GLP-1 agonists: Difference between revisions

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==Background==
==Background==
* Synthetic glucagon-like peptide-1 (GLP-1) receptor agonists
*Glucagon-like peptide-1 (GLP-1) receptor agonists are synthetic analogs of the incretin hormone GLP-1
* Released by L-cells of the small intestinge in response to the presence of nutrients
*Endogenous GLP-1 is released by intestinal L-cells in response to nutrient intake
* Stimulate insulin release from pancreatic islet cells. It does this by stimulating glucose-dependent insulin release in the islet cells of the pancreas
*Mechanism of action:
* Slows gastric emptying times
**Stimulates glucose-dependent insulin secretion from pancreatic beta cells (minimal hypoglycemia risk as monotherapy)
* Increases satiety, which decreases drive for food intake
**Suppresses glucagon secretion
**Slows gastric emptying
**Increases central satiety signaling, reducing food intake
*~1 in 8 US adults now use a GLP-1 RA for diabetes, weight loss, or cardiovascular risk reduction<ref name="ASA2024">Multisociety Clinical Practice Guidance for the Safe Use of Glucagon-like Peptide-1 Receptor Agonists in the Perioperative Period. Clin Gastroenterol Hepatol. 2024. doi:10.1016/j.cgh.2024.10.012</ref>
*Two structural categories:
**Exendin-4 based (exenatide, lixisenatide) — derived from Gila monster saliva peptide
**Human GLP-1 based (liraglutide, semaglutide, dulaglutide) — modified human GLP-1 with extended half-life
*Tirzepatide is a dual GLP-1/GIP receptor agonist (not a pure GLP-1 RA)


==Types==
{{GLP-1 Agonist Types}}
{| class="wikitable"
|-
! Short Acting !! Dose
|-
| Exenatide(Byetta) || 5-10 mcg SC bid
|-
| Liraglutide(Victoza) || 0.6-1.8 mg SC daily
|-
! Long Acting !!
|-
| Exenatide(Bydureon) || 2 mg SC qwk
|-
| Albiglutide(Tanzeum) || 30-50 mg SC qwk
|-
| Dulaglutide(Trulicity) || 0.75-1.5 mg qwk
|}


==Indication==
==Indications==
* Diabetes Mellitus, Type 2
*Type 2 [[diabetes mellitus]] — all GLP-1 RAs are approved; recommended as first-line pharmacotherapy (alongside metformin) for patients with established ASCVD or high CV risk per ADA guidelines<ref>American Diabetes Association Professional Practice Committee. Standards of Care in Diabetes—2025. Diabetes Care. 2025;48(Suppl 1).</ref>
*Obesity/overweight — FDA-approved agents:
**Semaglutide 2.4 mg SC weekly (Wegovy) and oral semaglutide 25 mg (Wegovy Pill, approved December 2025)
**Liraglutide 3.0 mg SC daily (Saxenda)
**Tirzepatide (Zepbound) — approved for obesity
*Cardiovascular risk reduction — semaglutide (Wegovy) approved for CV event reduction in patients with CVD and obesity/overweight; liraglutide and dulaglutide have demonstrated CV benefit<ref>Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563</ref>
*Chronic kidney disease — semaglutide (Ozempic) approved January 2025 for CKD risk reduction in T2DM
*Obstructive sleep apnea — tirzepatide (Zepbound) approved 2024 for moderate-to-severe OSA with obesity


==Adverse Reactions==
==Adverse Reactions==
* Nausea, vomiting, diarrhea
===Common===
* Acute pancreatitis
*GI effects (most common, dose-dependent, usually improve with time):
* Exenatide should not be used in patients with creatinine clearance below 30mL/min
**[[Nausea]], [[vomiting]], [[diarrhea]], [[constipation]], abdominal pain
* Should not be used if personal of family history of medullary thyroid cancer or MEN 2A/2B
**Typically worst during dose initiation and up-titration
*Injection site reactions
*Headache
 
