SURPASS J-mono and J-combo report Japanese phase 3 results

Two new phase 3 trial results from Japan add to the evidence on tirzepatide, the twice-monthly injectable sold in the United States as Mounjaro for type 2 diabetes and Zepbound for weight management. The SURPASS J-mono trial compared tirzepatide against dulaglutide, while SURPASS J-combo tested tirzepatide added to a single oral diabetes drug. Both were funded by Eli Lilly and Company.^[1][2]

SURPASS J-mono enrolled 636 adults with type 2 diabetes at 46 medical centers in Japan between May 2019 and March 2021.^[1] Participants were randomly assigned to tirzepatide at 5 mg, 10 mg, or 15 mg once weekly, or to dulaglutide 0.75 mg once weekly, for 52 weeks. At week 52, HbA1c — a measure of average blood sugar — dropped by 2.4 to 2.8 percentage points with tirzepatide, compared with 1.3 points for dulaglutide. That works out to a 1.1 to 1.5 percentage point advantage for tirzepatide over dulaglutide, a difference the study authors called statistically significant.^[1]

Weight loss followed a similar pattern. People on tirzepatide lost 5.8 kg to 10.7 kg, or 7.8% to 13.9% of body weight, depending on dose, versus 0.5 kg (0.7%) for those on dulaglutide.^[1] The most common side effects with tirzepatide were nausea, reported by 12% to 20% of participants across doses, constipation in 14% to 18%, and nasopharyngitis, or common cold symptoms, in 14% to 18%. Nausea was reported by 8% of the dulaglutide group.^[1] Ninety-seven percent of participants completed the year-long study.^[1]

SURPASS J-combo took a different approach. It enrolled 443 people at 34 Japanese centers between March 2019 and February 2021 who were already taking a single oral diabetes medication but had inadequately controlled blood sugar.^[2] Tirzepatide, at the same three doses, was added on top of that oral drug for 52 weeks, with safety as the primary focus rather than a head-to-head efficacy comparison. Ninety percent of participants completed treatment. Side effects occurred in 77% of participants overall, more often in the 15 mg group (84%) than the 5 mg or 10 mg groups (74% each). The most frequent reactions were nasopharyngitis (17%), nausea (17%), constipation (12%), diarrhea (12%), and decreased appetite (10%). No deaths were confirmed by the study's review process.^[2]

In the combo trial, HbA1c fell from a baseline near 8.5% to between 5.6% and 6.0% across the three doses by week 52, and body weight dropped 3.8 kg to 10.2 kg, or 5.1% to 13.2%, depending on dose.^[2]

Why it matters for patients

Both studies were conducted in Japanese patients, a population that may respond differently to diabetes drugs than patients elsewhere. Even so, the results are broadly consistent with tirzepatide trials run in other countries, adding to the overall picture of how the drug performs for blood sugar control and weight loss at different doses. For US patients already using Mounjaro or Zepbound, or considering them, this data offers another data point on typical side effects — mainly gastrointestinal issues like nausea and constipation — and on how effects can scale with dose. The J-combo results in particular suggest tirzepatide can be added safely to an existing oral diabetes medication rather than replacing it outright, though the specific oral drugs tested and their doses are not detailed in the available summaries.^[1][2]

An accompanying editorial in the same journal described tirzepatide's dual mechanism, targeting both GIP and GLP-1 receptors, as a notable advance, though it is not detailed here beyond that framing.^[1][2]

What happens next

The published trial reports do not specify a timeline for regulatory review in Japan or elsewhere based on this data. It is not yet known from these sources how or whether this Japanese trial data influenced tirzepatide's US labeling or dosing guidance.