Background and Rationale
Type 2 diabetes mellitus (T2DM) continues to be a major public health challenge globally, with a rapidly growing burden in China due to lifestyle changes and urbanization. Optimal glycemic control is critical to prevent complications associated with the disease. Basal insulin therapy is a commonly used treatment for patients with inadequate glycemic control on oral agents; however, intensification strategies remain a clinical need to enhance therapeutic effects without compromising safety.
Tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 receptor (GLP-1R) agonist, has shown promise in improving glycemic parameters and promoting weight loss in diverse populations. While evidence exists from global SURPASS trials, data specific to Chinese patients with T2DM treated with basal insulin were lacking. This prompted the SURPASS-CN-INS study to evaluate tirzepatide’s efficacy and safety when added to basal insulin within this population.
Study Design and Methods
SURPASS-CN-INS was a robust, multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial conducted across 26 hospitals in China over a 40-week period. Eligible participants were adults aged 18 years or older diagnosed with inadequately controlled T2DM receiving daily insulin glargine therapy, either alone or combined with metformin and optionally an SGLT2 inhibitor.
Participants were randomly assigned in a 1:1:1:1 ratio to one of four groups receiving subcutaneous injections once weekly: tirzepatide 5 mg, 10 mg, or 15 mg, or placebo. Randomization was stratified by baseline HbA1c (≤8.0% vs >8.0%) and SGLT2 inhibitor use via an interactive web response system to ensure balanced distribution. Both participants and study personnel, including investigators and clinical monitors, were blinded to treatment assignments using identical packaging and injection devices.
The primary efficacy endpoint focused on the change in glycated hemoglobin (HbA1c) from baseline to week 40 comparing tirzepatide 10 mg and 15 mg to placebo. The analysis population included all randomized patients who received at least one dose of study treatment, excluding those mistakenly enrolled. Safety analyses encompassed all patients receiving at least one dose.
Participant Characteristics
A total of 331 patients were screened between February 5, 2023, and July 1, 2024, with 257 randomized and treated: 65 received tirzepatide 5 mg, 65 received 10 mg, 63 received 15 mg, and 64 received placebo. Two patients (one in the tirzepatide 5 mg and one placebo group) were excluded due to inadvertent enrollment.
The analyzed efficacy cohort of 255 patients had a mean age of 56.7 years (±10.5), with 38% female and 62% male representation. Baseline HbA1c levels and other demographic factors were balanced across groups.
Results: Glycemic Control Effectiveness
At week 40, patients receiving tirzepatide 10 mg and 15 mg demonstrated pronounced reductions in HbA1c compared to placebo. Specifically, the mean HbA1c reduction was -2.39% (SE 0.13) and -2.37% (SE 0.13) for 10 mg and 15 mg groups, respectively, versus -0.91% (SE 0.12) in the placebo group. These differences were statistically significant, with mean treatment differences of -1.48% (97.5% CI -1.87 to -1.08; p < 0.0001) and -1.45% (-1.85 to -1.06; p < 0.0001) for 10 mg and 15 mg respectively.
This reflects a robust improvement in glycemic control, affirming the therapeutic potential of tirzepatide as an adjunct to basal insulin.
Safety and Tolerability
The safety profile of tirzepatide was generally favorable. The most common treatment-emergent adverse events (TEAEs) among tirzepatide recipients were gastrointestinal (GI) in nature, consistent with the drug’s mechanism of action. The primary GI events included diarrhoea, decreased appetite, nausea, and vomiting, mostly mild to moderate and transient.
Diarrhoea was reported in 26% of the 5 mg group, 37% of the 10 mg group, and 37% of the 15 mg group, compared with 8% in the placebo arm. Decreased appetite affected 29%, 25%, and 32% of the tirzepatide groups respectively, with none reported in placebo. Upper respiratory tract infection was a common non-gastrointestinal event, occurring at similar rates across groups.
Importantly, severe adverse events were uncommon, and no new safety concerns emerged. These findings align with prior global trial data but provide important confirmation within the Chinese T2DM patient context.
Clinical Implications and Future Directions
The addition of tirzepatide to basal insulin regimens offers a compelling option for intensified glycemic management in Chinese patients with T2DM. Its dual agonist mechanism addresses multiple pathophysiological pathways, promoting improved glucose regulation and body weight control.
Given the rising diabetes prevalence in China, integrating tirzepatide into clinical practice could help reduce the risk of microvascular and macrovascular complications associated with poor glycemic control. Further real-world studies and long-term follow-up data will be valuable to confirm durability and cardiovascular safety.
Conclusion
SURPASS-CN-INS provides strong clinical evidence that tirzepatide, when added to basal insulin, significantly improves HbA1c levels and is well tolerated among Chinese patients with T2DM. This trial supports tirzepatide’s therapeutic role in enhancing glycemic outcomes and expanding medical treatment options tailored to this population.
Funding and Disclosures
This study was funded by Eli Lilly and Company. The authors declare adherence to ethical standards, and the study was registered under ClinicalTrials.gov (NCT05691712).
Reference
Guo L, Dong X, Ma J, Liu M, Lu Y, Wang H, Li Q, Li L, Deng Y, Xu J. Efficacy and safety of tirzepatide added to basal insulin in patients with type 2 diabetes in China (SURPASS-CN-INS): a double-blind, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2025 Dec;13(12):1015-1029. doi: 10.1016/S2213-8587(25)00248-7. Epub 2025 Oct 27. PMID: 41167231.
