Optimization of Obesity for Total Knee Replacement With Glucagon-like Peptide-1 Receptor Agonist

Summary

Studies have shown that obese patients undergoing total knee replacement (TKR) surgery face a higher risk of perioperative issues such as increased use of pain medication, surgical site infections, and the need for revision surgeries compared to non-obese patients. Obesity is also linked to more significant preoperative pain and lingering symptoms post-surgery. Consequently, there's a growing interest in weight loss interventions prior to TKR to enhance perioperative care and outcomes. Recent retrospective studies have indicated that such interventions can improve physical function post-TKR.

Research focusing on weight loss interventions before joint replacement surgery is limited.

There is currently a gap in research regarding RCTs on weight loss interventions using anti-obesity drugs before TKR, particularly in Asian populations.

One promising avenue under exploration involves the use of glucagon-like peptide 1 receptor agonists (GLP-1RAs) as anti-obesity medication before total knee replacement (TKR) surgery. However, there are currently no randomized controlled trials (RCTs) examining the effects of GLP-1RAs on knee arthroplasty outcomes. Large database studies have indicated that GLP-1RAs may decrease the likelihood of certain post-surgery complications but increase the risk of others.

In summary, addressing obesity through weight loss interventions, particularly with GLP-1RAs, holds promise for improving outcomes in TKR patients. However, further research, including randomized controlled trials, is necessary to fully understand the effects of GLP-1RAs on perioperative outcomes and patient health.

Conditions

• Osteoarthritis (OA) of the Knee

Interventions

DRUG

Glucagon-like peptide-1 receptor agonists (GLP 1 RA)

Patients in intervention group will have GLP-1RA semaglutide for 48 weeks and then stops for one month before and after TKR following the latest anesthesia guideline for GLP-1RA. Followed by TKR They will continue semaglutide for 48 weeks during the post-operative follow-up period. This is decided based on balancing treatment effect of semaglutide, waiting time for TKR, and TKR follow-up requirement. In Hong Kong, waiting time for TKR would be \~4 years and so a period of 12 months treatment of semaglutide is reasonable. And in the STEP 6 trial, weight loss at week 52 (-12%) is similar to that in study end at week 68(-13·2%), and STEP5 trial showed maintaining semaglutide to week 104 could maintain weight loss of similar degree as in week 52. And the consensus of assessing TKR Patient-Reported Outcome Measures (PROMs) is one year follow up.

OTHER

Control (Standard treatment)

If patients are randomized to the control group, they will receive routine follow-up with general advice on diet and physical activity but will not receive semaglutide, and will not be offered a specific management program for their weight. This is in line with current practice.

Sponsors & Collaborators

• The University of Hong Kong

  lead OTHER

Principal Investigators

• Lawrence Lau, FRCS, PhD · The University of Hong Kong

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

40 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-09-01

Primary Completion

2027-07-01

Completion

2028-07-01

FDA Drug

Yes