SURPASS-AP-Combo reports Asia-Pacific results against insulin glargine

A phase 3 trial called SURPASS-AP-Combo tested tirzepatide against insulin glargine in 917 adults with type 2 diabetes who had never used insulin before. The study ran at 66 hospitals in China, South Korea, Australia and India, with the vast majority of participants, 763 of 917, enrolled in China ^[1]. Tirzepatide is the active ingredient in Mounjaro and Zepbound. It is a once-weekly injection that acts on two gut hormone pathways, GIP and GLP-1 ^[1].

Participants took metformin, with or without a sulfonylurea, and still had blood sugar that was not well controlled. They were randomly assigned to one of three tirzepatide doses, 5 mg, 10 mg or 15 mg weekly, or to daily insulin glargine that was adjusted upward over time ^[1]. After 40 weeks, all three tirzepatide doses lowered HbA1c, a measure of average blood sugar, more than insulin glargine did. The gap ranged from 1.29 to 1.54 percentage points, and every comparison was statistically significant ^[1].

More people on tirzepatide reached the common treatment goal of an HbA1c below 7.0%. That happened in 75.4% of people on the 5 mg dose, 86.0% on 10 mg and 84.4% on 15 mg, compared with just 23.7% of people on insulin glargine ^[1].

The weight results moved in opposite directions. People on tirzepatide lost 5.0 kg to 7.2 kg, depending on dose, about 11 to 16 pounds. People on insulin glargine gained 1.5 kg, or roughly 3.3 pounds, a 2.1% increase in body weight ^[1]. The most common side effects with tirzepatide were mild to moderate decreased appetite, diarrhea and nausea. No cases of severe low blood sugar were reported in the trial ^[1].

Why it matters for patients

This trial adds evidence from an Asia-Pacific population, which differs from the mostly Western populations in many earlier tirzepatide studies. The results echo a pattern seen elsewhere: tirzepatide lowered blood sugar more than insulin while also reducing body weight, whereas insulin glargine is known to often cause weight gain as a side effect of tighter blood sugar control ^[1].

For people with type 2 diabetes who have not yet started insulin, these findings offer a data point about how tirzepatide compares with a standard basal insulin option in terms of blood sugar control, weight change and short-term safety signals like hypoglycemia. The absence of severe hypoglycemia in this trial is notable, since that risk is a common concern with insulin therapy ^[1]. The side effect profile of tirzepatide, mainly digestive symptoms like nausea and diarrhea, was consistent with what has been reported in other tirzepatide studies.

It is not yet known from this source how these results compare across the four countries individually, since the published data are pooled. It is also not stated in this source how long these effects lasted beyond the 40-week study period, or whether the findings would extend to populations outside Asia-Pacific in the same way. This trial focused specifically on people who had not previously used insulin, so it does not address how tirzepatide performs as an add-on for people already on insulin.

What happens next

The study was registered as NCT04093752 and the results were published in 2023 ^[1]. Related analyses have already followed, including a 2024 subgroup study examining how outcomes varied by starting body mass index ^[1]. Broader reviews and meta-analyses combining this trial with other tirzepatide research continue to be published as researchers work to understand how the drug performs across different populations and in comparison with other treatments.