Elucidating the role of weight loss and glycaemic control in patients with type 2 diabetes

Abstract

AbstractAimsTo investigate the independent contributions of glycated haemoglobin (HbA1c) reduction and weight loss to clinical outcomes in patients with type 2 diabetes (T2D) treated with antidiabetic drugs, including glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs).Materials and MethodsThis observational, retrospective cohort study used deidentified electronic health record‐derived data from patients evaluated at the Cleveland Clinic (1 January 2000–31 December 2020). Cohort A included 8876 patients with newly diagnosed T2D treated with any of six antidiabetic drug classes. Cohort B included 4161 patients with T2D initiating GLP‐1RA treatment. The effects of body mass index (BMI) and HbA1c reduction, variability, and durability on clinical outcomes were investigated.ResultsIn Cohort A, each 1% BMI reduction was associated with 3%, 1%, and 4% reduced risk of heart failure (p = 0.017), hypertension (p = 0.006), and insulin initiation (p = 0.001), respectively. Each 1% (~11 mmol/mol) HbA1c reduction was associated with 4% and 29% reduced risk of hypertension (p = 0.041) and insulin initiation (p = 0.001), respectively. In Cohort B, each 1% BMI reduction was associated with 4% and 3% reduced risk of cardiovascular disease (p = 0.008) and insulin initiation (p = 0.002), respectively. Each 1% (~11 mmol/mol) HbA1c reduction was associated with 4% and 16% reduced risk of chronic kidney disease (p = 0.014) and insulin initiation (p = 1 × 10−4), respectively. Lower BMI variability and greater BMI durability were associated with decreased risk of clinical outcomes in both cohorts.ConclusionsAntidiabetic medication‐associated, and specifically GLP‐1RA‐associated, weight loss and HbA1c reductions independently reduce real‐world clinical outcome risk.