SURMOUNT-2 topline: up to 15.7% weight loss in people with type 2 diabetes

Eli Lilly reported topline results on April 27, 2023 from SURMOUNT-2, a phase 3 trial testing tirzepatide for weight management in 938 adults who had obesity or overweight and type 2 diabetes ^[1]. After 72 weeks, average weight loss was 13.4% (29.8 lb or 13.5 kg) on the 10 mg dose and 15.7% (34.4 lb or 15.6 kg) on the 15 mg dose, compared with 3.3% (7.0 lb or 3.2 kg) on placebo, using what the company calls the efficacy estimand ^[1].

Tirzepatide is the molecule sold as Mounjaro for type 2 diabetes; it was approved by the FDA under that brand name on May 13, 2022 ^[1]. The obesity version had not been approved at the time of this announcement. Lilly said the trial met both co-primary goals and all key secondary goals for both statistical approaches it used ^[1].

The numbers

Beyond average weight change, 81.6% of participants on 10 mg and 86.4% on 15 mg lost at least 5% of their body weight, versus 30.5% on placebo ^[1][2]. Larger losses were also common: 41.4% (10 mg) and 51.8% (15 mg) lost at least 15% of body weight, compared with 2.6% on placebo ^[1].

The second, more conservative analysis — the treatment-regimen estimand, which counts people regardless of whether they stayed on the drug — showed smaller but still substantial results: 12.8% (10 mg), 14.7% (15 mg) and 3.2% (placebo) average weight loss, with 39.7% and 48.0% of the tirzepatide groups losing at least 15%, versus 2.7% on placebo ^[1].

Participants started with a mean body weight of 222 lb (100.7 kg) and a mean A1C of 8.0% ^[1]. Lilly said the A1C reduction versus placebo was similar to what was seen in the SURPASS diabetes trials ^[1]. Everyone in the drug arms started at 2.5 mg once weekly and stepped up every four weeks to their assigned maintenance dose ^[1].

On safety, Lilly said the profile matched earlier SURMOUNT and SURPASS trials and other incretin drugs approved for obesity ^[1]. The most common side effects were gastrointestinal and generally mild to moderate, mostly during dose escalation. For 10 mg and 15 mg respectively: nausea 20.2% and 21.9%, diarrhea 19.9% and 21.5%, vomiting 10.9% and 13.2%, constipation 8.0% and 9.0% — versus placebo rates of 6.3%, 8.9%, 3.2% and 4.1% ^[1]. Discontinuation because of side effects was 3.8% (10 mg), 7.4% (15 mg) and 3.8% (placebo) ^[1].

Why it matters for patients

Weight loss results in people with type 2 diabetes have historically trailed results in people without it. The contrast is visible within Lilly's own program: SURMOUNT-1, in people with obesity or overweight but no diabetes, reported 22.5% average weight loss, or about 52 lb (24 kg) ^[2]. SURMOUNT-2's top figure was 15.7% ^[1]. The two trials enrolled different people and were not compared head to head, so the gap is a rough signal rather than a direct measurement.

For someone with type 2 diabetes weighing the options, the practical takeaway is what the ranges look like. Roughly 4 in 5 people on the drug lost at least 5% of body weight, and about half on the higher dose lost at least 15% ^[1]. About 3 in 10 on placebo — who also followed a reduced-calorie diet and increased activity — reached 5% ^[1].

These are topline company numbers, not peer-reviewed data. Lilly said full results would be presented at the American Diabetes Association's 83rd Scientific Sessions and submitted to a journal ^[1]. Longer-term durability, results after stopping the drug, and how insurance would cover an obesity indication were not addressed in this announcement.

What happens next

Lilly said it planned to complete its rolling U.S. submission for tirzepatide in adults with obesity or overweight with weight-related conditions "in the coming weeks," and expected "regulatory action as early as late 2023" ^[1][2]. Results from SURMOUNT-3 and SURMOUNT-4 were expected during 2023 ^[1]. The SURMOUNT program has enrolled more than 5,000 people across six registration studies ^[1].

Tirzepatide is also being studied in heart failure with preserved ejection fraction, obstructive sleep apnea, NASH, chronic kidney disease, and obesity-related illness and death ^[1].