Research · Single-study breakdown
Foundayo's ACHIEVE-4 cardiovascular data: 57% lower all-cause death, non-inferior MACE, and meaningful A1C/weight benefits
What this means for you
- This was a safety and comparison study, not a study of every possible outcome. It compared Foundayo against insulin specifically, not against other GLP-1 drugs already on the market, like Ozempic or Mounjaro.
- It also does not tell you how Foundayo will work for you personally. Trial averages describe a group, not an individual.
- This is also not advice to start, stop, or switch any medication. If you take insulin now and are curious whether an alternative makes sense for you, that is a conversation for you and your doctor, based on your own health history, not on a headline.
What the study actually tested
This was a head-to-head trial. Half the people took Foundayo, a once-daily pill. The other half took insulin glargine, a long-acting injected insulin that doctors have used safely for decades. Insulin was dosed up over time, the normal way doctors manage it.
The study’s main question was about safety, not benefit: does the new drug cause more heart attacks, strokes, or cardiovascular deaths than the insulin people already trust? This is called a “non-inferiority” test. It is not designed to prove one drug works better. It is designed to prove the new drug is not worse.
On that measure, Foundayo passed. The rate of major heart problems (what researchers lump together as MACE, for “major adverse cardiac events”) was not meaningfully different between the two drugs. The hazard ratio was 0.84, with a range that included the possibility of no difference at all. In plain terms: using this drug does not appear to raise your risk of a heart attack or stroke compared with insulin, and it may even lower it slightly, but the study was not built to prove that second part.
The number getting attention: fewer deaths
Here is the finding driving headlines. People taking Foundayo had a lower rate of death from any cause during the study, compared with people on insulin. The hazard ratio was 0.43, meaning the rate of death in the drug group was well under half the rate in the insulin group. The result was statistically strong (p=0.002, for anyone checking the math), which means it is unlikely to be chance alone.
This is a real, measured result from a real clinical trial in people, not a study in animals and not a guess. But “real” and “fully explained” are different things. The trial was not designed with all-cause death as its main question, so while the finding is statistically solid, researchers do not yet have a settled explanation for why the gap was this large. It could reflect the heart and kidney benefits, the weight loss, or some combination not yet pinned down. We do not know yet whether this exact size of benefit will hold up in future, larger studies designed specifically to test it.
The other numbers, for context
Over the 52-week main study period, people on Foundayo also saw:
- A1C (a 3-month average blood sugar measure) dropped by 1.6 percentage points, versus 1.0 for insulin
- Average weight loss of 8.8%, versus an average weight gain of 1.7% on insulin
- Blood pressure, triglycerides, and a marker of inflammation (hsCRP) all moved in a favorable direction
- Kidney function, measured by eGFR, declined more slowly on Foundayo than on insulin
Longer-term data, out to 104 weeks, showed more than half of people on Foundayo reached an A1C of 6.5% or lower, compared with about a quarter on insulin.
Side effects were mostly digestive — nausea, vomiting, and diarrhea were the most common complaints, and about 1 in 10 people stopped the drug because of side effects.
What this study can't tell us
- A safety test, not a best-drug test — the main question was whether the new drug is not worse than insulin for heart attacks, strokes, and cardiovascular deaths, not whether it works better than anything.
- Compared against insulin only — not against other GLP-1 drugs already on the market, like Ozempic or Mounjaro.
- All-cause death was not the trial’s main question — the finding is statistically solid (p=0.002), but researchers do not yet have a settled explanation for why the gap was this large, and it is not known whether this size of benefit will hold up in future, larger studies designed specifically to test it.
- Trial averages describe a group, not an individual — none of this is advice to start, stop, or switch any medication. That is a conversation with your doctor, based on your own health history.
Most type 2 diabetes drug trials are built to show a new drug does not increase heart risk, and most clear that bar without much drama. A trial that also shows a sizeable drop in deaths from any cause, with a pill that is easier for many people to take than an injection, is a genuinely different kind of result. It does not mean the question is settled. It means it is now a question worth the research community building further, larger studies to actually answer.
Sources
- Lilly's oral GLP-1 Foundayo (orforglipron) demonstrated cardiovascular safety alongside sustained A1C reduction and weight loss in its largest and longest type 2 diabetes study — PR Newswire (Eli Lilly) (2026)
- The Lancet publication of the ACHIEVE-4 trial — The Lancet (2026)
- ACHIEVE-4 trial design (preprint) — arXiv (2026)
Not medical advice. Educational summary of published research. Last reviewed Oct 21, 2026.