Association of semaglutide use with outcomes in chronic plantar heel pain: a prospective observational cohort and a pilot interventional study.

BACKGROUND: Whether patients with chronic plantar heel pain (PHP) can benefit from glucagon-like peptide-1 receptor agonists (GLP1-RAs) remained unclear. METHODS: This study included a prospective observational cohort and a pilot interventional component. In the observational arm, more than 3000 adults with chronic PHP (duration of symptoms >6 months) were recruited with at least 2-year follow-up from two medical centers. The primary endpoint was the change from baseline of Foot Health Status Questionnaire (FHSQ) pain subdomain at the last follow-up. Secondary endpoints included first-step pain, FHSQ function subdomain, the amount of NSAIDs consumption, number of injection therapies/extracorporeal shockwave therapy (ESWT) sessions/manual stretching, days of orthosis wearing and thickness of plantar fascia. As supporting evidence, a pilot interventional study was conducted in 30 patients with chronic PHP who received semaglutide, with outcomes assessed over 12 months using before-and-after evaluations of pain, function, and imaging. RESULTS: In the prospective observational cohort, 92 out of 2902 patients who received semaglutide in purpose of treating type 2 diabetes (T2DM) and/or weight loss in the final analysis were identified. Change from baseline in FHSQ pain subdomain was significantly higher in semaglutide group compared with control group (adjusted mean difference, 14.86 [95% CI, 9.97 to 19.75], P < 0.001), favoring semaglutide. Similar results were observed from the analysis of FHSQ function subdomain, first-step pain and several therapeutic interventions (oral and topical NSAIDs, corticosteroid injection and orthosis wearing). For structural alterations, plantar fascia thickening velocity was significantly lower in the semaglutide group when compared with control group (-0.25 mm/year [-0.41 to -0.09], P = 0.002). For interventional use of semaglutide, improvements in all measured outcomes (FHSQ pain/function subscales, first-step pain and thickness of plantar fascia) were observed with all P values less than 0.001. In the interventional substudy, mean FHSQ pain scores improved from 28.09 ± 10.34 at baseline to 60.28 ± 21.34 at follow-up ( P < 0.001). FHSQ function subdomain scores increased from 27.23 ± 17.44 to 80.71 ± 19.55 ( P < 0.001). CONCLUSIONS: Semaglutide might be a potential therapeutic candidate for chronic PHP patients by improving patient-reported outcomes and plantar fascia thickening. Further randomized trial is warranted by our study to further evaluate the therapeutic effects of GLP-1RAs on chronic PHP.