The numbers on the scale may be shrinking, but the buzz around Eli Lilly’s experimental obesity and diabetes drug is only getting bigger.
Newly released data shows the yet-to-be-approved shot helped patients shed more than twice as much weight as Ozempic’s highest approved dose in a head-to-head clinical trial.
The next-generation treatment, called retatrutide, also outperformed its rival at lowering blood sugar, boosting its blockbuster potential in the increasingly crowded obesity and diabetes market.
“Head-to-head trials show patients and physicians how a potential new medicine compares with treatments that are available and reimbursed today,” Dr. Kenneth Custer, Lilly’s executive vice president, said in a press release.
“Based on these results and those from across our Phase 3 program, we believe retatrutide, if approved, could shift the treatment paradigm for people living with type 2 diabetes, obesity and related cardiometabolic conditions.”
The experimental shot is the latest heavy hitter in Lilly’s drug pipeline. If approved, it would join the company’s popular treatments Mounjaro and Zepbound.
Both of those drugs work by mimicking two gut hormones — GLP-1 and GIP — that help regulate blood sugar, curb appetite and slow digestion.
Retatrutide takes the science a step further. Nicknamed “Triple G,” it targets those same two pathways while also activating glucagon, a third hormone involved in fat burning.
The latest trial pitted two weekly doses of retatrutide — 9 milligrams and 12 milligrams — against a 2-milligram dose of Novo Nordisk’s Ozempic, the drug’s highest approved dose for type 2 diabetes.
Nearly 1,300 adults with type 2 diabetes participated in the study. At the outset, their average A1C — a measure of blood sugar levels over roughly the previous three months — was 8.3%.
After 80 weeks, participants taking either dose of retatrutide saw their A1C fall by an average of 2.2 percentage points, compared with a 1.8-point drop among those taking Ozempic.
The drug made an even bigger splash on the scale.
Patients taking the 9-milligram dose of retatrutide shed an average of 44.3 pounds, or 19.5% of their body weight. Those on the 12-milligram dose lost an average of 47.4 pounds, or 20.9%.
Ozempic, meanwhile, helped participants lose an average of 20.9 pounds, or 9.4% of their body weight.
Lilly said its experimental drug also outperformed Ozempic on several cardiovascular risk factors, including non-HDL cholesterol, triglycerides and systolic blood pressure.
As with other drugs in the GLP-1 family, retatrutide’s most common side effects involved the gastrointestinal tract.
Digestive problems were generally similar between the two groups, though diarrhea was slightly more common among retatrutide users, while constipation cropped up more often among those taking Ozempic.
Retatrutide users also reported somewhat higher rates of dysesthesia, an unusual sensation that can feel like tingling, burning or skin that’s on fire.
Lilly said most adverse events were mild to moderate and typically resolved during treatment.
Still, more patients dropped out of the trial while taking retatrutide than Ozempic. Discontinuation rates were 4.8% for the 9-milligram dose and 7.9% for the 12-milligram dose, compared with 2.7% for Ozempic.
The latest results add to a growing body of evidence that retatrutide could be a major contender in the next generation of obesity drugs.
In an earlier trial involving people with obesity or who were overweight, participants taking the highest dose — 12 milligrams weekly — lost an average of 71.2 pounds, or 28.7% of their body weight, over 68 weeks.
The drug also made headlines in February after reports of higher dropout rates raised questions about tolerability, with some participants reportedly concerned about how much weight they were losing.
The medication has earned the nickname “King Kong” for its potency. But research suggests patients may not need to go all the way to the top dose to see substantial results.
In another study, participants taking a lower 4-milligram dose lost an average of 29.8 pounds, or 12.7% of their body weight, over 80 weeks.
Lilly expects to submit retatrutide to the Food and Drug Administration for approval early next year. But in the meantime, some consumers aren’t waiting for the government’s blessing.
Unapproved versions of retatrutide have flooded the gray-market peptide space, attracting everyone from menopausal women to “looksmaxxing” teens.
Lilly has warned against using these knockoffs and is suing multiple companies it accuses of illegally selling versions of its drug.
The FDA has also cautioned consumers about these products often marketed online as “for research use only,” warning that they may pose serious health risks.
Earlier this month, news broke that the agency had received reports of at least two deaths linked to products claiming to contain retatrutide.
Reported complications included cardiac arrest, severe dehydration and malnutrition.
