Summary Men with type 2 diabetes (T2D) and obesity are often characterised by low testosterone (T). We aimed to determine whether exenatide (EXE) combined metformin (MET) treatment has a better effect on serum total testosterone (TT) levels than glimepiride (GLI) combined MET treatment in men with T2D and obesity. In a multicentre, 12‐week observational study, 176 obese T2D men with failed glycaemic control were included in the study: ninety men (mean age, 43.00 ± 8.50 years) in EXE + MET group and 86 men (mean age, 44.00 ± 7.00 years) in GLI + MET group. Serum TT levels were more significantly increased in EXE + MET group than GLI + MET group (121.72 ± 56.73 ng/dl versus 34.67 ± 16.30 ng/dl). The increasement of TT levels in those patients who lost body weight ≥5% was significantly greater than those who lost weight <5% in the two groups. The changes in TT levels are closely related to the changes in waist circumference (r = −.443, p < .001). Sexual function assessment of EXE + MET group was more significantly improved than GLI + MET group (p < .001). No serious adverse events were observed. In conclusion, short‐term combined treatment with EXE and MET is superior to GLI combined MET treatment in the improvement of serum TT levels, which could lead to an improvement of sexual hypofunction in patients with obesity and T2D.