Following an impressive data drop this summer highlighting the potential for Eli Lilly’s tirzepatide to stave off progression to Type 2 diabetes in prediabetic patients, the Indianapolis-based drugmaker is laying out full results from its longest completed study of the dual GIP/GLP-1 receptor agonist to date.

In the three-year SURMOUNT-1 trial, tirzepatide curbed the risk of disease progression to Type 2 diabetes by 94% versus placebo in adult prediabetes patients who were obese or overweight, Lilly said in a release Wednesday. The number represents a pooled result from three tirzepatide doses (5 mg, 10 mg and 15 mg) studied in the trial.

Putting those results into perspective, one new case of diabetes could be prevented for every nine patients treated with tirzepatide, which is marketed in the U.S. as Mounjaro for Type 2 diabetes and as Zepbound for obesity, Lilly said.

Overall, nearly 99% of patients on tirzepatide remained diabetes-free at the end of the trial’s 176-week treatment period, the company added. 

Further, at the 193-week mark, which followed a 17-week off-treatment follow-up period, only 2.4% of patients on Lilly’s drug were diagnosed with Type 2 diabetes compared to 13.7% of patients in the study’s placebo cohort.

As reported in August, the highest dose of tirzepatide tested—15 mg—also helped patients lose an average of 22.9% of their body weight, versus just 2.1% in the trial’s control arm.

Patients on the 5-mg and 10-mg doses of tirzepatide saw average weight reductions of 15.4% and 19.9%, respectively. Patients were able to maintain that weight loss throughout the trial’s three-year run, Lilly pointed out.

“These results underscore the critical role of long-term therapy with effective treatments like tirzepatide to achieve and maintain weight reduction,” Jeff Emmick, M.D., Ph.D., senior vice president of product development at Lilly, said in a statement.

Aside from the SURMOUNT-1 study’s primary goals around weight loss and diabetes prevention, tirzepatide also succeeded across a number of additional endpoints, with the drug linked to improvements in glycemic control and cardiometabolic risk factors like fasting insulin and blood pressure as well as “health-related quality of life,” Lilly said.

Safety and tolerability for tirzepatide were on par with the drug’s profile in other clinical trials. The most frequently reported adverse event in the study was COVID-19, followed by largely mild-to-moderate gastrointestinal side effects like nausea, diarrhea and constipation.

Lilly’s phase 3 study enrolled a total of 1,032 patients with prediabetes and randomized them to receive one of the three doses of tirzepatide or placebo as an adjunct to a reduced-calorie diet and increased physical activity. Patients in the trial also had either hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease or some combination of those comorbidities.

Lilly published the full results from SURMOUNT-1 in The New England Journal of Medicine and recently presented the detailed readout at ObesityWeek 2024 in San Antonio.

Tirzepatide has racked up several impressive data sets this year, signaling the potential for expansions beyond the medicine’s bread-and-butter indications in diabetes and obesity.

In early August, tirzepatide passed muster in the late-stage SUMMIT trial by cutting the risk of adverse heart failure outcomes—such as hospitalization or cardiovascular death—by 38% compared to placebo. The drug also improved patients' heart failure symptoms and physical limitations versus a dummy drug, Lilly said.

Results from that study—which enrolled 731 patients with heart failure with preserved ejection fraction and obesity—have prompted Lilly to submit the data to the FDA and other regulators sometime before the year is out.

In addition, Lilly released results from the phase 2 SYNERGY-NASH trial in June. That study showed that 54.9% of patients on tirzepatide 5 mg, 51.3% of patients on tirzepatide 10 mg and 51% of patients on tirzepatide 15 mg experienced at least one stage of fibrosis improvement without their metabolic dysfunction-associated steatohepatitis (MASH) worsening.

That compared with just 29.7% of MASH patients in the placebo group who experienced the same outcome. MASH, formerly known as nonalcoholic steatohepatitis, or NASH, results in liver inflammation caused by excess fat cells in the organ.

Despite tirzepatide’s winning streak in the clinic—plus clearance of protracted supply issues early last month—it hasn’t all been smooth sailing for the metabolic blockbuster this year.

In 2024’s third quarter, sales of Mounjaro in Type 2 diabetes came in at $3.11 billion, falling short of a $3.7 billion analyst projection. The situation was much the same for Zepbound in obesity, which saw sales clock in at $1.26 billion versus a $1.7 billion estimate.

Those results underwhelmed given Mounjaro’s massive leap from $1.81 billion in first-quarter sales to $3.09 billion in the second quarter. Zepbound, for its part, grew revenue from $517 million to $1.24 billion over that same six-month stretch.

In light of those sales figures, Lilly removed $600 million from the top end of its annual revenue projection, bringing the projected sum down to $46 billion for all of 2024. 

Still, Lilly execs seemed far from worried when discussing the results with analysts on the company's third-quarter earnings call.

“The underlying market for both type 2 (diabetes) and obesity continues to grow," Lilly’s president of cardiometabolic health Patrik Jonsson explained. "We took a more prudent approach than we anticipated in Q3, pretty much driven by the need to deliver a good consumer experience." 

Jonsson added that Lilly is “investing heavily” in direct-to-consumer efforts for tirzepatide, while the president of Lilly International, Ilya Yuffa, said new launches overseas should begin to bring in more sales in the fourth quarter.