===Serious===
*Acute [[pancreatitis]] — rare but potentially fatal (including hemorrhagic and necrotizing); discontinue if suspected and do not restart if confirmed<ref name="StatPearls">Shaefer CF Jr, Engel SS, Engel JR, et al. Glucagon-Like Peptide-1 Receptor Agonists. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024.</ref>
*Cholelithiasis / acute [[cholecystitis]] — increased incidence reported, especially with higher doses and rapid weight loss
*Acute kidney injury — reported in setting of severe GI symptoms (dehydration from nausea/vomiting/diarrhea)
*Medullary thyroid carcinoma risk (observed in rodent studies; clinical significance uncertain)
*Ileus / [[bowel obstruction]] — case reports of GI dysmotility
*Hypoglycemia — low risk as monotherapy; increased risk when combined with [[sulfonylurea]] or [[insulin]]
 
===Contraindications===
*Personal or family history of medullary thyroid carcinoma (MTC)
*MEN type 2
*History of [[pancreatitis]] (relative; use with caution)
*Exenatide (Byetta) specifically: avoid if CrCl <30 mL/min
*''Semaglutide and dulaglutide do not require renal dose adjustment, but monitor renal function with GI side effects''
 
==ED-Relevant Considerations==
===Aspiration Risk During Procedural Sedation and Intubation===
*GLP-1 RAs delay gastric emptying, leading to potential retained gastric contents despite standard fasting<ref name="ASA2024"/>
*For urgent/emergent procedures: treat as full stomach and proceed with rapid sequence intubation<ref name="ASA2023">Joshi GP, Abdelmalak BB, Weigel WA, et al. American Society of Anesthesiologists Consensus-Based Guidance on Preoperative Management of Patients on Glucagon-Like Peptide-1 Receptor Agonists. ASA. June 2023.</ref>
*The 2024 multisociety guidance (ASA, AGA, ASMBS) advises most patients may continue GLP-1 RAs before elective surgery, with individualized risk assessment<ref name="ASA2024"/>
**If GI symptoms suggest delayed emptying: consider liquid diet for 24h prior to procedure, or gastric POCUS to assess stomach contents
**Meta-analyses (>300,000 patients) show retained gastric contents are significantly increased in GLP-1 RA users, but actual aspiration rates remain low (0.1-0.2%)<ref>Perioperative Management of GLP-1 Receptor Agonists: Balancing Aspiration Risk with Therapeutic Benefit. SN Compr Clin Med. 2025. doi:10.1007/s42399-025-02079-9</ref>
*Practical ED approach: Ask about GLP-1 RA use when planning procedural sedation; consider gastric POCUS; have suction ready; use RSI if intubating
 
===Other ED Considerations===
*GLP-1 RA use may cause dehydration and AKI in patients with severe GI side effects — check renal function, resuscitate appropriately
*May present with hypoglycemia if combined with sulfonylureas or insulin — treat per standard protocol
*Severe nausea/vomiting may be the primary complaint — consider GLP-1 RA as contributing cause; may require IV fluids, antiemetics, and medication adjustment by prescriber
*Pancreatitis workup: maintain high index of suspicion for pancreatitis in patients on GLP-1 RAs presenting with severe abdominal pain
*Altered drug absorption: delayed gastric emptying may affect timing and absorption of co-administered oral medications


==See Also==
==See Also==
[[Diabetes medications]]
*[[GLP-1 receptor agonist toxicity]]
*[[Diabetes medications]]
*[[Hypoglycemia]]
*[[Pancreatitis]]
*[[Pneumonia|Aspiration pneumonia]]
*[[Procedural sedation]]
 
==External Links==
*[https://www.asahq.org/about-asa/newsroom/news-releases/2024/10/new-multi-society-glp-1-guidance ASA 2024 Multisociety GLP-1 Perioperative Guidance]
*[https://emcrit.org/ibcc/ EMCrit IBCC]


==References==
==References==
1.Epocrates
<references/>


2.http://www.uptodate.com/contents/glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-type-2-diabetes-mellitus?source=see_link&sectionName=GLUCAGON-LIKE+PEPTIDE-1&anchor=H2#H619400
[[Category:Pharmacology]]
[[Category:Endocrinology]]

