What is the recommended dosage of semaglutide (glucagon-like peptide-1 receptor agonist) for an adult patient with type 2 diabetes or obesity?

Semaglutide Dosing for Type 2 Diabetes and Obesity

For obesity or overweight with weight-related complications, initiate semaglutide at 0.25 mg subcutaneously once weekly and escalate monthly through 0.5 mg, 1.0 mg, and 1.7 mg to reach the maintenance dose of 2.4 mg weekly over 16 weeks. 1

Standard Dosing Protocol

For Chronic Weight Management (Wegovy)

• Start at 0.25 mg subcutaneously once weekly 1

• Escalate every 4 weeks through the following sequence: 1

  • Week 1-4: 0.25 mg weekly
  • Week 5-8: 0.5 mg weekly
  • Week 9-12: 1.0 mg weekly
  • Week 13-16: 1.7 mg weekly
  • Week 17 onward: 2.4 mg weekly (maintenance dose) 1

• Administer subcutaneously in the abdomen, thigh, or upper arm at any time of day, with or without meals, on the same day each week 1

For Type 2 Diabetes (Ozempic)

• For diabetes management alone, the FDA-approved doses are 0.5 mg or 1.0 mg weekly 2
• Use the same gradual titration schedule starting at 0.25 mg weekly for 4 weeks, then 0.5 mg weekly 2
• May increase to 1.0 mg weekly after at least 4 weeks on 0.5 mg if additional glycemic control is needed 2
• For patients requiring both glycemic control and weight loss, the 2.4 mg dose (Wegovy) is superior and should be prioritized 3

Higher Dose Options for Inadequate Response

Semaglutide 7.2 mg (Investigational)

• A new 7.2 mg maintenance dose is now available for patients with obesity and type 2 diabetes who do not achieve adequate weight loss with 2.4 mg 4
• In the STEP UP T2D trial, semaglutide 7.2 mg achieved -13.2% mean body weight loss versus -3.9% with placebo, with superior HbA1c reduction of -1.5% versus placebo 4
• Safety profile was comparable to 2.4 mg, though dysaesthesia was more common (18.9% vs 4.9%) 4

Semaglutide 2.0 mg for Diabetes

• For patients with type 2 diabetes on 1.0 mg who need additional glycemic control, escalation to 2.0 mg is an option 5
• The SUSTAIN FORTE trial demonstrated superior HbA1c reduction with 2.0 mg versus 1.0 mg (estimated treatment difference -0.23 percentage points, p=0.0003) 5
• Additional weight loss of approximately 0.9 kg was observed with 2.0 mg versus 1.0 mg 5

Mandatory Concomitant Interventions

Semaglutide must be combined with lifestyle modifications—this is not optional: 3

• Implement a minimum 500 kcal/day caloric deficit below total energy requirements 3, 6
• Prescribe at least 150 minutes weekly of structured physical activity 3, 6
• Provide ongoing behavioral counseling for dietary changes 3, 6

Titration Strategy to Minimize Adverse Effects

• Gradual dose escalation over 16 weeks is the most effective strategy to mitigate gastrointestinal side effects 3, 6
• Nausea (44%), diarrhea (32%), vomiting (25%), and constipation (23%) are the most common adverse effects at maximum doses 6
• If gastrointestinal symptoms are severe, maintain the current dose for an additional 4 weeks before continuing escalation 6

Treatment Duration and Discontinuation

• Semaglutide should be considered lifelong therapy to maintain weight loss and cardiometabolic benefits 6
• Discontinuation results in significant weight regain and worsening of cardiometabolic risk factors 6
• The medication provides weight-independent cardiovascular benefits, including reductions in major adverse cardiovascular events in patients with established cardiovascular disease 6

Monitoring Requirements

• Monitor body weight every 4 weeks during dose titration 6
• For patients with type 2 diabetes, monitor glucose levels more frequently during dose escalation 6
• Assess gastrointestinal symptoms at each visit 6
• Once at stable maintenance dose, reevaluate every 3-6 months 6

Critical Safety Considerations and Contraindications

• Absolute contraindication: personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 3, 1
• GLP-1 receptor agonists are associated with increased risk of pancreatitis and gallbladder disease 3, 1
• Monitor for signs of pancreatitis, gallbladder disease, and changes in blood pressure 1
• Semaglutide may delay gastric emptying, potentially affecting absorption of oral medications 2

Special Populations

Renal Impairment

• No dosage adjustments required for any degree of renal impairment, including end-stage renal disease 1, 2
• Renal impairment does not impact semaglutide pharmacokinetics in a clinically relevant manner 2

Hepatic Impairment

• No dosage adjustments required for hepatic impairment 2

Drug Interactions

• Avoid concurrent use with other GLP-1 receptor agonists or DPP-4 inhibitors 1
• Use caution when combining with insulin or insulin secretagogues due to increased hypoglycemia risk 1
• However, hypoglycemia risk remains low overall with semaglutide due to its glucose-dependent mechanism 4

Missed Dose Management

• If one dose is missed, resume at the next scheduled dose 1
• If two consecutive doses are missed, use clinical judgment considering the patient's tolerance to determine whether to resume at the current dose or step back to a lower dose 1

Common Pitfalls to Avoid

• Do not escalate doses too rapidly—this is the primary cause of treatment discontinuation due to gastrointestinal intolerance 3, 6
• Do not prescribe semaglutide without concurrent lifestyle interventions—the medication is approved only as an adjunct to diet and exercise 3
• Do not use oral semaglutide for obesity management—it is FDA-approved only for type 2 diabetes, not obesity 3
• Do not assume 0.5 mg or 1.0 mg doses are adequate for weight management—the 2.4 mg dose provides substantially greater weight loss 7, 8