The US Food and Drug Administration has expanded the approved use of Mounjaro, Eli Lilly’s blockbuster diabetes drug, to include reducing the risk of major cardiovascular events in adults with type 2 diabetes who are at high risk.
The decision gives tirzepatide, better known by the brand name Mounjaro, an important new cardiovascular indication. But the underlying study comes with a significant nuance: Mounjaro proved that it was at least as effective at preventing major cardiovascular events as another established diabetes drug. It did not prove that it was better.
For patients in Israel, there is another important distinction. The FDA decision does not automatically change Mounjaro’s approved uses in Israel, where the drug is already available but remains outside the national health basket for adults.
What exactly did the FDA approve?
Eli Lilly announced on August 28 that the FDA had approved Mounjaro to lower the risk of major adverse cardiovascular events, including cardiovascular death, nonfatal heart attack and nonfatal stroke, in adults with type 2 diabetes who are at high risk for such events.
This is an expansion of Mounjaro’s existing approval, not the approval of a new drug and not a new cardiovascular indication for weight loss patients generally.
Mounjaro was first approved in the United States in 2022 for type 2 diabetes. Tirzepatide works on both GIP and GLP 1 receptors and has become particularly prominent because of the substantial weight loss it can produce in addition to lowering blood sugar.
There is an unusual technical caveat surrounding the latest decision. At the time of writing, the revised FDA prescribing information and approval letter had not yet appeared in the FDA’s publicly accessible databases. The precise wording of the new indication therefore comes from Lilly’s August 28 announcement, while the approval itself has also been reported by major international wire services.
The heart study involved more than 13,000 patients
The new indication is based on SURPASS CVOT, a large cardiovascular outcomes trial involving 13,299 people with type 2 diabetes and established cardiovascular disease.
Rather than comparing Mounjaro with a placebo, researchers put it up against Trulicity, or dulaglutide, another Eli Lilly diabetes drug that already has proven cardiovascular benefits.
Patients were followed for a median of roughly four years.
During the study, cardiovascular death, nonfatal heart attack or nonfatal stroke occurred in 12.2% of patients receiving Mounjaro, compared with 13.1% receiving Trulicity.
That translates into an 8% lower relative rate of major cardiovascular events with Mounjaro and an absolute difference of 0.9 percentage points.
But there is an important statistical distinction.
The trial successfully demonstrated that Mounjaro was noninferior to Trulicity. In other words, it established that Mounjaro was not meaningfully worse at preventing major cardiovascular events.
It did not establish that Mounjaro was superior to Trulicity. The superiority result did not reach statistical significance.
That makes headlines suggesting that Mounjaro dramatically cuts heart attacks potentially misleading. The study demonstrated cardiovascular protection compared with an already cardioprotective drug, rather than a large additional benefit over another established treatment.
Much more weight loss did not mean significantly fewer heart events
One of the more interesting results may actually be what did not happen.
Patients taking Mounjaro lost considerably more weight than those receiving Trulicity.
Average body weight fell by 11.6% with Mounjaro, compared with 4.5% with Trulicity. Mounjaro also produced a substantially larger reduction in HbA1c, a key measure of long term blood sugar control.
Despite that difference, Mounjaro did not achieve statistically significant superiority for the study’s main cardiovascular endpoint.
That suggests the relationship between weight loss and cardiovascular protection is more complicated than simply assuming that greater weight loss automatically produces proportionally greater protection from heart attacks and strokes.
There were other encouraging findings. All cause mortality was lower among Mounjaro patients, at 8.6% compared with 10.2% for Trulicity. However, because the primary superiority endpoint was not met, secondary findings need to be interpreted more cautiously.
How does Mounjaro compare with Ozempic?
Mounjaro is not the first major diabetes drug to receive an FDA cardiovascular indication.
Novo Nordisk’s injectable Ozempic has carried an indication for reducing major cardiovascular events since 2020 in adults with type 2 diabetes and established cardiovascular disease.
Its pivotal SUSTAIN 6 trial used a different design. Ozempic was compared with placebo rather than another GLP 1 drug with established cardiovascular benefits.
Major cardiovascular events occurred in 6.6% of patients receiving semaglutide compared with 8.9% receiving placebo, representing a 26% relative reduction.
Those percentages should not be used to conclude that Ozempic is necessarily better than Mounjaro. The drugs were tested in separate trials, against different comparators and under different conditions.
Oral semaglutide has also received an FDA cardiovascular indication for adults with type 2 diabetes at high cardiovascular risk.
So the practical significance of the Mounjaro decision is less that doctors suddenly discovered the drug can protect the heart and more that cardiovascular risk reduction is now becoming an officially recognized part of its US regulatory profile.
There is a tradeoff
Mounjaro’s greater effects on weight and blood sugar also came with somewhat more gastrointestinal side effects.
Gastrointestinal adverse events occurred in 42.5% of Mounjaro patients compared with 35.9% of those receiving Trulicity.
Treatment discontinuation because of adverse events was also more common with Mounjaro, at 13.2% compared with 10.1%.
The study did not identify a new long term safety signal.
For doctors and patients, that means treatment decisions are unlikely to come down to cardiovascular data alone. Blood sugar control, desired weight loss, side effects, existing medical conditions, cost and access can all influence which drug makes the most sense.
What does the FDA decision mean in Israel?
For Israelis already taking Mounjaro, the immediate answer is: very little changes.
Mounjaro has been available in Israel since 2024 and is registered for treatment of type 2 diabetes as well as weight management in eligible adults.
But an FDA approval does not automatically alter a drug’s approved indications in Israel.
At the time of writing, the Israeli prescribing information reviewed for Mounjaro does not contain a separate cardiovascular risk reduction indication based on SURPASS CVOT. Any regulatory change would require action through Israel’s Ministry of Health.
There is currently no verified evidence that Lilly has applied for such an indication in Israel.
European regulators have already taken a different approach from the FDA. In June, the European Medicines Agency’s Committee for Medicinal Products for Human Use reviewed the cardiovascular data and acknowledged Mounjaro’s cardiovascular benefit, but did not recommend creating a separate cardiovascular indication. Instead, the new trial data were incorporated into the European product information.
Israel could ultimately take either approach.
Cost remains a bigger issue for many Israeli patients
The more immediate question for many Israelis is access.
Mounjaro is not included in Israel’s national health basket for adult diabetes or obesity treatment, despite being considered during recent basket deliberations.
Patients can obtain it privately, while supplementary health insurance programs offered by the health funds can substantially reduce the cost for eligible patients.
Depending on the health fund, dose, medical indication and insurance coverage, the monthly cost can still amount to hundreds of shekels. Patients purchasing the drug without subsidies can pay considerably more.
That makes the FDA decision medically significant but, for the moment, unlikely to transform access for Israeli patients.
The takeaway
The new approval strengthens the evidence that Mounjaro is more than an effective blood sugar and weight loss treatment for people with type 2 diabetes at high cardiovascular risk.
But it is worth being precise about what was proved.
In a major four year trial, Mounjaro produced substantially greater weight loss and better glucose control than Trulicity while providing at least comparable protection against cardiovascular death, heart attack and stroke. It did not demonstrate statistically superior protection against those cardiovascular events.
And in Israel, nothing changes automatically because of the FDA decision. Mounjaro remains available under its existing Israeli indications, while any cardiovascular label expansion would require a separate regulatory decision by the Ministry of Health.
For patients, the FDA announcement is therefore meaningful evidence about the drug’s cardiovascular profile, not a reason to switch medications without discussing the individual benefits, risks and alternatives with a physician.