Latest revision as of 09:11, 22 March 2026

Background

  • Glucagon-like peptide-1 (GLP-1) receptor agonists are synthetic analogs of the incretin hormone GLP-1
  • Endogenous GLP-1 is released by intestinal L-cells in response to nutrient intake
  • Mechanism of action:
    • Stimulates glucose-dependent insulin secretion from pancreatic beta cells (minimal hypoglycemia risk as monotherapy)
    • Suppresses glucagon secretion
    • Slows gastric emptying
    • Increases central satiety signaling, reducing food intake
  • ~1 in 8 US adults now use a GLP-1 RA for diabetes, weight loss, or cardiovascular risk reduction[1]
  • Two structural categories:
    • Exendin-4 based (exenatide, lixisenatide) — derived from Gila monster saliva peptide
    • Human GLP-1 based (liraglutide, semaglutide, dulaglutide) — modified human GLP-1 with extended half-life
  • Tirzepatide is a dual GLP-1/GIP receptor agonist (not a pure GLP-1 RA)

GLP-1 Agonist Types

Drug (Brand) Class Dose Route Frequency Key Indications
Daily Dosing
Exenatide (Byetta) GLP-1 RA (exendin-4 based) 5-10 mcg SC BID T2DM
Lixisenatide (Adlyxin) GLP-1 RA (exendin-4 based) 10-20 mcg SC Daily T2DM
Liraglutide (Victoza) GLP-1 RA (human GLP-1 based) 0.6-1.8 mg SC Daily T2DM, CV risk reduction
Liraglutide (Saxenda) GLP-1 RA (human GLP-1 based) 3.0 mg SC Daily Obesity/overweight
Weekly Dosing
Semaglutide (Ozempic) GLP-1 RA (human GLP-1 based) 0.25-2 mg SC Weekly T2DM, CV risk reduction, CKD
Semaglutide (Wegovy) GLP-1 RA (human GLP-1 based) 0.25-2.4 mg SC Weekly Obesity/overweight, CV risk reduction
Semaglutide (Rybelsus) GLP-1 RA (human GLP-1 based) 3-14 mg PO Daily T2DM
Semaglutide (Wegovy Pill) GLP-1 RA (human GLP-1 based) 1.5-25 mg PO Daily Obesity/overweight
Dulaglutide (Trulicity) GLP-1 RA (human GLP-1 based) 0.75-4.5 mg SC Weekly T2DM, CV risk reduction
Tirzepatide (Mounjaro) Dual GLP-1/GIP RA 2.5-15 mg SC Weekly T2DM
Tirzepatide (Zepbound) Dual GLP-1/GIP RA 2.5-15 mg SC Weekly Obesity/overweight, OSA
  • Albiglutide (Tanzeum) — discontinued 2017 (commercial reasons, not safety); removed from table
  • Exenatide ER (Bydureon BCise) — discontinued 2023; brand Byetta discontinued 2024 (generic exenatide available)

ED-Relevant Considerations

  • Delayed gastric emptying — all GLP-1 RAs slow gastric motility; important for:
    • Aspiration risk during procedural sedation and intubation (consider NPO status unreliable)
    • Altered absorption of co-administered oral medications
    • 2023 ASA guidance recommends holding GLP-1 RAs prior to elective procedures requiring anesthesia
  • Pancreatitis — rare but serious; discontinue if pancreatitis confirmed
  • Hypoglycemia — low risk as monotherapy; increased risk when combined with sulfonylurea or insulin
  • Nausea/vomiting — most common adverse effect; dose-dependent, typically improves with time
  • Injection site reactions — generally mild
  • Cholelithiasis/cholecystitis — increased incidence reported
  • Contraindicated in personal/family history of medullary thyroid carcinoma or MEN type 2

Indications

  • Type 2 diabetes mellitus — all GLP-1 RAs are approved; recommended as first-line pharmacotherapy (alongside metformin) for patients with established ASCVD or high CV risk per ADA guidelines[2]
  • Obesity/overweight — FDA-approved agents:
    • Semaglutide 2.4 mg SC weekly (Wegovy) and oral semaglutide 25 mg (Wegovy Pill, approved December 2025)
    • Liraglutide 3.0 mg SC daily (Saxenda)
    • Tirzepatide (Zepbound) — approved for obesity
  • Cardiovascular risk reduction — semaglutide (Wegovy) approved for CV event reduction in patients with CVD and obesity/overweight; liraglutide and dulaglutide have demonstrated CV benefit[3]
  • Chronic kidney disease — semaglutide (Ozempic) approved January 2025 for CKD risk reduction in T2DM
  • Obstructive sleep apnea — tirzepatide (Zepbound) approved 2024 for moderate-to-severe OSA with obesity

