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Peripheral Artery Disease Management / Diabetes Treatment and Management · Journal article
Foot & Ankle Specialist · August 17, 2026
Encouraging direction, but not yet definitive.
This retrospective cohort study found that GLP-1 use was associated with reduced risk of ankle joint injection and total ankle arthroplasty in obese patients, but paradoxically increased risk of arthroscopy in diabetic patients, despite both groups achieving greater weight loss. The conflicting direction of effect between cohorts and inability to explain the mechanism raises questions about confounding and generalizability.
Retrospective cohort study with propensity-matched comparison groups. Adults aged 18+ with obesity (BMI ≥30 kg/m²) or type 2 diabetes (ICD-10: E11) with data in TriNetX Analytics Network, identified between 2016 and 2020.. Intervention: GLP-1 receptor agonist therapy (semaglutide, liraglutide, dulaglutide, exenatide, or lixisenatide), defined as ≥2 prescriptions separated by ≥6 months.. Compared with: No GLP-1 use (matched non-users). TriNetX Analytics Network (US-based multi-centre health data network); specific number of sites not stated..
In obese cohort, GLP-1 users had lower risk of ankle joint injection (HR = 0.8, 95% CI = 0.6–0.9) and TAA (HR = 0.5, 95% CI = 0.3–0.9) In diabetic cohort, GLP-1 use associated with increased risk of arthroscopy (HR = 1.9, 95% CI = 1.2–3.2) but not joint injection or TAA Over 5 years, obese GLP-1 users achieved greater BMI reduction (−2.7 vs −1.6 kg/m²) compared with non-users; diabetic cohort (−2.1 vs −1.7 kg/m²); both P <.01
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These findings are not yet actionable for clinical practice. The opposing effects in obese versus diabetic patients, combined with the counterintuitive finding of greater metabolic improvement not translating uniformly to fewer procedures, suggest either confounding by indication, differences in clinical decision-making between groups, or unmeasured factors affecting both GLP-1 use and ankle procedures. Prospective studies with controlled indications and imaging endpoints are needed.
Retrospective cohort study with propensity matching in a large registry showing differential effects of GLP-1 use on ankle OA interventions by metabolic phenotype, but limited by observational design, inability to control unmeasured confounding, and lack of mechanistic explanation for conflicting outcomes between cohorts.
As stated by the source record.
Quoted from the source exactly as published.
These findings are not yet actionable for clinical practice. The opposing effects in obese versus diabetic patients, combined with the counterintuitive finding of greater metabolic improvement not translating uniformly to fewer procedures, suggest either confounding by indication, differences in clinical decision-making between groups, or unmeasured factors affecting both GLP-1 use and ankle procedures. Prospective studies with controlled indications and imaging endpoints are needed.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Background Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for the treatment of obesity and type 2 diabetes mellitus (T2DM), with established metabolic benefits. However, their influence on musculoskeletal outcomes, particularly in patients with ankle osteoarthritis (OA), remains unclear. Methods We conducted a retrospective cohort study using the TriNetX Analytics Network to evaluate the association between GLP-1 therapy and surgical or nonsurgical interventions for ankle OA. Adults with obesity (body mass index [BMI] ≥30 kg/m 2 ) or T2DM (ICD-10: E11) were identified between 2016 and 2020. Patients were stratified by GLP-1 use, defined as ≥2 prescriptions separated by ≥6 months for semaglutide, liraglutide, dulaglutide, exenatide, or lixisenatide. Outcomes included ankle joint injection (CPT: 20605, 20606), ankle arthroscopy/debridement (CPT: 29891, 29898, 29897, 29895), and total ankle arthroplasty (TAA) or arthrodesis (CPT: 27700, 27702, 27870, 29899). Outcomes were analyzed beginning 6 months after index date. Hazard ratios (HRs) were estimated with 95% confidence intervals (CIs). Results After matching, 3089 obese and 8117 diabetic patients were included in each comparison group. In the obese cohort, GLP-1 users had a lower risk of ankle joint injection (HR = 0.8, 95% CI = 0.6-0.9) and TAA (HR = 0.5, 95% CI = 0.3-0.9), while risk of arthroscopy was not significantly different. In the diabetic cohort, GLP-1 use was associated with increased risk of arthroscopy (HR = 1.9, 95% CI = 1.2-3.2) but not joint injection or TAA. Over 5 years, GLP-1 users achieved greater reductions in BMI compared with non-users (obese cohort: −2.7 vs −1.6 kg/m 2; diabetic cohort: −2.1 vs −1.7 kg/m 2; both P <.01). HbA1c improved significantly in both diabetic groups, with slightly greater reduction in non-users (−6.0% vs −5.5%, P <.01) Conclusion Obese GLP-1 users demonstrated lower rates of invasive ankle procedures, while diabetic GLP-1 users experienced higher arthroscopy utilization. These findings suggest that metabolic improvements may not uniformly translate to musculoskeletal benefit, warranting further investigation. Level of Evidence: III
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