Rise of GLP-1 Agonists & Their Side Effects-Slides

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This presentation by Dr. Lily Ackermann reviews the rise of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in managing type 2 diabetes mellitus (T2DM), obesity, and related cardiovascular conditions, highlighting their benefits, mechanisms, side effects, and perioperative considerations.<br /><br />GLP-1 RAs, including long-acting agents like dulaglutide, liraglutide, semaglutide, and the dual GLP-1/GIP agonist tirzepatide, exert their effects by stimulating glucose-dependent insulin release, suppressing glucagon, delaying gastric emptying, promoting satiety, and enabling significant glycemic control (A1C reductions up to 2.5%) and weight loss (up to 50 lbs with tirzepatide). These agents also confer cardiovascular benefits by reducing major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and stroke, by approximately 12-15% in patients with T2DM and obesity, as demonstrated in large randomized controlled trials and meta-analyses.<br /><br />Beyond glycemic and weight control, GLP-1 RAs have benefits in diabetic kidney disease by reducing albuminuria and slowing glomerular filtration rate decline, and show promise in nonalcoholic steatohepatitis (NASH) with improved resolution and fibrosis outcomes. Use in type 1 diabetes has shown some benefits but remains unapproved.<br /><br />Common adverse effects include dose-dependent gastrointestinal symptoms (nausea, vomiting, diarrhea), with warnings about rare risks: pancreatitis, biliary disease (increased cholelithiasis/cholecystitis risk), gastroparesis, and potential retinopathy worsening mostly due to rapid glucose lowering. GLP-1 RAs carry a boxed warning for thyroid C-cell tumors in rodents, contraindicated with medullary thyroid cancer or MEN2.<br /><br />A critical clinical concern is delayed gastric emptying causing retained gastric contents even after fasting, raising aspiration risk under anesthesia. This necessitates holding weekly GLP-1 RAs at least one week prior to elective procedures, with special fasting protocols and consideration of gastric ultrasound to assess residual contents. Current guidelines recommend discontinuing GLP-1 RAs preoperatively to mitigate aspiration risk, although optimal timing remains uncertain.<br /><br />In summary, GLP-1 RAs represent a paradigm shift in T2DM and obesity management with robust cardiovascular and metabolic benefits, but require careful management to balance efficacy with side effects and procedural safety.

Keywords

GLP-1 receptor agonists

type 2 diabetes mellitus

obesity management

cardiovascular benefits

glycemic control

weight loss

diabetic kidney disease

nonalcoholic steatohepatitis (NASH)

perioperative considerations

adverse effects