Adverse Reactions

Common

  • GI effects (most common, dose-dependent, usually improve with time):
  • Injection site reactions
  • Headache

Serious

  • Acute pancreatitis — rare but potentially fatal (including hemorrhagic and necrotizing); discontinue if suspected and do not restart if confirmed[4]
  • Cholelithiasis / acute cholecystitis — increased incidence reported, especially with higher doses and rapid weight loss
  • Acute kidney injury — reported in setting of severe GI symptoms (dehydration from nausea/vomiting/diarrhea)
  • Medullary thyroid carcinoma risk (observed in rodent studies; clinical significance uncertain)
  • Ileus / bowel obstruction — case reports of GI dysmotility
  • Hypoglycemia — low risk as monotherapy; increased risk when combined with sulfonylurea or insulin

Contraindications

  • Personal or family history of medullary thyroid carcinoma (MTC)
  • MEN type 2
  • History of pancreatitis (relative; use with caution)
  • Exenatide (Byetta) specifically: avoid if CrCl <30 mL/min
  • Semaglutide and dulaglutide do not require renal dose adjustment, but monitor renal function with GI side effects

ED-Relevant Considerations

Aspiration Risk During Procedural Sedation and Intubation

  • GLP-1 RAs delay gastric emptying, leading to potential retained gastric contents despite standard fasting[1]
  • For urgent/emergent procedures: treat as full stomach and proceed with rapid sequence intubation[5]
  • The 2024 multisociety guidance (ASA, AGA, ASMBS) advises most patients may continue GLP-1 RAs before elective surgery, with individualized risk assessment[1]
    • If GI symptoms suggest delayed emptying: consider liquid diet for 24h prior to procedure, or gastric POCUS to assess stomach contents
    • Meta-analyses (>300,000 patients) show retained gastric contents are significantly increased in GLP-1 RA users, but actual aspiration rates remain low (0.1-0.2%)[6]
  • Practical ED approach: Ask about GLP-1 RA use when planning procedural sedation; consider gastric POCUS; have suction ready; use RSI if intubating

Other ED Considerations

  • GLP-1 RA use may cause dehydration and AKI in patients with severe GI side effects — check renal function, resuscitate appropriately
  • May present with hypoglycemia if combined with sulfonylureas or insulin — treat per standard protocol
  • Severe nausea/vomiting may be the primary complaint — consider GLP-1 RA as contributing cause; may require IV fluids, antiemetics, and medication adjustment by prescriber
  • Pancreatitis workup: maintain high index of suspicion for pancreatitis in patients on GLP-1 RAs presenting with severe abdominal pain
  • Altered drug absorption: delayed gastric emptying may affect timing and absorption of co-administered oral medications

See Also

External Links

References

  1. ↑ 1.0 1.1 1.2 Multisociety Clinical Practice Guidance for the Safe Use of Glucagon-like Peptide-1 Receptor Agonists in the Perioperative Period. Clin Gastroenterol Hepatol. 2024. doi:10.1016/j.cgh.2024.10.012
  2. ↑ American Diabetes Association Professional Practice Committee. Standards of Care in Diabetes—2025. Diabetes Care. 2025;48(Suppl 1).
  3. ↑ Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563
  4. ↑ Shaefer CF Jr, Engel SS, Engel JR, et al. Glucagon-Like Peptide-1 Receptor Agonists. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024.
  5. ↑ Joshi GP, Abdelmalak BB, Weigel WA, et al. American Society of Anesthesiologists Consensus-Based Guidance on Preoperative Management of Patients on Glucagon-Like Peptide-1 Receptor Agonists. ASA. June 2023.
  6. ↑ Perioperative Management of GLP-1 Receptor Agonists: Balancing Aspiration Risk with Therapeutic Benefit. SN Compr Clin Med. 2025. doi:10.1007/s42399-025-02079-9
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