UK Public Agency Won't Recommend Weight Loss Drug Mounjaro, Needs More Evidence

UK Public Agency Won't Recommend Weight Loss Drug Mounjaro, Needs More Evidence
Tirzepatide medication for Type 2 diabetes 3D rendering. (Shutterstock)
Harry Lee

UK's health and social care watchdog has decided against recommending Mounjaro, Eli Lilly's weight loss drug for adults with diabetes.

The National Institute for Health and Care Excellence (NICE) in the UK released draft guidance stating that they need more information about tirzepatide, the active ingredient in Mounjaro.

“Our committee can see the promise in tirzepatide, but it requires more evidence to be able to evaluate both its clinical and cost-effectiveness,” said Helen Knight, director of medicines evaluation at NICE.

NICE provides national guidance and evaluates the cost-effectiveness of medications. As a nondepartmental public body, it operates under the sponsorship of the Department of Health and Social Care.

Why the Need for More Evidence?

The draft guidance (pdf) brought attention to the "uncertainties in the clinical evidence" provided by the manufacturer.

According to the clinical trials, tirzepatide demonstrated potential in reducing blood glucose levels and body weight when compared to semaglutide, insulin therapy, or a placebo. The company's network meta-analysis also indicated similar effects compared to all glucagon-like peptide 1 (GLP-1) receptor agonists. However, the draft said, there were uncertainties surrounding these results.

Furthermore, the draft guidance highlighted uncertainties regarding the cost-effectiveness estimates. It remained unclear how accurately the model predicted the long-term health benefits of tirzepatide compared to other GLP-1 receptor agonists (Wegovy and Ozempic) and how the company's model results aligned with other economic models for diabetes.

“Lilly is disappointed that NICE’s draft guidance does not currently recommend tirzepatide for Type 2 diabetes,” Brooke Frost, a spokesperson for Eli Lilly, told The Epoch Times via email. “Lilly’s submission to NICE was based on a new cost-effectiveness model, which has raised several technical questions from the committee. We will continue to work closely with NICE to provide further technical clarification on the model during the consultation period." There is a meeting with the Appraisal Committee scheduled for August. The final draft guidance is expected in September.

While Mounjaro has not received approval in the UK, it obtained marketing authorization in September 2022, which means the drug can now be legally marketed within the UK. The U.S. Food and Drug Administration (FDA) approved Mounjaro for treating Type 2 diabetes patients in May 2022.

The Epoch Times has contacted the FDA for comments.

Several Drugs Show Promise in Obesity Treatment

The weight loss and weight management market has reached over $200 billion globally. Numerous companies are actively developing drugs and vying for their portion of this lucrative market.

A phase 3 clinical trial, funded by Eli Lilly and recently published in The Lancet, showcased the efficacy of tirzepatide in reducing average body weight by about 15 percent at the highest dose (15 milligrams) in adults with obesity or overweight and Type 2 diabetes. The study also highlighted significant improvements in blood sugar levels among participants treated with tirzepatide.

Tirzepatide was anticipated to position Eli Lilly as a leading player in the therapy for obesity and Type 2 diabetes, surpassing drugs like Ozempic and Wegovy.

Eli Lilly has completed its submission for chronic weight management and is awaiting potential FDA approval, which is expected later in 2023.

The New England Journal of Medicine (NEJM) published two phase 2 clinical trials on June 23 and June 26, both funded by Eli Lilly.

The first study demonstrated the potential of orforglipron, a daily oral GLP-1 receptor agonist, to help with weight loss. Up to 75 percent of participants who received orforglipron achieved a weight reduction of at least 10 percent by week 36, compared to only 9 percent in the placebo group.
The second study showcased the substantial reduction in body weight achieved—up to 17.5 percent after 24 weeks or 24.2 percent after 48 weeks.
Tirzepatide mimics two hormones, glucose-dependent insulinotropic polypeptide (GIP) and GLP-1, to suppress appetite, while Ozempic and Wegovy, popular drugs by Novo Nordisk, solely target GLP-1 with the active substance semaglutide.

An Increasing Number of Safety Concerns

While most clinical trials of GLP-1-related hormone receptor agonists claimed low discontinuation rates and gastrointestinal side effects, recent safety concerns have surfaced.
In April, the European Medicines Agency issued a drug safety signal (pdf) regarding a potential risk of thyroid cancer associated with certain classes of medications that include semaglutide. The agency required drug manufacturers, such as Novo Nordisk, AstraZeneca, Eli Lilly, and Sanofi Winthrop, to submit supplementary information by July 26, 2023.
Health Canada, responsible for Canada's national health policy, issued a warning this month stating that using Ozempic for weight loss "is not an approved indication" and may lead to "serious side effects," including pancreatitis, severe hypoglycemia, gallbladder issues, severe allergic reactions, thyroid tumors, and kidney problems, including kidney failure.

On June 26, Pfizer announced that the clinical development of lotiglipron would be halted due to an increase in liver enzyme levels. Pfizer said that no liver failure or liver-related side effects were reported and that it would continue to advance danuglipron for treating obesity and Type 2 diabetes.

Both lotiglipron and danuglipron are GLP-1 agonists, with the distinction that danuglipron is taken orally twice daily, while lotiglipron is taken orally once daily.

Some doctors have raised concerns regarding the working mechanisms of these drugs, in addition to concerns about side effects. Since they primarily suppress appetite rather than promote fat burning, there is a potential risk of muscle loss, leading to additional health problems.

A 2022 study found that individuals who stopped taking semaglutide regained two-thirds of the lost weight within one year. Furthermore, improvements in cardiometabolic complications, such as Type 2 diabetes and high blood pressure, were reversed.