Tirzepatide in Hispanic/Latino Patients With Type 2 Diabetes: A Subgroup Analysis of the SURPASS Program

Abstract

Context: Efficacy and safety of tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, have been studied in patients with type 2 diabetes in the global phase 3 SURPASS program.

Objective: This work aimed to assess the efficacy and safety of tirzepatide in Hispanic/Latino and non-Hispanic/Latino patients in SURPASS-1 to -4 clinical trials.

Methods: A total of 5679 patients were included, 2895 of self-reported Hispanic/Latino ethnicity, in this exploratory analysis of SURPASS-1 to -4 trial data. Interventions included tirzepatide 5, 10, or 15 mg, placebo, or active comparator (semaglutide 1 mg, insulin degludec, and insulin glargine). Change in glycated hemoglobin A1c (HbA1c) and body weight from baseline to week 40 (SURPASS-1 and -2) and to week 52 (SURPASS-3 and -4), and other efficacy and safety outcomes were evaluated within Hispanic/Latino and non-Hispanic/Latino subgroups.

Results: Among Hispanic/Latino and non-Hispanic/Latino patients treated with tirzepatide, respectively, HbA1c decreased significantly from baseline, ranging from 1.9% to 2.7% and 1.7% to 2.5%, and body weight decreased significantly from baseline, ranging from 5.3 kg to 12.4 and 6.5 kg to 17.1 kg (both P < .05) vs comparators across all trials. Subgroup trends were consistent with the overall trial populations. Treatment-emergent adverse events were reported in similar proportions across the subgroups and were primarily gastrointestinal disorders. The incidence of hypoglycemia was low.

Conclusion: Tirzepatide significatively reduced HbA1c and body weight in Hispanic/Latino and non-Hispanic/Latino patients. Tirzepatide was generally well tolerated in both subgroups. Efficacy and safety trends were comparable between subgroups and within the overall trial populations.

Keywords: GIP and GLP-1 receptor agonist; Hispanic/Latino; glycemic control; incretin therapy; tirzepatide; type 2 diabetes.

Figure 1.

A, HbA_1c (%) LSM change from baseline for Hispanic/Latino and non-Hispanic/Latino subgroups and the overall trial population in the SURPASS-1 to -4 trials at end point. End point: SURPASS-1 vs placebo at 40 weeks, SURPASS-2 vs semaglutide at 40 weeks, SURPASS-3 vs insulin degludec at 52 weeks, and SURPASS-4 vs insulin glargine at 52 weeks. Between treatment (tirzepatide dose vs placebo or comparator within population [HL, nHL, overall]) P value * < .05, ** < .001. The HbA_1c LSM change was the LSM change derived from the MMRM within each ethnicity subgroup; the ethnicity P values were derived from the interaction MMRM. MMRM effect of ethnicity P value SURPASS-1 = 0.707, SURPASS-2 = 0.004, SURPASS-3 < 0.001, SURPASS-4 = 0.375. Supplementary Table S2 (12) contains baseline and HbA_1c end points. HbA_1c, glycated hemoglobin A_1c; HL, Hispanic/Latino; LSM, least squares mean; MET, metformin; MMRM, mixed model for repeated measures; nHL, non-Hispanic/Latino; SGLT-2i, sodium-glucose co-transporter-2 inhibitor; SU, sulfonylurea. B, Difference in change from baseline in HbA_1c (%) at end point. Plotted values and 95% CI represent the LSM difference in HbA_1c change between tirzepatide groups and comparators from the MMRM analysis within each ethnicity subgroup; the interaction P value was derived from the interaction MMRM. SURPASS-1 vs placebo at 40 weeks; SURPASS-2 vs semaglutide at 40 weeks; SURPASS-3 vs insulin degludec at 52 weeks; SURPASS-4 vs insulin glargine at 52 weeks. The threshold interaction P value for statistical significance adjusted for multiple comparisons is less than .001.

Figure 2.

A, Weight (kg) LSM change from baseline. B, Percentage LSM change from baseline in body weight (kg). LSM changes are for Hispanic/Latino and non-Hispanic/Latino subgroups in the SURPASS-1 to -4 trials at end point. End point: SURPASS-1 vs placebo at 40 weeks, SURPASS-2 vs semaglutide at 40 weeks, SURPASS-3 vs insulin degludec at 52 weeks, and SURPASS-4 vs insulin glargine at 52 weeks. Between treatment (tirzepatide dose vs placebo or comparator within population [HL, nHL, overall]) P value * < .05, ** < .001. MMRM effect of ethnicity P value SURPASS-1 < 0.001, SURPASS-2 < 0.001, SURPASS-3 = 0.403, SURPASS-4 = 0.533. The weight LSM change was the LSM change derived from the MMRM within each ethnicity subgroup. The ethnicity P values were derived from the interaction MMRM. Supplementary Table S3 (12) contains baseline and weight end points. HL, Hispanic/Latino; LSM, least squares mean; MMRM, mixed-model for repeated measures; nHL, non-Hispanic/Latino; SGLT-2i, sodium-glucose co-transporter-2 inhibitor; SU, sulfonylurea. C, Difference in change from baseline in body weight (kg) at end point. Plotted values and 95% CI represent the LSM difference in body weight change between tirzepatide groups and comparators from the MMRM analysis within each ethnicity subgroup. The interaction P value was derived from the interaction MMRM. SURPASS-1 vs placebo at 40 weeks; SURPASS-2 vs semaglutide at 40 weeks; SURPASS-3 vs insulin degludec at 52 weeks; SURPASS-4 vs insulin glargine at 52 weeks. The threshold interaction P value for statistical significance adjusted for multiple comparisons is less than .001.