Wegovy (Semaglutide) Injection: Comprehensive Overview
What is Wegovy?
Wegovy is a once-weekly subcutaneous injection containing semaglutide 2.4 mg, FDA-approved for chronic weight management in adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity, and must be used alongside reduced-calorie diet and increased physical activity. 1, 2
Mechanism of Action
Wegovy works through multiple pathways to produce weight loss 1, 3:
- Appetite suppression via hypothalamic GLP-1 receptors that regulate satiety 1, 2
- Delayed gastric emptying by inhibiting gastric peristalsis and increasing pyloric tone 1
- Glucose-dependent insulin secretion from pancreatic β-cells 1, 2
- Decreased glucagon secretion to reduce hepatic glucose production 1
- Enhanced pancreatic β-cell growth and protection against apoptosis 2
The absolute bioavailability is 89%, with maximum concentration reached 1-3 days post-dose and steady-state achieved after 4-5 weeks of weekly administration 4
Dosing and Administration
The critical dosing protocol requires slow titration to minimize gastrointestinal side effects 1, 2:
- Weeks 1-4: 0.25 mg weekly 1, 2
- Weeks 5-8: 0.5 mg weekly 1, 2
- Weeks 9-12: 1.0 mg weekly 1, 2
- Weeks 13-16: 1.7 mg weekly 1, 2
- Week 17+: 2.4 mg weekly (maintenance dose) 1, 2
Starting at high doses bypasses the body's adaptation period and dramatically increases gastrointestinal side effects 1. Injections can be administered in the abdomen, thigh, or upper arm with similar exposure 4.
Missed Dose Protocol
- If 2 consecutive doses missed and previously tolerated well: Resume at same dose 1
- If 3+ consecutive doses missed: Restart the titration schedule 1, 2
Weight Loss Efficacy
Wegovy demonstrates the largest weight loss of any obesity medication to date 2, 3:
- Mean weight loss of 14.9-17.4% at 68 weeks in non-diabetic patients with obesity 1, 2, 3
- 64.9% of patients achieve ≥10% total body weight loss 2
- Real-world data shows mean weight loss of 13.4% at 6 months, 17.6% at 12 months, 20.3% at 18 months, and 20.4% at 24 months 5
- Weight loss is consistently greater in non-diabetic patients (6.1-17.4%) compared to those with diabetes (4-6.2%) 2
Cardiovascular Benefits
Wegovy provides significant cardiovascular risk reduction beyond weight loss 1, 2:
- 20% reduction in composite cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.80) in patients with obesity and established cardiovascular disease 1, 2
- Major cardiovascular events occurred in 6.5% of Wegovy-treated patients versus 8% in placebo in the SELECT trial 1
- Improvements in cholesterol profiles, blood pressure, and inflammatory markers 1
Common Side Effects
Gastrointestinal symptoms are the predominant side effects, occurring in the majority of patients but typically being transient and dose-dependent 1, 2:
- Nausea: 17-44% of patients 1, 2
- Diarrhea: 12-32% 1, 2
- Vomiting: 7-25% 1, 2
- Constipation: 10-23% 1, 2
- Abdominal pain 1
- Esophageal reflux due to delayed gastric emptying 1
Management Strategies for GI Side Effects
- Reduce meal size to manage nausea and vomiting 1
- Limit alcohol and carbonated drinks to reduce reflux symptoms 1
- Avoid high-fat diets to help with constipation 1
- Slow dose titration minimizes these effects 1, 2
Serious Adverse Events
Wegovy carries a 38% higher risk of serious adverse events compared to placebo 1:
- Pancreatitis: Reported in clinical trials, though causality not definitively established 1, 2
- Gallbladder disease: Increased risk of cholelithiasis (gallstones) and cholecystitis requiring monitoring 1, 2
- Acute kidney injury: Risk from dehydration secondary to severe GI effects, particularly in patients with pre-existing kidney disease 1, 2
- Elevated heart rate: Mean increase of 2-3 beats per minute 1
- Injection site reactions: Reported in 0.2% of patients 4
- Suicidal ideation: Reported in clinical trials 1
Absolute Contraindications
Wegovy is absolutely contraindicated in the following situations 1, 2:
- Personal or family history of medullary thyroid carcinoma (MTC) 1, 2, 4
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1, 2, 4
- Pregnancy or breastfeeding 1, 2
Wegovy carries an FDA Black Box Warning regarding the risk of thyroid C-cell tumors based on rodent studies 1.
