What is the appropriate approach to initiating and managing treatment with Wegovy (semaglutide) for a patient?

Wegovy (Semaglutide 2.4 mg): Initiation and Management Protocol

Patient Eligibility and Selection

Wegovy is indicated for chronic weight management in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease), and must be used as an adjunct to a reduced-calorie diet and increased physical activity. 1

Absolute Contraindications

• Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2) 1, 2
• Pregnancy or breastfeeding 2
• History of severe hypersensitivity reaction to semaglutide 2

Relative Cautions

• History of pancreatitis (use with caution, though causality not definitively established) 1, 2
• Severe gastroparesis or clinically meaningful GI motility disorders 1, 2
• Severe renal impairment (requires careful monitoring but no dose adjustment needed) 3
• History of diabetic retinopathy (monitor closely for progression) 2

Pre-Treatment Evaluation

Required Baseline Assessment

• Document BMI and weight-related comorbidities 1
• Screen for absolute contraindications (personal/family history of MTC or MEN2) 1
• Obtain baseline metabolic parameters: lipid panel (total cholesterol, LDL, HDL, triglycerides), blood pressure, fasting glucose 1
• Assess renal function (eGFR) and liver enzymes 1
• Review all current medications to identify weight-promoting medications and consider alternatives 1
• Document failed lifestyle modifications (diet and exercise) for insurance authorization 1

Concomitant Medication Review

• If patient is on sulfonylureas or insulin, plan for dose reduction to prevent hypoglycemia 1
• Review oral contraceptives: advise switching to non-oral method or adding barrier contraception for 4 weeks after initiation and each dose escalation due to delayed gastric emptying 2
• Assess medications with narrow therapeutic index (warfarin) that may be affected by delayed gastric emptying 2

Dosing and Titration Protocol

The standard titration schedule must be followed to minimize gastrointestinal adverse effects, regardless of patient tolerance claims. 1

Mandatory Titration Schedule

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

Administration Details

• Administer as once-weekly subcutaneous injection 1
• Can be injected in abdomen, thigh, or upper arm with similar exposure 3
• Steady-state exposure achieved after 4-5 weeks of once-weekly administration 3
• Maximum concentration reached 1-3 days post-dose 3

Missed Dose Management

• If ≤4 days since missed dose: administer as soon as possible 1
• If >4 days since missed dose: skip and resume at next scheduled dose 1
• If 2 consecutive doses missed: resume at same dose if previously tolerated 1
• If ≥3 consecutive doses missed: consider restarting titration schedule 1

Monitoring Schedule

During Titration Phase (First 16 Weeks)

• Assess every 4 weeks during dose escalation 1
• Monitor: weight, blood pressure, gastrointestinal tolerance, signs of pancreatitis, signs of gallbladder disease 1
• Check fasting glucose if patient has prediabetes or metabolic syndrome 1

Maintenance Phase (After Week 16)

• Assess at least every 3 months 1
• Monitor: weight stability, blood pressure, cardiovascular risk factors, medication adherence 1
• Evaluate treatment efficacy at 12-16 weeks on maximum tolerated therapeutic dose 1

Critical Decision Point at 3 Months

If weight loss is <5% after 3 months at therapeutic dose, discontinue medication and consider alternative approaches. 1 Early responders (≥5% weight loss after 3 months) should continue long-term unless clinical circumstances suggest otherwise 1.

Expected Outcomes

Weight Loss Efficacy

• Mean weight loss of 14.9% at 68 weeks compared to 2.4% with placebo 4
• 86.4% of patients achieve ≥5% weight loss 4
• 69.1% achieve ≥10% weight loss 4
• 50.5% achieve ≥15% weight loss 4
• Weight loss continues over 65 weeks and can be sustained for up to 4 years 5

Cardiovascular Benefits

• 20% reduction in composite cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.80) in patients with established cardiovascular disease 1
• Improvements in blood pressure, lipid profiles, and inflammatory markers 1

Managing Adverse Effects

Gastrointestinal Side Effects (Most Common)

Nausea, vomiting, diarrhea, constipation, and abdominal pain occur in the majority of patients but are typically dose-dependent, transient, and mild-to-moderate in severity. 2

