How do we use GLP-1 (Glucagon-Like Peptide-1) receptor agonists in admitted patients with hyperglycemia?

GLP-1 Receptor Agonists in Hospitalized Patients

GLP-1 receptor agonists can be safely continued or initiated in non-ICU hospitalized patients with type 2 diabetes and mild-to-moderate hyperglycemia (<180 mg/dL), particularly when combined with basal insulin, but should be avoided in critically ill patients, those with severe hyperglycemia (>300 mg/dL), recent heart failure decompensation, or planned surgery requiring general anesthesia. 1

Clinical Decision Algorithm

Appropriate Candidates for GLP-1 Use:

• Non-ICU patients with mild-to-moderate hyperglycemia (<10 mmol/L or <180 mg/dL) can receive GLP-1 receptor agonists, especially when combined with basal insulin for optimal glycemic control 1

• Perioperative cardiac surgery patients may benefit from preoperative liraglutide treatment, which demonstrates insulin-sparing effects (43% requiring intraoperative insulin vs 61% with placebo, p=0.003) and improved postoperative left ventricular function (68% achieving normal function vs 53% placebo, p=0.049) 2, 1

• Patients already on GLP-1 therapy admitted for medical conditions without contraindications can continue their home regimen 1

• Combination therapy with basal insulin achieves superior glycemic control, with exenatide plus basal insulin resulting in 78% of glucose readings within target range (3.9-10.0 mmol/L) compared to 62% with exenatide alone or 63% with basal-bolus insulin 1

Absolute Contraindications:

• Critical illness or ICU patients require continuous insulin infusion as the therapy of choice 1

• Severe hyperglycemia (>16.6 mmol/L or >300 mg/dL) requires basal-bolus insulin regimens instead 1

• Recent heart failure decompensation is a contraindication due to increased HF readmission risk 1

• Type 1 diabetes requires insulin as the agent of choice 1

• Planned surgery with general anesthesia or deep sedation poses increased pulmonary aspiration risk despite prolonged fasting; patients should inform healthcare providers of any planned procedures 2, 1, 3

• Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 3

Practical Implementation Strategy

Dosing and Administration:

• Initiate at low doses and titrate slowly to minimize gastrointestinal side effects 1

• For liraglutide (Victoza): Start at 0.6 mg subcutaneously once daily for one week, then increase to 1.2 mg daily; if additional glycemic control is required, increase to 1.8 mg daily after one week 3

• Inject subcutaneously once daily at any time of day, independently of meals, in the abdomen, thigh, or upper arm 3

• When using with insulin, administer as separate injections; never mix 3

• Add correction doses with rapid-acting insulin before meals or every 6 hours as needed for breakthrough hyperglycemia 1

Monitoring Requirements:

• Monitor glucose levels closely to assess efficacy versus insulin alternatives 1

• Assess bowel movement frequency and consistency at follow-up visits 1

• Watch for signs of bowel obstruction 1

• Monitor for cardiac arrhythmia/tachycardia; consider beta blockers if symptomatic 1

• Reduction in dose of insulin secretagogues or insulin may be necessary to prevent hypoglycemia, particularly in pediatric patients where hypoglycemia risk is higher with GLP-1 agonists regardless of concomitant therapy 3

Critical Safety Concerns

Gastrointestinal Effects:

• Nausea, vomiting, and diarrhea are the most common adverse effects (incidence ≥5%), dose-dependent, and more frequent with short-acting than long-acting formulations 2, 3

• Slow titration increases gastrointestinal tolerability 2

• Increased gastrointestinal side effects may counterbalance glycemic benefits in the hospital setting 1

Pancreatitis:

• Postmarketing reports of fatal and non-fatal hemorrhagic or necrotizing pancreatitis; discontinue promptly if pancreatitis is suspected and do not restart if confirmed 3

• Use with caution in patients with history of pancreatitis 2, 1

Renal Complications:

• Acute kidney injury reported postmarketing, usually associated with nausea, vomiting, diarrhea, or dehydration, sometimes requiring hemodialysis 3

• Use caution when initiating or escalating doses in patients with renal impairment 3

Aspiration Risk:

• Pulmonary aspiration during general anesthesia or deep sedation has been reported in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures despite prolonged fasting 2, 1, 3

Other Serious Adverse Events:

• Hypersensitivity reactions including anaphylaxis and angioedema reported postmarketing; discontinue and seek medical advice promptly 3

• Acute gallbladder disease; if cholelithiasis or cholecystitis suspected, gallbladder studies are indicated 3

• Never share a GLP-1 pen between patients, even if the needle is changed 3

Cardiovascular Considerations

GLP-1 receptor agonists provide cardiovascular benefits in appropriate outpatient populations with established atherosclerotic cardiovascular disease, reducing major adverse cardiovascular events (MACE) by 13-26% 2. However, these cardiovascular outcome trial data should not drive inpatient decision-making, as hospitalized patients represent a different risk-benefit profile where acute safety concerns (aspiration, gastrointestinal complications, hemodynamic instability) take precedence over long-term cardiovascular benefits 1.