Comparative effects of metformin and pioglitazone on YKL-40 in type 2 diabetes: a randomized clinical trial

Metformin and pioglitazone are believed to exert their long-term benefits by means of amelioration of chronic low-grade inflammation, a key event in development of diabetes and its long-term complications. The present trial was designed to investigate the comparative efficacy of the two anti-diabetes medications on serum concentrations of YKL-40, a novel marker of inflammation.

In a parallel-group, open-label, randomized trial setting (ClinicalTrials.gov Identifier No. NCT01521624), 84 newly diagnosed, medication-naïve type 2 diabetes patients were assigned to metformin 1,000 mg daily (n = 42) or pioglitazone 30 mg daily (n = 42). Serum concentrations of YKL-40, along with highly sensitive C-reactive protein, indices of glycemic control and lipid profile were measured at baseline and after 3 months.

In the analyzed sample (metformin = 40, pioglitazone = 42), both medications were equally effective with regard to control of hyperglycemia, and hsCRP reduction (p > 0.05). However, metformin caused a significant decline in weight (p = 0.005), BMI (p = 0.004), and total cholesterol levels (p = 0.028) of the patients. Metformin also significantly reduced YKL-40 concentrations after 3 months (1.90 ± 17 vs. 1.66 ± 0.15 µg/L, p = 0.019). The amount of change in the pioglitazone arm did not reach statistical significance (2.18 ± 0.14 vs. 2.25 ± 0.16 µg/L, p = 0.687). When compared, metformin was significantly more effective than pioglitazone with respect to YKL-40 reduction in both univariate (p = 0.020, effect size = 6.7%) and multivariate models (p = 0.047, effect size = 5.7%).

Metformin is more effective in reduction of YKL-40 concentration in short term and the effect seems to be independent of degree of glycemic control, or hsCRP reduction.