What is the recommended usage and dosage of Liraglutide (glucagon-like peptide-1 receptor agonist) for a patient with type 2 diabetes?

Liraglutide for Type 2 Diabetes: Dosing and Usage

For adults with type 2 diabetes, start liraglutide at 0.6 mg subcutaneously once daily for one week, then increase to 1.2 mg daily, with further escalation to 1.8 mg daily if additional glycemic control is needed. 1

Adult Dosing Protocol

Initial Titration:

• Start at 0.6 mg subcutaneously once daily for 1 week - this dose is specifically intended to reduce gastrointestinal symptoms and is not effective for glycemic control 1
• After 1 week, increase to 1.2 mg once daily 1
• If additional glycemic control is required after at least 1 week at 1.2 mg, escalate to the maximum dose of 1.8 mg once daily 1

Administration Details:

• Inject subcutaneously in the abdomen, thigh, or upper arm at any time of day, independent of meals 1
• Rotate injection sites within the same region to reduce risk of cutaneous amyloidosis 1
• When using with insulin, administer as separate injections in the same body region but not adjacent to each other 1

Pediatric Dosing (Ages 10 Years and Older)

For pediatric patients aged 10 years and older with type 2 diabetes:

• Start at 0.6 mg subcutaneously once daily 1
• Increase in 0.6 mg increments after at least 1 week on current dose if additional glycemic control is needed 1
• Maximum dose is 1.8 mg once daily 1

This pediatric indication is supported by a 2019 randomized trial showing liraglutide (up to 1.8 mg daily) added to metformin (with or without basal insulin) decreased A1C by an estimated 1.06 percentage points at 26 weeks and 1.30 at 52 weeks, though it increased gastrointestinal side effects 2

Missed Dose Management

• Resume once-daily dosing with the next scheduled dose - do not double up 1
• If more than 3 days have elapsed since the last dose, reinitiate at 0.6 mg once daily to mitigate gastrointestinal symptoms, then retitrate at the healthcare provider's discretion 1

Clinical Context and Evidence

Cardiovascular Benefits: Liraglutide is indicated to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes and established cardiovascular disease 1. The FDA-approved indication specifies initiating at 0.6 mg subcutaneously daily and titrating slowly to 1.8 mg or maximally tolerated dose 2

Perioperative Use: In the perioperative setting, 0.6 mg subcutaneous liraglutide given the evening before surgery has demonstrated superior glycemic control compared to insulin, with median blood glucose 1 hour after surgery of 6.6 mmol/L versus 7.5 mmol/L with insulin infusion (p=0.006) 2. This single preoperative dose resulted in an 18% absolute reduction in patients requiring insulin postoperatively 2

Hospital Use: For hospitalized patients with type 2 diabetes undergoing elective surgery, perioperative liraglutide demonstrated better glycemic control with lower insulin requirements compared to standard insulin therapy 2

Contraindications and Critical Warnings

Absolute Contraindications:

• Personal or family history of medullary thyroid carcinoma (MTC) 1
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1
• Serious hypersensitivity reaction to liraglutide or excipients 1

Black Box Warning: Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors in rodents at clinically relevant exposures. While human relevance is uncertain, counsel patients about potential MTC risk and symptoms (neck mass, dysphagia, dyspnea, persistent hoarseness) 1

Renal and Hepatic Considerations

No dose adjustment is required for renal or hepatic impairment 2, though data in end-stage renal disease are limited 2. Drug exposure is reduced with mild, moderate, or severe renal or hepatic impairment, but this does not necessitate dose changes 3

Common Pitfalls to Avoid

• Do not skip the initial 0.6 mg week - this titration period is essential to minimize gastrointestinal side effects (nausea, vomiting, diarrhea), which are the most common adverse events 1, 4, 5
• Do not use in type 1 diabetes - liraglutide is contraindicated in this population 1. Limited data in type 1 diabetes show modest A1C reductions (0.4%) but this is not an approved indication 2
• Do not coadminister with other liraglutide-containing products (such as Saxenda for weight management at 3.0 mg dose) 1
• Slower dose titration is effective in managing gastrointestinal side effects - consider extending the time at each dose level if patients experience significant nausea 2

Expected Outcomes

Glycemic Control: Liraglutide at 1.2 or 1.8 mg once daily produces A1C reductions of approximately 1.0-1.5% from baseline values of 8.2-8.4% 4, 5, 6

Weight Effects: Liraglutide generally leads to body weight loss through reduced appetite, increased satiety, and delayed gastric emptying 3, 4, 5

Hypoglycemia Risk: The glucose-dependent mechanism of insulin release results in a low risk of hypoglycemia when used as monotherapy or with non-secretagogue medications 3, 7. When combined with insulin or sulfonylureas, a lower dose of the insulin secretagogue may be required 2