Tirzepatide added to basal insulin cut HbA1c by 1.5 points in a China trial

Most of what is known about tirzepatide in people already taking basal insulin comes from trials run largely outside China. A phase 3 trial published in The Lancet Diabetes & Endocrinology on October 27 addresses that gap directly, and its stated premise is that data in this population in China are scarce [s1].

The design

SURPASS-CN-INS was a 40-week, double-blind, multicentre, randomised, placebo-controlled trial conducted at 26 hospitals in China [s1]. Eligible participants were aged 18 or older with uncontrolled type 2 diabetes on once-daily insulin glargine, alone or with metformin, with or without an SGLT2 inhibitor [s1].

They were randomised 1:1:1:1 to once-weekly subcutaneous tirzepatide at 5 mg, 10 mg or 15 mg, or to placebo, for 40 weeks [s1]. Randomisation was stratified by baseline HbA1c — at or below 8.0% versus above — and by SGLT2 inhibitor use [s1]. Masking extended to the sponsor, investigators, site staff, clinical monitors and patients, maintained with identical packaging and injection devices [s1].

The primary endpoint was the change in HbA1c from baseline to week 40 for the 10 mg or 15 mg doses versus placebo [s1].

Between February 5, 2023 and July 1, 2024, 331 patients were screened and 257 were randomised and treated: 65 to tirzepatide 5 mg, 65 to 10 mg, 63 to 15 mg and 64 to placebo [s1]. Two patients — one on 5 mg and one on placebo — were enrolled inadvertently and excluded from the efficacy analysis, leaving 255 [s1]. Mean age was 56.7 years (SD 10.5); 98 participants (38%) were female and 157 (62%) male [s1].

The result

HbA1c fell by 2.39% (SE 0.13) in the 10 mg group and 2.37% (SE 0.13) in the 15 mg group, against 0.91% (SE 0.12) on placebo [s1]. The differences versus placebo were -1.48% (97.5% CI -1.87 to -1.08; p<0.0001) for 10 mg and -1.45% (-1.85 to -1.06; p<0.0001) for 15 mg [s1].

The two higher doses were, on this endpoint, indistinguishable from one another. That is worth noting because dose escalation in incretin therapy is usually framed as buying additional glycaemic effect; here the increment from 10 mg to 15 mg did not.

The tolerability picture

The most common treatment-emergent adverse events on tirzepatide were diarrhoea, decreased appetite and upper respiratory tract infection [s1].

Diarrhoea affected 17 of 65 (26%; 95% CI 17-38) on 5 mg, 24 of 65 (37%; 26-49) on 10 mg and 23 of 63 (37%; 26-49) on 15 mg, against five of 64 (8%; 3-17) on placebo [s1]. Decreased appetite affected 19 (29%; 20-41), 16 (25%; 16-36) and 20 (32%; 22-44) respectively, against none on placebo [s1]. Upper respiratory tract infection was reported by 13 (20%), 11 (17%) and 11 (18%) on tirzepatide and ten of 64 (16%) on placebo — the one common event with no clear separation from placebo [s1].

Nausea and vomiting, prominent in other SURPASS trials, were less frequent here: nausea in three (5%), seven (11%) and seven (11%) on tirzepatide versus two (3%) on placebo, and vomiting in four (6%), six (9%) and four (6%) versus none [s1]. Gastrointestinal events were predominantly mild or moderate [s1].

The authors conclude that tirzepatide added to basal insulin improved glycaemic control and was generally well tolerated, supporting its potential therapeutic use in patients with type 2 diabetes in China [s1]. An accompanying commentary in the same issue took up the clinical and research implications of dual incretin therapy for type 2 diabetes inadequately controlled on basal insulin in Chinese adults [s2].

What the trial cannot settle

At 255 participants in the efficacy analysis, this is a modestly sized trial, and the confidence intervals on adverse-event rates are correspondingly wide — the diarrhoea estimate on 10 mg spans 26% to 49% [s1].

Forty weeks is short relative to the horizon over which type 2 diabetes is managed. The trial reports glycaemic control and tolerability, not cardiovascular or kidney outcomes, and a placebo comparator answers whether adding tirzepatide helps rather than how it compares with intensifying insulin or adding another agent.

The trial was funded by Eli Lilly and Company, tirzepatide's manufacturer [s1]. That is standard for phase 3 registration trials and is disclosed; the masking arrangements described above are the relevant safeguard.

What to watch

Whether regulators in China act on this evidence; whether longer follow-up shows the 10 mg and 15 mg doses continue to converge on glycaemic endpoints, which would bear on dose selection; and whether the lower rates of nausea and vomiting relative to other SURPASS trials reflect a genuine population difference or the smaller sample.

This article describes a single randomised trial and is informational only. It is not medical advice, and nothing here should be used to start, stop or change any diabetes treatment.

Sources

• [s1] 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, The Lancet Diabetes & Endocrinology, 2025;13(12):1015-1029, published online 2025-10-27. ClinicalTrials.gov NCT05691712.
• [s2] Dual incretin therapy for type 2 diabetes inadequately controlled on basal insulin in Chinese adults: clinical and research implications, The Lancet Diabetes & Endocrinology, 2025;13(12):989-990, published online 2025-10-27.