Tirzepatide beats insulin glargine in Asia-Pacific type 2 diabetes trial
A head-to-head trial found the tirzepatide molecule cut blood sugar more and reduced weight instead of adding it, compared with a common insulin, though the study did not include US sites.
In a phase 3 trial published May 25, 2023, adults with type 2 diabetes in the Asia-Pacific region who took weekly tirzepatide had larger drops in blood sugar than those who took daily insulin glargine — and they lost weight while the insulin group gained it [1].
What the trial found
The study, called SURPASS-AP-Combo, randomized 917 insulin-naive adults whose type 2 diabetes was not controlled on metformin, with or without a sulfonylurea [1]. Participants were assigned to tirzepatide 5 mg, 10 mg or 15 mg once a week, or to insulin glargine once a day, at 66 hospitals in China, South Korea, Australia and India. Most participants — 763, or 83.2% — were in China [1].
At week 40, average HbA1c fell by 2.24 percentage points with tirzepatide 5 mg, 2.44 points with 10 mg and 2.49 points with 15 mg, compared with 0.95 points with insulin glargine. The differences between tirzepatide and insulin ranged from 1.29 to 1.54 percentage points, and all were statistically significant [1].
More people reached an HbA1c below 7.0% on tirzepatide: 75.4% at 5 mg, 86.0% at 10 mg and 84.4% at 15 mg, versus 23.7% on insulin glargine [1].
Body weight moved in opposite directions. Average weight change at week 40 was a loss of 5.0 kg (6.5%) with tirzepatide 5 mg, 7.0 kg (9.3%) with 10 mg and 7.2 kg (9.4%) with 15 mg. The insulin glargine group gained an average of 1.5 kg, or 2.1% [1].
Side effects
The most common adverse events reported with tirzepatide were mild to moderate decreased appetite, diarrhea and nausea. No severe hypoglycemia was reported in the trial [1]. Rates of each side effect by dose were not included in the published summary of results.
Why it matters for patients
Insulin is a frequent next step when pills are no longer enough, so trials that compare a newer drug directly against insulin answer a practical question rather than a theoretical one [1]. In this trial, the two treatments differed not only in how much they lowered HbA1c but in which direction weight moved — a gap of several kilograms between the tirzepatide groups and the insulin group over 40 weeks [1].
There are limits to what this trial shows. It enrolled people in China, South Korea, Australia and India, not the United States, so the results may not apply identically to a US population [1]. It tested tirzepatide against insulin glargine only — no comparison with semaglutide or other GLP-1 medications was reported. Everyone in the study was insulin-naive, meaning the findings do not directly describe people who already take insulin. The publication does not address cost, insurance coverage or how the drugs were tolerated over a longer period.
Tirzepatide is the molecule in Mounjaro and Zepbound; insulin glargine is a long-acting insulin. The trial used weekly injections for tirzepatide and daily injections for insulin glargine [1]. Whether that schedule difference matters to any individual is a question for a clinician, not something the trial measured.
What happens next
The trial is registered on ClinicalTrials.gov as NCT04093752 [1]. Whether these results will change US prescribing labels or guidance has not been disclosed. Longer-term data on heart, kidney and other outcomes were not reported in this publication, and the study summary does not describe what happened to participants after week 40 [1].
Sources
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