Metabolic dysfunction in Type 2 diabetes mellitus (T2DM) extends beyond hyperglycemia and includes inflammatory and vascular abnormalities. Adropin has emerged as a potential biomarker linked to insulin resistance and metabolic regulation. A randomized clinical trial published in BMC Endocrine Disorders compared the metabolic effects of empagliflozin and sitagliptin added to metformin therapy in adults with inadequately controlled T2DM.

This single-center, open-label, parallel-group superiority trial enrolled 100 adults with glycated hemoglobin (HbA1c) ≥7.5% despite stable metformin therapy. Participants were randomized to empagliflozin 10 mg once daily or sitagliptin 100 mg once daily for 12 weeks. The co-primary outcomes were changes in circulating adropin levels and insulin resistance measured by homeostasis model assessment of insulin resistance (HOMA-IR).

Findings

• Serum adropin levels increased in both treatment groups, rising from 291±133 to 362±124 pg/mL with empagliflozin and from 299±98 to 358±126 pg/mL with sitagliptin (time effect: F=19.67; P<0.001).
• HOMA-IR declined from 10.08±4.44 to 6.65±2.50 with empagliflozin and from 9.28±2.97 to 7.15±1.80 with sitagliptin (interaction: F=4.85; P=0.032).
• HbA1c decreased from 8.10±0.53 to 7.04±1.18 with empagliflozin and from 8.29±0.66 to 7.62±0.68 with sitagliptin (interaction: F=4.30; P=0.043).
• Empagliflozin produced greater reductions in fasting insulin and triglycerides and a larger increase in high-density lipoprotein cholesterol (HDL-C) compared with sitagliptin.
• Tumor necrosis factor-α levels declined in both treatment groups, and no serious adverse events were reported.

The findings suggested that both empagliflozin and sitagliptin improved metabolic and inflammatory markers in adults with T2DM. However, empagliflozin produced broader metabolic benefits, particularly for insulin resistance, glycemic control, and lipid parameters.