Clinical and Metabolic Effects of Incretin-Based Pharmacotherapy in Normal-Weight Patients With Type 2 Diabetes: A Real-World Analysis.

Purpose To evaluate the impact of incretin-based pharmacotherapy on clinical outcomes in normal to underweight patients with type 2 diabetes mellitus in a real-world setting. Methods Patients with a body mass index less than 25 kg/m2 prescribed a glucagon-like peptide-1 receptor agonist or glucagon-like peptide-1 receptor agonist/glucose-dependent insulinotropic polypeptide receptor agonist for type 2 diabetes mellitus within a single health system were included in this analysis. The primary objective is a change in hemoglobin A1c from baseline to at least three months after an optimally tolerated incretin-based pharmacotherapeutic agent dose. Key secondary objectives include the absolute change in weight, low-density lipoprotein (LDL) levels, and systolic blood pressure from baseline to optimization, as well as the absolute change in the number of diabetes, hypertension, and cholesterol medications. Additionally, the number of patients who meet the categorization as underweight from baseline to optimization will be assessed. Results Within the health system described, 100 patients out of the 7942 prescribed an incretin-based pharmacotherapeutic agent within the two-year timeframe met inclusion criteria. Of these, 45 were on the medication for at least six months and had complete post-optimization records and so were included in the analysis. Within this population, the average baseline hemoglobin A1c was 8.83%, and after dose optimization, it was 7.98%. The average hemoglobin A1c change was -0.84% (P = 0.008) from baseline to optimization. The average baseline weight in the population analyzed was 64.3 kg, and after dose optimization, it was 62.7 kg. The average change in weight after optimization was -1.61 kg (P = 0.01), and the average change in body mass index after optimization was -0.45 kg/m2 (P = 0.38). The average changes in LDL and systolic blood pressure after optimization were -10 mg/dL (P = 0.02) and -4 mmHg (P = 0.28), respectively. Conclusion An observation of significantly improved hemoglobin A1c was seen in this real-world analysis of normal-weight patients with type 2 diabetes mellitus prescribed incretin-based pharmacotherapy. Weight loss was modest, and the change in body mass index was not statistically significant. These findings suggest that incretin-based pharmacotherapy is effective in improving glycemic control in this population with modest weight reduction. Further studies are needed to explore the long-term efficacy and safety of incretin-based pharmacotherapy in normal and underweight individuals with type 2 diabetes mellitus.