GLP1 Receptor Agonist and SGLT2 Inhibitor Combination: An Effective Approach in Real-world Clinical Practice

Purpose: The aim of this study was to evaluate the effectiveness and safety of combination therapy with a sodium-glucose cotransporter-2 (SGLT2) inhibitor and a glucagon-like peptide-1 receptor agonist (GLP1RA) in patients with inadequately controlled type 2 diabetes.

Methods: A retrospective search of electronic prescriptions of patients undergoing GLP1RA and SGLT2 inhibitor combination therapy was conducted. Once the patients had been identified, demographic data, blood and urine analyses (glycosylated hemoglobin [HbA_1c], glucose, renal function, albuminuria, lipid profile, liver enzymes, and uric acid), physical examination (weight, body mass index, and blood pressure), and adverse effects were obtained from their electronic clinical records according to each of the following 3 periods: before the initiation of the combination, the first visit after initiation, and the last available visit. The influence of the duration of diabetes and the drug combination sequence on the effectiveness of the treatment was also analyzed. Statistical analysis was performed with SPSS version 21.0 (IBM SPSS Statistics, IBM Corporation, Armonk, New York). Quantitative variables are presented as mean and SD and were compared by using the Student t test, one-way ANOVA, or repeated measures ANOVA with Bonferroni correction. Categorical variables are expressed as percentages and were compared by using the χ² test.

Results: A total of 212 patients were included, with women accounting for 52.4%. The mean age (SD) of the population was 61.5 (9.6) years. A significant reduction in HbA_1c (-12 mmol/mol [-1.1%]) was observed with combined therapy (P < 0.001). The target of HbA_1c <53 mmol/mol (<7%) was achieved in 42% of the participants. Mean weight loss was -3.5 kg, and almost 40% of the patients attained the weight loss goal of ≥5% (P < 0.001 in all analyses). Transaminase levels and renal parameters also improved. These benefits persisted over time and bore no relation to the evolution of diabetes. Simultaneous initiation of a combination of a GLP1RA and SGLT2 inhibitor led to faster weight loss and a greater decrease in HbA_1c than when they are used sequentially; however, the long-term benefits in terms of metabolic control were similar. Adverse events were rare, and a tendency for a reduced insulin dose was observed.

Implications: The findings of this study reveal the combined benefits of a GLP1RA and SGLT2 inhibitor in real-world clinical practice. In general, the combined treatment was well tolerated, and few adverse events were detected.