Relative Contraindications and Cautions
- History of pancreatitis: Use with caution 1, 2
- Clinically meaningful gastroparesis: Not recommended 1, 2
- Severe renal impairment or ESRD: Can be used with caution, but requires careful monitoring for dehydration 1, 2
- History of diabetic retinopathy: Monitor closely for progression 1
- Prior gastric surgery (including bariatric surgery): Use with extreme caution 1
Drug Interactions
The risk of hypoglycemia increases when Wegovy is used with insulin or insulin secretagogues 1, 4:
- Reduce insulin dose by 20% when initiating Wegovy 1, 2
- Discontinue or reduce sulfonylurea doses by 50% to prevent hypoglycemia 1, 2
- Do not combine with other GLP-1 receptor agonists or DPP-4 inhibitors 2
Delayed gastric emptying may affect absorption of oral medications 1, 4:
- For oral hormonal contraceptive users: Switch to non-oral contraception or add barrier method for 4 weeks after initiation and each dose escalation 1
- Medications with narrow therapeutic index (e.g., warfarin, digoxin): Monitor closely, though clinical pharmacology trials showed no clinically relevant interactions 1, 4
Monitoring Requirements
Regular monitoring is essential during Wegovy treatment 1, 2:
- Every 4 weeks during titration: Assess gastrointestinal tolerance, weight loss progress, blood pressure 2
- Every 3 months minimum after reaching maintenance dose: Monitor weight, blood pressure, cardiovascular risk factors, medication adherence 1, 2
- Renal function: Especially with severe GI symptoms that could lead to dehydration 1, 2
- Signs of pancreatitis: Persistent severe abdominal pain 1, 2
- Gallbladder disease symptoms: Periodic monitoring 1, 2
Treatment Response and Duration
Early responders (≥5% weight loss after 3 months) should continue medication long-term 1, 2:
- If weight loss <5% after 3 months at therapeutic dose: Consider discontinuation and alternative approaches 1, 2
- Lifelong treatment is typically necessary to maintain weight loss 1, 2
- Sudden discontinuation results in regain of one-half to two-thirds of lost weight within 1 year 2
Special Populations
Renal Impairment
No dose adjustment required for any degree of renal impairment, including ESRD 1, 2, 4. However, careful monitoring for gastrointestinal side effects and dehydration is essential 1.
Hepatic Impairment
No dose adjustment required 4.
Pregnancy
Limited data exists on semaglutide use in pregnancy 4. Based on animal studies showing embryofetal mortality and structural abnormalities, Wegovy should only be used during pregnancy if potential benefit justifies potential risk to the fetus 4.
Diabetes
Weight loss appears lower in individuals with type 2 diabetes (4-6.2%) compared to those without diabetes (6.1-17.4%) 2, 6.
Perioperative Considerations
For elective surgery requiring anesthesia, discontinue Wegovy for at least 3 weeks (three half-lives) before surgery 2:
- Retained gastric contents documented even after extended fasting periods (24.2% of semaglutide users vs. 5.1% of controls) 2
- Creates aspiration risk during anesthesia 2
- Consider gastric ultrasound pre-operatively to assess residual gastric contents 2
Cost Considerations
Average wholesale price is approximately $1,557-$1,600 per 30-day supply 2, requiring long-term financial planning as lifelong treatment is typically necessary 2.
Practical Prescribing Pearls
- Combine with lifestyle modifications: 500-kcal reduction below daily requirements, minimum 150 minutes/week physical activity, resistance training to preserve lean body mass 2
- Ensure adequate fluid intake to prevent dehydration-related kidney injury 1
- If patient tolerates submaximal dose well and achieves adequate response: Continuing that dose long-term is acceptable rather than escalating 1
- Payors should cover evidence-based obesity treatments to reduce barriers to treatment access 2