Aims/IntroductionChemerin, a novel member of the family of adipocytokines, has been shown to be associated with insulin resistance, as well as micro- and macrovascular complications of diabetes. We investigated the effects of pioglitazone and metformin, two commonly prescribed antidiabetic agents, on the reduction of serum chemerin concentrations. Materials and MethodsIn an open-labeled randomized clinical trial, 81 patients with newly diagnosed type2 diabetes who were not taking antidiabetic medications were recruited. Patients were randomly assigned to either pioglitazone 30mg daily or metformin 1,000mg daily. Serum chemerin concentrations, indices of glycemic control, serum lipids concentrations, and anthropometric parameters were measured at baseline and after 3months. ResultsPioglitazone and metformin did not alter waist circumference, weight or body mass index after 3months. In contrast, all indices of glycemia and insulin resistance improved substantially after 3months' treatment with both medications (P<0.01 in all analyses). There was a significant decrease in chemerin concentrations after 3months in the pioglitazone group (P=0.008). Similarly, metformin caused a significant drop in chemerin concentrations at week12 (P=0.015). When compared, metformin and pioglitazone proved to be equally effective in the alleviation of chemerin concentrations (P=0.895, effect size: 0.1%). ConclusionsThe present findings show that pioglitazone and metformin have comparable efficacy on serum chemerin concentrations, albeit through different mechanisms. Future studies need to focus on the clinical implications of lowered chemerin concentration on improvement of diabetes complications. This trial was registered with (no. NCT01593371).