Long-term risk of total joint replacement associated with second-line glucose-lowering therapies in type 2 diabetes: A population-based retrospective cohort study
Authors' conclusion
Among patients with T2DM initiating second-line glucose-lowering therapy, SGLT2i use was associated with more favorable OA-related outcomes, most consistently in comparison with GLP-1 RA.
Study context
- Population
- Adults with T2DM initiating second-line glucose-lowering therapy, background therapy not restricted; TriNetX Global Health Research Network
- Exposure
- Pairwise comparisons of second-line glucose-lowering therapies: SGLT2i vs GLP-1 RA, SGLT2i vs DPP4i, GLP-1 RA vs DPP4i
- Outcome
- Total joint replacement (TJR)
- Follow-up
- 10 years
Methodological detailsnew-user, active-comparator, propensity score-matched pairwise comparisons, population-based
- New-user
- Active-comparator
- Propensity score-matched pairwise comparisons
- Population-based
Main finding
As reported in the abstract
10-year observed risk of TJR (matched cohorts)
Hazard ratio (95% CI)
SGLT2ivs GLP-1 RA
0.85(0.73–1.00)
SGLT2ivs DPP4i
1.10(0.95–1.27)
GLP-1 RAvs DPP4i
1.22(1.07–1.39)
Observational data: associations, not effects.
Secondary outcomes
Overall osteoarthritis (OA)
- SGLT2i associated with lower risks of overall OA than both GLP-1 RA and DPP4i, stronger for knee OA than hip OA
Total joint replacement (TJR) in patients with pre-existing OA (subgroup)
- SGLT2i remained associated with lower TJR risk than GLP-1 RA
Knee- vs hip-related outcomes
- Associations more evident for knee-related than hip-related outcomes
Original publication
Long-term risk of total joint replacement associated with second-line glucose-lowering therapies in type 2 diabetes: A population-based retrospective cohort study. Semin Arthritis Rheum. Published 8 May 2026. doi:10.
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