity, he claimed.
Ms Knight stressed that NICE could see "the promise" in tirzepatide, but that the regulator required more evidence to be able to evaluate both its clinical and cost effectiveness.
A consultation on the committee's decision has begun and comments can be submitted until Tuesday 18 July 2023.
Dr Fernando has written articles and commentaries for Medscape UK.