The GLP-1 receptor agonist exenatide reduces serum TSH by its effect on body weight in people with type 2 diabetes.

OBJECTIVE: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in patients with type 2 diabetes and obesity leads to a significant reduction in serum thyrotropin (TSH) levels but it is unclear whether this is related to weight loss and improvement in sensitivity to thyroid hormones (TH). DESIGN, PATIENTS AND MEASUREMENTS: We prospectively analysed clinical and biochemical data in patients with type 2 diabetes and obesity who were commenced on the GLP-1 RA exenatide and followed them for 12 months. We assessed the relationship between changes in body weight and serum TSH and resistance to TH indices. RESULTS: In 112 patients (mean age: 53.5 years, 43.8% female, mean body mass index: 39.8 kg/m ), 12 months of exenatide treatment was associated with a mean (95% CI) percent body weight loss of 6.5% (5.0%-8.1%) and change in serum TSH of -0.25 mU/L (-0.43 to -0.06). There was a significant negative and nonlinear relationship between change in serum TSH and percent body weight loss: -0.25 mU/L with 5%, -0.4 mU/L with 10% and -0.5 mU/L with 15%, respectively, whereas a rise in serum TSH of 0.5 mU/L was associated with 5% weight gain. There were no changes observed in serum FT4 levels with weight loss but a significant reduction in resistance to TH indices was noted. CONCLUSIONS: Exenatide therapy reduces serum TSH levels and improves central sensitivity to TH action over 12 months via its effect on weight loss. The effectiveness of weight loss strategies, rather than TH replacement, should be investigated in individuals with obesity and mildly raised serum TSH levels.