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.

BACKGROUND: Data on tirzepatide added to basal insulin in patients with type 2 diabetes in China are scarce. We aimed to evaluate the efficacy and safety of tirzepatide added to basal insulin in this population. METHODS: SURPASS-CN-INS was a 40-week, double-blind, multicentre, randomised, placebo-controlled, phase 3 trial done in 26 hospitals in China. Participants aged 18 years or older with uncontrolled type 2 diabetes receiving once-daily insulin glargine alone or in combination with metformin with or without an SGLT2 inhibitor were randomly assigned (1:1:1:1) to once-weekly tirzepatide 5 mg, 10 mg, or 15 mg, or placebo by subcutaneous injection for 40 weeks, stratified by HbA(≤8·0% [≤64 mmol/mol] vs >8·0% [>64 mmol/mol]) and SGLT2 inhibitor use using an interactive web response system. Treatment assignment was masked from the study sponsor, investigators, site staff, clinical monitors, and patients until the end of the study by using identical packaging and injection devices for tirzepatide and placebo. The primary endpoint was change in HbAfrom baseline to week 40 for tirzepatide 10 mg or 15 mg versus placebo in all randomly assigned patients receiving at least one dose of treatment, excluding those who were enrolled inadvertently. Safety was evaluated in all randomly assigned patients receiving at least one dose of treatment. The study was registered with ClinicalTrials.gov, NCT05691712, and has been completed. FINDINGS: Between Feb 5, 2023, and July 1, 2024, 331 patients were screened, of whom 257 were randomly assigned to and received tirzepatide 5 mg (n=65), 10 mg (n=65), or 15 mg (n=63), or placebo (n=64). One patient in the tirzepatide 5 mg group and one in the placebo group were inadvertently enrolled and excluded from efficacy analyses. The mean age of 255 patients in the efficacy analysis set was 56·7 years (SD 10·5). 98 (38%) patients were female, and 157 (62%) patients were male. Patients receiving tirzepatide had greater reductions in HbAfrom baseline at week 40 than those receiving placebo (-2·39% [SE 0·13] in the 10 mg group, and -2·37% [0·13] in the 15 mg group vs -0·91% [0·12] in the placebo group; difference vs placebo -1·48% [97·5% CI -1·87 to -1·08; p<0·0001] for the 10 mg group and -1·45% [-1·85 to -1·06; p<0·0001] for the 15 mg group). The most common treatment-emergent adverse events among patients receiving tirzepatide were diarrhoea (17 [26%; 95% CI 17-38] of 65 in the tirzepatide 5 mg group, 24 [37%; 26-49] of 65 in the tirzepatide 10 mg group, and 23 [37%; 26-49] of 63 in the tirzepatide 15 mg group vs five [8%; 3-17] of 64 in the placebo group), decreased appetite (19 [29%; 20-41], 16 [25%; 16-36], and 20 [32%; 22-44] vs none [0%; 0-6]), and upper respiratory tract infection (13 [20%; 12-31], 11 [17%; 10-28], and 11 [18%; 10-29] vs ten [16%; 9-26]). Gastrointestinal adverse events commonly reported in other trials in the SURPASS programme, including diarrhoea, nausea (three [5%; 95% CI 2-13] in the tirzepatide 5 mg group, seven [11%; 5-21] in the tirzepatide 10 mg group, and seven [11%; 5-21] in the tirzepatide 15 mg group vs two [3%; 1-11] in the placebo group), and vomiting (four [6%; 2-15], six [9%; 4-19], and four [6%; 3-15] vs none [0%; 0-6]), were predominantly mild or moderate in severity. INTERPRETATION: Tirzepatide added to basal insulin improved glycaemic control and was generally well tolerated, providing evidence to support its potential therapeutic use in patients with type 2 diabetes in China. FUNDING: Eli Lilly and Company. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.