Mitigation Strategies

• Slow titration minimizes GI side effects 2
• Reduce meal size 1
• Limit alcohol and carbonated beverages 1
• Avoid high-fat diets 2
• Reassure patients that symptoms typically decrease over time 1

Serious Adverse Events Requiring Monitoring

Pancreatitis

• Monitor for persistent severe abdominal pain 1
• Discontinue if pancreatitis suspected 1
• Incidence increased but causality not definitively established 2

Gallbladder Disease

• Increased risk of cholelithiasis and cholecystitis 2
• Monitor for right upper quadrant pain, nausea, vomiting 2
• Risk related to rapid weight loss and altered bile composition 2

Acute Kidney Injury

• Risk particularly high from dehydration secondary to severe GI effects 2
• Monitor renal function closely when initiating or escalating doses, especially in patients with pre-existing kidney disease 2
• Ensure adequate fluid intake 2

Hypoglycemia (When Combined with Other Agents)

• Minimal intrinsic hypoglycemia risk as monotherapy due to glucose-dependent mechanism 1
• Risk increases when combined with insulin or sulfonylureas 2
• Reduce insulin by 20% when initiating Wegovy 1
• Reduce sulfonylurea dose by 50% or discontinue 1

Lifestyle Intervention Requirements

Pharmacotherapy must be combined with lifestyle modifications for optimal results. 1

Mandatory Components

• Reduced-calorie diet: 500-kcal reduction below daily requirements 1
• Physical activity: minimum 150 minutes/week 1
• Resistance training to preserve lean body mass 1
• Behavioral counseling and lifestyle modification support 1

Long-Term Management

Duration of Treatment

Lifelong treatment is typically necessary to maintain weight loss and prevent weight regain. 6, 1 Sudden discontinuation results in regain of one-half to two-thirds of lost weight within 1 year 1.

Weight Regain After Discontinuation

• Weight regain of approximately 11.6% of lost weight occurs after discontinuation 6
• Most patients regain weight without ongoing intervention 6
• If discontinuation necessary, intensify lifestyle interventions immediately and establish monthly weight monitoring for first 6 months 1

Treatment Intensification

If patients fail to achieve weight loss goals at maximum dose:

• Consider adding structured lifestyle management programs 1
• Evaluate for metabolic surgery if BMI criteria met 1
• Consider switching to tirzepatide for superior weight loss (20.9% vs 14.9%) 1

Peri-Operative Considerations

For elective surgery requiring anesthesia, discontinue Wegovy at least 3 weeks (three half-lives) before surgery due to delayed gastric emptying and aspiration risk. 1 Retained gastric contents documented even after extended fasting periods, with 24.2% of semaglutide users showing increased residual gastric content versus 5.1% of controls 1.

Special Populations

Renal Impairment

• No dose adjustment required for any degree of renal impairment, including end-stage renal disease 3
• Careful monitoring required for GI side effects that could lead to dehydration 2

Hepatic Impairment

• No dose adjustment required 3

Cardiovascular Disease

• Prioritize Wegovy for patients with established cardiovascular disease due to proven cardiovascular benefit 1
• Monitor blood pressure as weight loss may necessitate antihypertensive medication adjustment 1

Cost Considerations

• Average wholesale price approximately $1,557-$1,619 per 30-day supply 1
• Insurance authorization may be challenging, particularly for obesity management without diabetes 1
• Document failed lifestyle modifications for insurance approval 1

Critical Pitfalls to Avoid

• Do not start at high doses: Starting at 2.4 mg bypasses the body's adaptation period and dramatically increases risk of severe GI side effects 2
• Do not assume weight loss will be maintained without ongoing intervention: Counsel patients about expected weight regain if medication discontinued 6
• Do not delay follow-up beyond 3 months: Early non-responders unlikely to benefit from continued therapy 1
• Do not ignore peri-operative aspiration risk: Delayed gastric emptying persists independently of appetite suppression 1
• Do not combine with other GLP-1 receptor agonists: Pharmacologically redundant and potentially harmful 1