Effects of empagliflozin, sitagliptin and metformin on omentin 1 and resistin in patients with obesity and type 2 diabetes, a prospective study

Type 2 diabetes mellitus and obesity are characterized by a persistent, low‑grade inflammatory state that impairs the normal balance of adipokine activity. Among these adipokines, omentin‑1, which elicits anti‑inflammatory effects, and resistin stimulate inflammation due to their correlation with the accumulation of visceral fat, insulin resistance and various cardiometabolic disorders. However, how the effects of conventional therapy on these adipokines differ in patients who have not previously received treatment remains uncertain. Therefore, this study evaluated the effects of three treatment groups on circulating adipokine levels in patients with type 2 diabetes. This 12-week, prospective, open-label, parallel-group study included 144 treatments-naive adults with newly diagnosed T2DM who were allocated to empagliflozin–metformin ( n = 50), sitagliptin–metformin ( n = 50) and metformin monotherapy ( n = 44). Circulating omentin-1 and resistin levels were evaluated at baseline and after 12 weeks using ELISA, and the level of glycated haemoglobin (HbA1c) was assessed on an automated analyser (cobas c 111). Additional outcomes included fasting blood glucose levels and routine anthropometric measures. As the adipokine values were nonnormally distributed, Wilcoxon signed-rank and Kruskal–Wallis tests were used. Participants in all groups were middle-aged (mean 50–54 years) who were uniformly overweight or obese. Empagliflozin–metformin produced a substantial increase in omentin-1 (mean change 31.10 ng/mL; p = 0.009) accompanied by a pronounced reduction in resistin (mean change 0.54 ng/mL; p < 0.001). Sitagliptin–metformin was correlated with a marked decrease in omentin-1 ( p < 0.001) without a significant change in resistin ( p = 0.923). Metformin resulted in significant decreases in both omentin-1 ( p = 0.008) and resistin ( p = 0.004). At week 12, compared with the other interventions, empagliflozin–metformin resulted in elevated omentin-1 levels and decreased resistin levels ( p = 0.009 and p < 0.001), whereas the glycaemic and anthropometric indices of all treatment groups improved (< 0.001). Among the study participants, empagliflozin combined with metformin led to a distinctly more favourable adipokine pattern than the other regimens did, characterized by an increase in omentin-1 and a reduction in resistin, while achieving gains in glycaemic control and anthropometric measures. This profile supports the potential early benefit of adding an SGLT2 inhibitor to metformin on adipokine balance and inflammatory processes beyond glucose lowering. Trial registration: ClinicalTrials.gov NCT07531108.