What is the proper dosing and administration of Ozempic (semaglutide) for an adult patient with type 2 diabetes or obesity?

How to Use Ozempic (Semaglutide)

Start Ozempic 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, combined with a 500 kcal/day caloric deficit and at least 150 minutes of weekly physical activity. 1

Standard Dosing Protocol

The dosing escalation follows a mandatory 5-step protocol over 16 weeks:

• Weeks 1-4: 0.25 mg once weekly 1, 2
• Weeks 5-8: 0.5 mg once weekly 1, 2
• Weeks 9-12: 1.0 mg once weekly 1, 2
• Weeks 13-16: 1.7 mg once weekly 1, 2
• Week 17 onward: 2.4 mg once weekly (maintenance dose) 1, 2

This gradual escalation is the most effective strategy to minimize gastrointestinal side effects, which are the most common adverse events. 3, 1

Administration Technique

• Inject subcutaneously in the abdomen, thigh, or upper arm 1
• Administer at any time of day, with or without meals 1, 2
• Must be given on the same day each week for optimal adherence 1, 2
• The injection site can be rotated with each dose 1

Mandatory Lifestyle Interventions (Not Optional)

Semaglutide must be combined with lifestyle modifications—this is a requirement, not a suggestion:

• Implement a minimum 500 kcal/day caloric deficit below total energy requirements 1
• Prescribe at least 150 minutes weekly of structured physical activity 1
• Provide ongoing behavioral counseling for dietary changes 1

The clinical trials demonstrating semaglutide's efficacy all incorporated these lifestyle interventions, and the medication's effectiveness depends on this combination approach. 3

Managing Gastrointestinal Side Effects

If nausea, vomiting, or other GI symptoms are severe during dose escalation:

• Maintain the current dose for an additional 4 weeks before continuing escalation 1
• Do not skip the gradual titration—jumping doses increases adverse events 3, 1
• Gastrointestinal adverse events (nausea, vomiting, diarrhea, constipation, abdominal pain) occur in approximately 60% of patients but are mostly mild to moderate 3, 4

Missed Dose Management

If one dose is missed:

• Resume at the next scheduled dose 2

If two consecutive doses are missed:

• Use clinical judgment to determine whether to resume at the current dose or step back to a lower dose 1
• Consider the patient's tolerance to the medication when making this decision 2

Absolute Contraindications (Do Not Prescribe)

Semaglutide has an absolute contraindication in patients with:

• Personal history of medullary thyroid cancer 3, 1
• Family history of medullary thyroid cancer 3, 1
• Multiple endocrine neoplasia syndrome type 2 3, 1

This contraindication is based on animal studies showing thyroid C-cell tumors, though human relevance remains unknown. 5

Critical Safety Monitoring

Monitor for these serious adverse events:

• Pancreatitis (increased risk with all GLP-1 receptor agonists) 3, 1, 2
• Gallbladder disease (cholelithiasis, cholecystitis) 3, 1
• Suicidal ideation (reported in clinical trials) 3
• Acute myocardial infarction 3

The pooled estimate from 8 RCTs showed a 38% higher risk of serious adverse events with semaglutide versus placebo (95% CI, 1.10–1.73). 3

Special Populations

Renal impairment:

• No dosage adjustments required for any degree of renal impairment, including end-stage renal disease 1, 2

Hepatic impairment:

• No dosage adjustments required 1

Type 2 diabetes with obesity:

• The 2.4 mg dose is superior for both glycemic control and weight loss and should be prioritized over the 1.0 mg diabetes-only dose 1
• Weight loss appears to be lower in individuals with type 2 diabetes compared to those without diabetes 3

Drug Interactions to Avoid

• Do not use concurrently with other GLP-1 receptor agonists 1, 2
• Do not use concurrently with DPP-4 inhibitors 1, 2
• Use caution when combining with insulin or insulin secretagogues due to increased hypoglycemia risk 1, 2

Treatment Duration

Semaglutide is considered lifelong therapy:

• Discontinuation results in significant weight regain and worsening of cardiometabolic risk factors 1
• This is a chronic disease management medication, not a short-term intervention 1

Expected Outcomes

Weight loss:

• Mean total body weight loss of 10.76% (95% CI, 8.73%–12.80%) at 52-72 weeks 3
• Absolute weight loss ranging from 9.7 to 16.8 kg in clinical trials 3

Glycemic control (in patients with type 2 diabetes):

• HbA1c reduction of 1.3-1.6% compared to baseline 5, 6
• 66-73% of patients achieve HbA1c <7% 5

Common Pitfalls to Avoid

• Do not skip the gradual dose escalation—this dramatically increases GI side effects and treatment discontinuation 3, 1
• Do not prescribe semaglutide without implementing lifestyle interventions—the clinical trial data supporting its use all included dietary and exercise modifications 3, 1
• Do not use the 1.0 mg dose for obesity management—the 2.4 mg dose is FDA-approved for obesity and provides superior weight loss 3, 1
• Do not forget to screen for contraindications—specifically ask about personal and family history of medullary thyroid cancer 3, 1