In a phase 3 trial of 917 Asia-Pacific patients, all tirzepatide doses were superior to insulin glargine for HbA1c reduction (-2.24 to -2.49% vs. -0.95%) and caused significant weight loss while insulin led to weight gain.
86% reached blood sugar target vs. 24%At 40 weeks, 86% of patients on tirzepatide 10mg achieved HbA1c below 7% — the standard diabetes control target — compared to just 24% on insulin glargine, a more than 3.5-fold difference.
What the researchers found
All three tirzepatide doses were both non-inferior and superior to insulin glargine for HbA1c reduction at week 40:
- Tirzepatide 5mg: -2.24% (treatment difference vs. insulin: -1.29%)
- Tirzepatide 10mg: -2.44% (treatment difference: -1.49%)
- Tirzepatide 15mg: -2.49% (treatment difference: -1.54%)
- Insulin glargine: -0.95%
(All P<0.001)
HbA1c <7.0% targets achieved: tirzepatide 75.4-86.0% vs. insulin 23.7% (P<0.001). Body weight changes: tirzepatide -5.0 to -7.2 kg vs. insulin +1.5 kg (P<0.001). No severe hypoglycemia reported with tirzepatide.
Why it matters
Type 2 diabetes is particularly prevalent in Asia-Pacific populations, where it often develops at lower BMI than in Western populations. This trial is the first to demonstrate tirzepatide's superiority over insulin specifically in a predominantly Chinese/Asian population. The enormous efficacy gap — tirzepatide reduced HbA1c by up to 2.6 times more than insulin — combined with weight loss instead of weight gain could fundamentally change how diabetes is managed in this region, potentially making insulin a second-choice rather than first-line injectable therapy.
How the study worked
SURPASS-AP-Combo was a phase 3, randomized, open-label trial at 66 hospitals in China, South Korea, Australia, and India. Insulin-naive adults with type 2 diabetes uncontrolled on metformin (with or without a sulphonylurea) were randomized 1:1:1:1 to weekly tirzepatide 5mg, 10mg, or 15mg or daily insulin glargine. The primary endpoint was non-inferiority of HbA1c change from baseline to week 40. Key secondary endpoints included superiority testing, HbA1c target achievement rates, and weight change. Of 917 randomized patients, 83.2% were in China.
What this study cannot tell us
The open-label design means both patients and investigators knew which treatment was given, which could influence subjective outcomes. Insulin glargine was titrated to target but the specific titration results and final doses are not detailed — undertitration could have disadvantaged the insulin group. The 40-week duration may not capture long-term outcomes. The predominantly Chinese population (83.2%) limits direct generalizability to other Asia-Pacific ethnic groups. Cost-effectiveness was not assessed — tirzepatide is significantly more expensive than insulin glargine.
How to read the evidence
This is a phase 3 randomized controlled trial published in Nature Medicine with 917 participants — high-quality evidence. The large sample, multiple dose groups, predefined primary and secondary endpoints, and multi-country design are strengths. The open-label design and predominant Chinese enrollment are limitations. The trial was registered and followed standard regulatory trial conduct.
When this study was published
Published in 2023, this trial provides the definitive phase 3 data for tirzepatide in Asia-Pacific populations. Tirzepatide regulatory approvals and clinical adoption in the region have been progressing since this data was published.
The bigger picture
The SURPASS clinical trial program has systematically demonstrated tirzepatide's superiority across multiple comparators — semaglutide, insulin degludec, insulin glargine, and placebo. This Asia-Pacific trial extends the evidence to a population that carries a disproportionate share of the global diabetes burden. The dramatic results raise a fundamental question about the role of insulin in type 2 diabetes management: if a peptide drug delivers better blood sugar control, causes weight loss instead of weight gain, and avoids hypoglycemia, should insulin remain the default injectable escalation?
Questions still open
- Should tirzepatide replace insulin glargine as the preferred injectable escalation after metformin failure in Asia-Pacific populations?
- How do tirzepatide's benefits in Asian patients compare to the effects seen in Western SURPASS trials, given differences in diabetes phenotype?
- What is the cost-effectiveness of tirzepatide versus insulin glargine in healthcare systems across China, India, and other Asia-Pacific countries?
Common questions
How much better is tirzepatide than insulin for type 2 diabetes?
Is tirzepatide safe for Asian patients with type 2 diabetes?
Read the original research
Tirzepatide versus insulin glargine as second-line or third-line therapy in type 2 diabetes in the Asia-Pacific region: the SURPASS-AP-Combo trial.
Nature medicine, 29(6), 1500-1510
Citation
Gao, Leili; Lee, Byung Wan; Chawla, Manoj; Kim, Joshua; Huo, Li; Du, Liying; Huang, Yan; Ji, Linong. (2023). Tirzepatide versus insulin glargine as second-line or third-line therapy in type 2 diabetes in the Asia-Pacific region: the SURPASS-AP-Combo trial.. Nature medicine, 29(6), 1500-1510. https://doi.org/10.1038/s41591-023-02344-1