SGLT2 inhibitors reduce osteoarthritis and joint replacement risk more than GLP-1 drugs in 75,000 diabetics | Research

The takeaway

In 75,352 propensity-matched T2DM patients, SGLT2 inhibitors reduced new-onset osteoarthritis risk by 4.9% (HR 0.951) and joint replacement risk by 29.7% (HR 0.703) compared to GLP-1 receptor agonists.

30% fewer joint replacements
SGLT2 inhibitors reduced joint replacement surgery risk by 30% compared to GLP-1 drugs in 75,352 matched diabetic patients

What the researchers found

SGLT2i vs GLP-1RA: OA HR 0.951 (95% CI 0.916-0.988); joint replacement HR 0.703 (95% CI 0.550-0.898). 37,676 matched per group. Mean age 59.5. TriNetX platform (131M patients).

Why it matters

Osteoarthritis affects millions and has no disease-modifying drug. If SGLT2 inhibitors truly reduce OA risk, they could become the first pharmacological agents with joint-protective properties.

How the study worked

Propensity score-matched retrospective cohort from TriNetX Global Collaborative Network (131M patients, 109 organizations). 51,177 SGLT2i and 52,977 GLP-1RA users matched to 37,676 per group.

What this study cannot tell us

Retrospective observational. GLP-1 users may have higher BMI (more OA risk). Joint replacement as outcome may reflect referral patterns. Cannot determine mechanism.

How to read the evidence

Large propensity-matched cohort from a 131M-patient network. Strong observational evidence.

When this study was published

Published in 2025.

The bigger picture

SGLT2 inhibitors continue to show benefits beyond glucose control. Their anti-inflammatory properties may protect joints—adding musculoskeletal health to their growing list of organ-protective effects.

Questions still open

Is the OA protection from SGLT2 anti-inflammatory effects or weight/metabolic improvement?
Should T2DM patients with OA preferentially receive SGLT2i?
Would prospective OA trials with SGLT2i confirm these findings?

Common questions

Can diabetes drugs protect your joints?

This large study found SGLT2 inhibitors (like empagliflozin and dapagliflozin) reduced the risk of developing osteoarthritis by about 5% and joint replacement surgery by 30% compared to GLP-1 drugs. The anti-inflammatory properties of SGLT2 inhibitors may explain this joint-protective effect.

Should I choose SGLT2 inhibitors over GLP-1 drugs if I have joint problems?

If you have type 2 diabetes and osteoarthritis or joint concerns, this data suggests SGLT2 inhibitors may provide additional joint protection. However, GLP-1 drugs have advantages for weight loss and cardiovascular protection. Discuss the trade-offs with your doctor based on your specific health priorities.

Read the original research

Comparison of Sodium-Glucose Cotransporter 2 Inhibitors Versus Glucagon-Like Peptide-1 Receptor Agonists and Risks of Osteoarthritis and Arthroplasty in Patients With Type 2 Diabetes Mellitus: A Propensity Score-Matched Cohorts Retrospective Study.

Diabetes/metabolism research and reviews, 41(5), e70051

View on PubMed ↗Publisher’s paper ↗

Citation

Su, Yu-Chi; Hsieh, Pei-Chun; Lai, Edward Chia-Cheng; Lin, Yu-Ching. (2025). Comparison of Sodium-Glucose Cotransporter 2 Inhibitors Versus Glucagon-Like Peptide-1 Receptor Agonists and Risks of Osteoarthritis and Arthroplasty in Patients With Type 2 Diabetes Mellitus: A Propensity Score-Matched Cohorts Retrospective Study.. Diabetes/metabolism research and reviews, 41(5), e70051. https://doi.org/10.1002/dmrr.70051