GLP-1 RA Adjustment During Fasting Periods
Primary Recommendation for SGLT2 Inhibitors (Not GLP-1 RAs)
It is reasonable to withhold SGLT2 inhibitors during times of prolonged fasting, surgery, or critical medical illness when patients may be at greater risk for ketosis, but this specific guidance does not apply to GLP-1 receptor agonists. 1
GLP-1 RA Management During Fasting: Evidence-Based Approach
For Patients with Type 2 Diabetes on GLP-1 RAs
Continue GLP-1 receptor agonists during short-term fasting periods (up to 32 hours) without dose adjustment, as hypoglycemia risk remains minimal due to the glucose-dependent mechanism of action. 2
A prospective study of 12 severely obese patients with type 2 diabetes on liraglutide up to 3.0 mg daily demonstrated no hypoglycemia during a 32-hour preoperative fast, suggesting safe continuation during perioperative fasting 2
GLP-1 receptor agonists augment insulin secretion and suppress glucagon only during hyperglycemia or euglycemia, making hypoglycemia unlikely during fasting when used as monotherapy 3
The glucose-dependent nature of insulin stimulation and glucagon suppression explains the low likelihood of hypoglycemia with GLP-1 receptor agonists 4
Critical Distinction: Peri-Operative vs. Religious/Intermittent Fasting
For elective surgery requiring anesthesia, discontinue GLP-1 RAs well in advance (3 weeks for semaglutide/tirzepatide, 3 days for liraglutide) due to delayed gastric emptying and aspiration risk, not hypoglycemia concerns. 1, 4
Retained gastric contents are documented even after extended fasting periods in patients on GLP-1 RAs, with 24.2% of semaglutide users showing increased residual gastric content versus 5.1% of controls despite 10-14 day discontinuation and 12-hour fasting 1
This aspiration risk applies to both oral and injectable formulations and persists despite prolonged fasting 1, 4
Concomitant Medication Adjustments
Reduce basal insulin by 20% when continuing GLP-1 RAs during fasting periods in patients with HbA1c ≤8%, and strongly consider discontinuing or reducing prandial insulin by 50%. 5, 4
When GLP-1 RAs are combined with insulin or insulin secretagogues, hypoglycemia risk increases and requires dose reduction of these agents 1, 6
Sulfonylurea doses may need reduction when used concomitantly with GLP-1 RAs during fasting 1
Monitoring Requirements During Fasting
Check fasting glucose daily and monitor for signs of dehydration, as GLP-1 RAs can cause gastrointestinal fluid losses that may be exacerbated during fasting. 4
Monitor blood pressure as volume depletion may occur, particularly in elderly patients 4
Be vigilant for gastrointestinal symptoms (nausea, vomiting, diarrhea) which are common with GLP-1 RAs and may worsen during fasting 3, 6
Specific Agent Considerations
No dose adjustment is required for dulaglutide, liraglutide, or semaglutide across all stages of CKD during fasting periods. 1
Long-acting GLP-1 RAs (liraglutide, once-weekly exenatide, dulaglutide, semaglutide) have more profound effects on overnight and fasting plasma glucose 3
Short-acting agents (exenatide twice daily, lixisenatide) have reduced effectiveness on overnight and fasting plasma glucose but maintain their effect on gastric emptying 3
Common Pitfalls to Avoid
Do not automatically discontinue GLP-1 RAs for religious fasting (Ramadan) or intermittent fasting protocols, as the hypoglycemia risk is minimal when used without insulin secretagogues 2
Do not confuse peri-operative fasting guidelines (which require discontinuation due to aspiration risk) with general fasting guidance (where continuation is safe) 1, 2
Do not fail to reduce insulin doses when continuing GLP-1 RAs during fasting, as this combination significantly increases hypoglycemia risk 5, 4
Duration Limitations
For fasting periods exceeding 32 hours, evidence for safe continuation of GLP-1 RAs is limited and requires clinical judgment with intensive glucose monitoring. 2