Can semaglutide (glucagon-like peptide-1 receptor agonist) be initiated in an obese patient with impaired renal function requiring weight reduction for knee replacement?

Can Semaglutide Be Started in an Obese Patient Requiring Weight Reduction for Knee Replacement?

Yes, semaglutide should be initiated in this patient, as it provides substantial weight loss that directly improves knee osteoarthritis pain and function, making it an ideal preoperative intervention for patients requiring weight reduction before knee replacement. 1

Evidence for Semaglutide in Knee Osteoarthritis

The STEP 9 trial specifically demonstrated that semaglutide 2.4 mg weekly in patients with obesity and moderate knee osteoarthritis resulted in 13.7% weight loss at 68 weeks (versus 3.2% with placebo), with a 41.7-point reduction in WOMAC pain scores compared to 27.5 points with placebo. 1 This trial directly addresses your clinical scenario, showing that semaglutide not only achieves the weight loss needed for surgical candidacy but also improves the underlying knee pain and physical function that necessitates the replacement. 1

The physical function improvements are clinically meaningful, with SF-36 physical function scores improving by 12.0 points versus 6.5 points with placebo. 1 This suggests patients may experience symptom relief during the weight loss period, potentially allowing some to defer or avoid surgery altogether.

Dosing and Administration Protocol

Start semaglutide at 0.25 mg subcutaneously weekly for 4 weeks, then escalate to 0.5 mg for 4 weeks, 1.0 mg for 4 weeks, 1.7 mg for 4 weeks, and finally reach the maintenance dose of 2.4 mg weekly after 16 weeks of titration. 2 This gradual titration minimizes gastrointestinal side effects, which are the primary reason for discontinuation (6.7% in clinical trials). 1

The medication should be combined with counseling on physical activity and a reduced-calorie diet, as this combination approach was used in the successful STEP trials. 3, 1

Special Consideration: Renal Function

Since the expanded question mentions impaired renal function, this is actually not a contraindication to semaglutide use. 4

Renal impairment does not impact semaglutide pharmacokinetics in a clinically relevant manner, including in patients with severe renal impairment (eGFR 15-29 mL/min/1.73 m²) and end-stage renal disease on dialysis. 4, 5 A retrospective study of 76 patients with advanced CKD (stage 4 or greater, including dialysis patients) showed that semaglutide was tolerated by 63.1% of patients with no adverse effects, achieved 4.6% weight loss, and improved glycemic control. 5

Two case reports demonstrated successful use of semaglutide in non-diabetic ESKD patients on hemodialysis, achieving 16% and 12.6% weight loss in under 9 months to meet BMI targets for renal transplant waitlisting. 6 This proves the concept works even in the most severe renal impairment scenarios.

For patients with type 2 diabetes and chronic kidney disease, semaglutide provides additional kidney-protective benefits, reducing major kidney disease events by 24% and slowing eGFR decline. 7

Critical Perioperative Safety Concern

The most important caveat is the aspiration risk during anesthesia. Multiple case reports document regurgitation and pulmonary aspiration in patients on GLP-1 receptor agonists despite extended fasting periods (up to 20 hours for solids). 3 This occurs because semaglutide delays gastric emptying, a core mechanism of its weight loss effect. 4

Practical management strategy:

• Inform the surgical team early that the patient is on semaglutide 3
• Consider discontinuing semaglutide 10-14 days before elective knee replacement surgery, though even this may not eliminate retained gastric contents 3
• The anesthesia team should plan for rapid sequence intubation or other aspiration precautions 3
• Studies show 24.2% of semaglutide patients had increased residual gastric content at endoscopy despite 10-14 day discontinuation and extended fasting 3

Contraindications to Screen For

Absolute contraindications include: 3, 2

• Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2)
• Pregnancy or breastfeeding

Use with caution in patients with: 3, 2

• History of pancreatitis (monitor closely but not an absolute contraindication)
• History of cholelithiasis (increased risk of acute gallbladder disease)

Expected Timeline and Monitoring

Patients should achieve clinically meaningful weight loss (≥5%) by 16 weeks on the maintenance dose. 3 Real-world data shows mean weight loss of 13.4% at 6 months, 17.6% at 12 months, and 20.4% at 24 months when combined with the WeGoTogether support program. 8

Monitor for:

• Gastrointestinal symptoms (nausea, vomiting, diarrhea) especially during dose escalation 3, 2
• Signs of pancreatitis (severe abdominal pain) 3, 2
• Gallbladder symptoms 3, 2
• Blood pressure changes (may need to reduce antihypertensive medications as weight decreases) 2

Bottom Line Algorithm

1. Screen for contraindications (MEN2, medullary thyroid cancer history, pregnancy) 3, 2
2. Initiate semaglutide 0.25 mg weekly with lifestyle counseling 2, 1
3. Titrate monthly to 2.4 mg over 16 weeks 2
4. Continue treatment for 6-12 months to achieve target weight for surgery 1, 8
5. Coordinate with surgery team at least 2-3 weeks before planned knee replacement to discuss discontinuation timing and aspiration precautions 3
6. Renal impairment is not a barrier to treatment, even in advanced CKD or dialysis 4, 5, 6

The evidence strongly supports this approach, with the STEP 9 trial providing direct evidence in your exact patient population. 1