Effects of semaglutide in patients with chronic ankle instability: evidence from a prospective cohort.

BACKGROUND: Whether patients with chronic ankle instability (CAI) can benefit from weight loss yielded by using glucagon-like peptide-1 receptor agonists (GLP1-RAs) has remained unclear. METHODS: In this observational study, we recruited more than 2000 adults with CAI according to the selection criteria proposed by International Ankle Consortium with at least two-year follow up from three medical centers. The primary endpoint was the change from baseline of the Foot and Ankle Ability Measure (FAAM) sports subscale at the last follow up. Secondary endpoints included the change from baseline of Foot and Ankle Outcome Score (FAOS)/ Cumberland Ankle Instability Tool (CAIT)/ FAAM activities of daily living (ADL) subscale, number of ankle sprains during study period, incident ankle surgery in treatment of CAI. RESULTS: In this study, 71 out of 2018 patients who received semaglutide in purpose of treating type 2 diabetes (T2DM) and/or weight loss during the study period. After controlling baseline characteristics, the adjusted mean difference in change from baseline was 16.3 for FAAM sports subscale and 9.3 for FAAM ADL subscale. Likewise, the adjusted analysis of five subscales of FAOS showed similar results, all consistently favoring semaglutide group. For CAIT, patients in the semaglutide group had achieved statistically significant improvement compared with control group. The association of semaglutide exposure with improvement in FAAM sports and ADL subscales was mediated by the weight loss measured by BMI (mediation proportion: FAAM sports subscale, 31.2% [22.2-41.2%]; FHSQ ADL subscale, 34.1% [24.4-44.8%]). We also observed statistically significant decreases in number of recurrent ankle sprains during study period. For incident ankle surgery, 1 out of 71 patients (1.4%) and 151 out of 1947 patients (7.8%) received ankle surgeries in semaglutide and control groups, respectively (P = 0.047). CONCLUSIONS: Semaglutide may show potential benefits as a supplementary intervention in treatment of CAI by improving patient-reported outcomes and preventing recurrent ankle sprains. Further randomized trial is warranted by the current study to further confirm our findings. TRIAL REGISTRATION: researchregistry10716.