GLP-1 Agonist Dosing and Management
Initial Dosing and Titration
For liraglutide (Victoza for diabetes, Saxenda for obesity), start at 0.6 mg subcutaneously daily and increase by 0.6 mg weekly until reaching the target dose. 1, 2 For type 2 diabetes, the maintenance dose is 1.2-1.8 mg daily, while for obesity management, titrate to 3.0 mg daily over 4 weeks 3, 1. The slow weekly escalation minimizes gastrointestinal adverse effects, with nausea occurring in 40% of patients versus 14.8% with placebo 1.
For semaglutide (Ozempic for diabetes, Wegovy for obesity), initiate at 0.25 mg subcutaneously weekly and escalate every 4 weeks through 0.5 mg, 1.0 mg, and 1.7 mg to reach the maintenance dose of 2.4 mg weekly after 16 weeks. 4, 1 This gradual titration over 4-week intervals is critical to minimize gastrointestinal side effects, which occur in 53% of patients but are typically mild-to-moderate and transient 4.
For oral semaglutide (Rybelsus), start at 3 mg daily for 30 days, then increase to 7 mg daily, with optional escalation to 14 mg daily if additional glycemic control is needed 4. However, oral formulations are less potent than injectable formulations for weight management 4, 5.
Renal Function Considerations
No dose adjustment is required for liraglutide, semaglutide, or dulaglutide across all stages of chronic kidney disease, including end-stage renal disease (eGFR <15 mL/min/1.73 m²). 3, 4, 1 This makes these agents preferred for long-term use in patients with renal impairment 4. In contrast, exenatide requires caution when eGFR <45 mL/min/1.73 m², and lixisenatide is not recommended with eGFR <30 mL/min/1.73 m² 3, 4.
Pancreatitis History
Use GLP-1 agonists with caution in patients with a history of pancreatitis, and consider alternative therapies. 3, 1 Current guidelines recommend cautious use rather than absolute contraindication, as pancreatitis has been reported in clinical trials but causality has not been definitively established 3, 4. Monitor patients closely for persistent severe abdominal pain, which warrants immediate discontinuation if pancreatitis is suspected 4.
Critical Contraindications
GLP-1 agonists are absolutely contraindicated in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2). 3, 4, 1 This contraindication is based on animal studies showing thyroid C-cell tumors 4. Monitor for symptoms of thyroid tumors including neck mass, dysphagia, dyspnea, or persistent hoarseness 1.
Drug Interactions and Combination Therapy
Do not combine GLP-1 receptor agonists with other GLP-1 agonists or DPP-4 inhibitors. 4, 1 When using with insulin or sulfonylureas, reduce the dose of insulin by approximately 20% and consider discontinuing or reducing sulfonylurea doses by 50% to prevent hypoglycemia 4, 1. The glucose-dependent mechanism of GLP-1 agonists results in minimal hypoglycemia risk when used as monotherapy 3, 4.
Perioperative Management
For elective surgery requiring anesthesia, discontinue semaglutide at least 3 weeks (three half-lives) before surgery, and liraglutide 3 days before surgery. 4, 1 This is necessary because GLP-1 agonists delay gastric emptying, creating aspiration risk even with extended fasting periods 4, 1. Retained gastric contents are documented in 24.2% of semaglutide users versus 5.1% of controls despite 10-14 day discontinuation and 12-hour fasting 4. For diabetic patients, consult endocrinology to weigh risks and benefits of holding medication 4.
Common Pitfalls to Avoid
- Do not advance doses too rapidly: Gastrointestinal adverse effects are dose-dependent and minimized with slow titration 1, 6, 7
- Do not use cartridge scale to measure dose: Use only the dose selector mechanism 2
- Do not store pen with needle attached: This increases risk of contamination, infection, and inaccurate dosing 2
- Do not skip the flow check for new pens: This ensures proper function before first therapeutic dose 2
- Do not ignore delayed gastric emptying effects: These persist even with long-acting formulations and create perioperative risks 4, 7