Effect of Incretin-Based Weight Loss Drugs on Testosterone Concentrations in Men.

OBJECTIVE

Obesity is associated with a lowering of testosterone concentrations, which improve following weight loss. Incretin-analogs induce substantial weight reduction, yet their effects on testosterone concentrations have not been well characterized. We evaluated changes in total and free testosterone in men treated with the incretin analogs.

METHODS

We conducted a retrospective study of men aged 18 to 89 years from 2021 to 2024. Data were extracted from electronic health records. Two hundred and fifteen patients had total testosterone measured before and during incretin therapy; 61 had paired free testosterone measurements. Men receiving androgen-related therapies were excluded.

RESULTS

The mean age was 55 ± 11 (standard deviation) years, body mass index was 36.3 ± 7.1 kg/m2, 77% had type 2 diabetes. Incretin therapy resulted in a 5% weight loss and reduction in hemoglobin A1c (-0.7 ± 1.6%, P < .001). Total testosterone increased from 332 ± 134 to 399 ± 152 ng/dL (P < .001), and free testosterone increased from by 6.9 ± 3.0 to 8.0 ± 4.2 ng/dL, P = .006. Changes in weight correlated with changes in total (r = -0.28, P < .001) and free testosterone (r = -0.26, P = .04). During incretin therapy, the percentage of patients with normal total testosterone increased from 67% to 86%, P < .001).

CONCLUSIONS

Incretin-based therapies were associated with increases in total and free testosterone, with the largest gains seen in those with greatest weight loss. These findings support a role for incretins in reversing obesity-related low testosterone, potentially reducing the need for exogenous testosterone therapy.