783-P: Efficacy of GLP-1RA according to Type 2 Diabetes Phenotypes-A Monocentric Retrospective Study

• Published in: Diabetes (New York, N.Y.) Vol. 73; p. 1
• Main Authors: Caruso, Irene, Giordano, Fiorella, Di Gioia, Ludovico, Matichecchia, Immacolata I, Cignarelli, Angelo, Sorice, Gian Pio, Perrini, Sebastio, Natalicchio, Annalisa, Laviola, Luigi, Giorgino, Francesco
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01.06.2024
• Subjects: Age; Diabetes; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); Genotype & phenotype; Insulin; Ketoacidosis; Phenotypes
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db24-783-P

Introduction & Objective: Type 2 diabetes (T2D) is considerably heterogeneous due to different pathogenetic mechanisms that may affect response to treatment. We aimed to assess the efficacy of GLP-1RA according to the phenotypes described by Ahlqvist et al. (Diabetes, 2000). Methods: In this retrospective monocentric study, every individual attending our outpatient clinic since 2013 was evaluated for eligibility. Main inclusion criteria were age at T2D diagnosis ≥50 years, T2D duration ≤5 years, BMI ≥25 kg/m2, first users of a GLP-1RA with at least one follow-up visit at 6-12 months. Main exclusion criteria were type 1 diabetes, LADA, ketoacidosis. The assignment to T2D phenotypes (MARD, mild age-related diabetes; MOD, mild obesity-related diabetes; SIDD, severe insulin deficient diabetes; SIRD, severe insulin resistant diabetes) was performed via the algorithm developed by Bello-Chavolla et al. (BMJ, 2020). The primary outcome was difference in HbA1c change from baseline, evaluated with ANOVA. SHapley Additive exPlanations (SHAP) allowed to rank predictors of HbA1c reduction. Kaplan-Meier analysis and log-rank test were used to estimate differences in time to treatment failure, defined as time to HbA1c ≥7.0%. Results: We enrolled 128 patients. The SIDD phenotype was associated with a significantly greater HbA1c reduction (-1.9% vs. -0.67% [MARD], -0.75% [MOD], -0.56% [SIRD]; p<0.001) following GLP-1RA initiation after a median follow-up of 8 months. However, SHAP analysis identified baseline HbA1c, rather than SIDD phenotype, as the most relevant predictor of HbA1c change, accounting for ~0.5% HbA1c reduction. Yet, belonging to the SIDD phenotype was associated to earlier treatment failure (p<0.01). Conclusion: Easily available clinical variables such as baseline HbA1c might be more useful to predict response to GLP-1RA than T2D subclassification. However, the diverse pathogenesis of T2D phenotypes might account for differences in treatment durability.