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ForumsPharmacology & MechanismsSemaglutide fatty acid sidechain — 12 month update

Semaglutide fatty acid sidechain — 12 month update

SaraMom3 Wed, Sep 11, 2024 at 3:09 PM 36 replies 2,367 viewsPage 1 of 8
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SaraMom3
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Aug 2024
Ohio
Sep 11, 2024 at 3:09 PM#1
I want to raise a clinical concern that's increasingly relevant as more surgical patients are on GLP-1 RAs: wound healing. I've noticed a pattern in my abdominoplasty patients who are on semaglutide. In the past year, I've performed 23 abdominoplasties in patients who were on or recently discontinued semaglutide (within 3 months). Compared to my historical complication rates: - Wound dehiscence: 17% vs my usual 4% - Seroma: 26% vs my usual 12% - Delayed primary healing (>21 days to full closure): 22% vs my usual 8% This is NOT published data — it's my personal case series and I acknowledge all the biases. These patients also lost significant weight rapidly, may have nutritional deficiencies, and had more redundant tissue (hence the abdominoplasty). Confounders abound. But I'm not the only one seeing this. The ASPS and ASAPS have both issued advisories (2025) recommending GLP-1 RA discontinuation 2-4 weeks before elective surgery, primarily citing aspiration risk from delayed gastric emptying. Wound healing is mentioned as a secondary concern. What's the mechanism? Is this real or am I pattern-matching?
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LeilaHI
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Jan 2025
Honolulu, HI
Sep 11, 2024 at 5:36 PM#2
I work in a wound care center and I've been tracking this informally. Over the past 18 months, I've seen an increase in post-surgical wound complications in patients on GLP-1 RAs, particularly after bariatric surgery conversions (patients who switch from GLP-1 RA to surgical management), body contouring procedures, and large joint arthroplasties. Potential mechanisms I've been considering: 1. Caloric deficit: Many patients on GLP-1 RAs are in profound caloric deficit. Guo & DiPietro (J Dent Res, 2010) showed that caloric restriction impairs all phases of wound healing — inflammation, proliferation, and remodeling. Protein-calorie malnutrition reduces collagen synthesis, angiogenesis, and immune cell function at the wound site. 2. Protein/amino acid deficiency: Collagen synthesis requires proline and lysine (plus vitamin C as a cofactor). If protein intake is inadequate (common on GLP-1 RAs as we discussed in the MPS thread), collagen deposition will be impaired. 3. Micronutrient deficiencies: Zinc, vitamin A, and vitamin C are critical for wound healing. Rapid weight loss can deplete these. I've seen several patients with zinc levels <60 μg/dL (normal >70) who were on semaglutide. 4. Direct GLP-1R effects: GLP-1 receptors are expressed on macrophages, fibroblasts, and endothelial cells — all key players in wound healing. Whether GLP-1 RA therapy alters their function is largely unstudied.
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PeptideSynthNJ
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234
1,234
Aug 2024
Princeton, NJ
Sep 11, 2024 at 8:03 PM#3
From the anesthesia perspective, the more immediate surgical concern is aspiration risk. The ASA (American Society of Anesthesiologists) released updated guidance in June 2025: - Semaglutide/dulaglutide (weekly formulations): Hold for 3 weeks before elective surgery - Liraglutide/exenatide (daily formulations): Hold for 1 week - Tirzepatide: Hold for 3 weeks - All GLP-1 RAs: Point-of-care gastric ultrasound (POCUS) immediately pre-op to assess gastric volume The evidence: Silveira et al. (Anesthesiology, 2024) prospectively evaluated gastric volumes by ultrasound in 142 patients on GLP-1 RAs versus 142 matched controls presenting for elective surgery after standard fasting. GLP-1 RA patients had significantly higher residual gastric volumes (1.48 mL/kg vs 0.62 mL/kg, p<0.001), with 23% exceeding the "full stomach" threshold (>1.5 mL/kg) versus 3% of controls. The aspiration risk is real and quantifiable. The wound healing concern is less well-established but should be considered in the overall risk-benefit of perioperative GLP-1 RA management. One practical issue: for patients on semaglutide for T2D, holding the drug for 3 weeks means 3 weeks of uncontrolled glycemia — which ALSO impairs wound healing. There's no good answer here. I've started recommending short-acting insulin coverage during the perioperative hold period.
Last edited: Sep 12, 2024 at 12:03 AM
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quinn_sf
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Jun 2024
San Francisco, CA
Sep 11, 2024 at 10:30 PM#4
Relevant data point from vascular surgery: diabetic foot wounds. We have a cohort of T2D patients on GLP-1 RAs who developed diabetic foot ulcers (DFUs). I've been comparing healing trajectories with our historical DFU database. Preliminary (unpublished) analysis: - GLP-1 RA users (n=34): Median time to 50% wound area reduction: 3.2 weeks - Non-GLP-1 RA diabetics, matched for A1c and wound grade (n=68): 4.8 weeks So in chronic wounds in diabetics, GLP-1 RA users actually healed FASTER. This is counterintuitive given the surgical wound data, but there are explanations: 1. Better glycemic control → less glycation of wound matrix proteins → better healing 2. Reduced systemic inflammation → less pro-inflammatory wound environment 3. Improved peripheral perfusion (GLP-1 RAs have known cardiovascular and possibly microvascular benefits) The difference between acute surgical wounds (where GLP-1 RAs might impair healing via nutritional deficiency) and chronic diabetic wounds (where GLP-1 RAs might improve healing via metabolic optimization) could be key. The pathophysiology is different. Turns et al. (Diabetes Care, 2024) published a small RCT (n=60) showing liraglutide improved DFU healing rates compared to standard care (62% healed at 12 weeks vs 38%, p=0.04). Though this needs replication.
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Dr.EndoIndy
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Oct 2024
Indianapolis, IN
Sep 12, 2024 at 1:13 PM#5
The nutritional angle deserves more attention. I'm a nutrition support physician and I've been doing pre-operative nutritional assessments on GLP-1 RA patients scheduled for elective surgery. Findings in our last 40 consecutive pre-op assessments of semaglutide/tirzepatide users: - 45% had albumin <3.5 g/dL (mild hypoalbuminemia) - 30% had prealbumin <20 mg/dL (suggesting recent protein-calorie malnutrition) - 22% had zinc <60 μg/dL - 18% had vitamin D <20 ng/mL - 12% had iron deficiency (ferritin <30 ng/mL) These are all parameters that affect wound healing. The patients weren't clinically "malnourished" by appearance — many still had BMI >30. But their biochemical nutritional status was compromised. My recommendation for any patient on GLP-1 RAs undergoing elective surgery: 1. Pre-operative nutritional lab panel (albumin, prealbumin, zinc, vitamin C, vitamin D, iron studies, B12) at least 4-6 weeks before surgery 2. Aggressive nutritional optimization: high-protein diet (1.5g/kg/day), zinc 50mg/day, vitamin C 500mg BID, vitamin D repletion if deficient 3. Consider holding GLP-1 RA 4 weeks before surgery (not just for aspiration risk but for nutritional recovery) 4. Post-operative protein supplementation until wound healing is complete
Last edited: Sep 12, 2024 at 4:13 PM
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