Improved HbA1c and body weight in GADA-positive individuals treated with tirzepatide: A post hoc analysis of SURPASS

Context: People with clinically diagnosed type 2 diabetes (T2D) but positive antiglutamic acid decarboxylase autoantibodies (GADA), referred to here as latent autoimmune diabetes in adults (LADA), may experience more rapid glycemic deterioration than those with T2D and may benefit from effective diabetes treatment with additional metabolic benefits. Objective: This work aimed to assess glycated hemoglobin A(1c) (HbA(1c)) and body weight (BW) changes associated with tirzepatide in GADA-positive vs GADA-negative participants with a clinical T2D diagnosis. Methods: Post hoc analyses based on pooled data from SURPASS 2-5, using mixed-model repeated measures from the efficacy analysis set, adjusting for study and baseline covariates including age, sex, baseline values, body mass index (BMI), and GADA status, were conducted on 3791 individuals. Intervention included tirzepatide (5, 10, 15 mg). Main outcome measure included change from baseline in HbA(1c) at weeks 40 (SURPASS-2, -3, -5) and 42 (SURPASS-4) by GADA status. Results: In participants with confirmed GADA status, 3671 (96.8%) were GADA negative and 120 (3.2%) were GADA positive (76 [63.3%] with low and 44 [36.7%] with high GADA levels). Baseline characteristics were similar between groups, except for slightly lower BMI in GADA-positive vs GADA-negative participants (mean [SD] BMI 32.2 [6.1] vs 33.6 [6.3]). At week 40/42, both groups achieved robust reductions in HbA(1c) (-2.11% vs -2.32%) and BW (-9.2 kg vs -9.6 kg) (P < .001, both groups). HbA(1c) reductions were greater in GADA-negative participants (estimated difference [95% CI]: 0.21% [0.03, 0.39]; P = .024) and BW reductions did not differ between groups (0.38 kg [-0.99, 1.75]; P = .588). Conclusion: In this post hoc analysis, tirzepatide was associated with substantial reductions in HbA(1c) and BW irrespective of GADA status in adults diagnosed with T2D, suggesting that tirzepatide may improve glycemic control in individuals with LADA.