Wegovy

Wegovy is a brand-name injectable prescription medication containing semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist. It is FDA-approved for chronic weight management in adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related condition, and to reduce cardiovascular risk in adults with established cardiovascular disease and obesity or overweight. It is also approved for weight management in adolescents aged 12 and older with obesity.

How It Works

Wegovy contains semaglutide, a molecule that closely mimics GLP-1, a hormone your body naturally releases after eating. According to the FDA-approved prescribing information (NDA 215256), semaglutide works through three primary pathways:

Wegovy is administered once weekly by subcutaneous injection. Its half-life of approximately one week, as stated in the FDA label, allows for this convenient dosing schedule. The dose is escalated gradually over 16–20 weeks to reach the maintenance dose of 2.4 mg weekly, a schedule designed to minimize gastrointestinal side effects.

Side Effects by Week

Most Common Side Effects

The following side effects were reported in ≥5% of Wegovy-treated patients in STEP clinical trials and are listed in the FDA-approved prescribing information (NDA 215256):

• Nausea: The most frequently reported side effect, occurring in up to 44% of patients in STEP 1 (Wilding et al., NEJM 2021), typically most intense during dose escalation and decreasing over time.
• Diarrhea: Reported in approximately 30% of participants in STEP 1, generally mild to moderate in severity and transient in nature.
• Vomiting: Occurred in up to 24% of Wegovy-treated patients in STEP 1, most common during the early dose escalation phase.
• Constipation: Reported in approximately 24% of patients per FDA labeling, and can persist longer than other gastrointestinal side effects throughout treatment.
• Abdominal pain: Reported in approximately 20% of patients in STEP trials; can range from mild cramping to more significant discomfort requiring evaluation.
• Headache: Reported in approximately 14% of Wegovy-treated patients in STEP 1, typically mild and not requiring discontinuation.
• Fatigue: Reported in approximately 11% of patients in STEP clinical trials, particularly during the initial weeks of treatment.
• Dyspepsia (indigestion): Reported in approximately 9% of patients per FDA prescribing information; includes bloating, burping, and upper abdominal discomfort.
• Dizziness: Reported in approximately 8% of patients across STEP trials, sometimes associated with reduced caloric intake or postural changes.
• Injection site reactions: Redness, bruising, or discomfort at injection site reported in approximately 6–7% of patients per FDA label.
• Hair loss (alopecia): Reported in approximately 3% of patients in STEP trials; generally attributed to rapid weight loss (telogen effluvium) rather than direct drug effect per FDA label discussion.
• Hypoglycemia in patients without diabetes: Not commonly reported in non-diabetic patients, but blood sugar fluctuations can occur, particularly if eating is significantly reduced.

Serious Side Effects

The following serious side effects carry FDA Black Box Warning status or are designated as serious adverse events in the Wegovy prescribing information (NDA 215256). Seek immediate medical attention if any occur:

• 🔴 [BLACK BOX WARNING] Thyroid C-Cell Tumors: Semaglutide caused thyroid C-cell tumors in rodent studies at clinically relevant exposures per FDA label. It is unknown whether Wegovy causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans. Wegovy is contraindicated in patients with a personal or family history of MTC or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Patients should report neck lumps, hoarseness, difficulty swallowing, or shortness of breath immediately.
• 🔴 Acute Pancreatitis: Serious cases of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, have been reported with GLP-1 receptor agonists per FDA label. Wegovy should be discontinued if pancreatitis is suspected. Symptoms include severe and persistent abdominal pain radiating to the back, with or without vomiting.
• 🔴 Acute Gallbladder Disease: In STEP 1, cholelithiasis (gallstones) was reported in 1.6% of Wegovy patients versus 0.7% of placebo patients (Wilding et al., NEJM 2021). Cholecystitis was also reported. Rapid weight loss increases gallstone risk. Severe abdominal pain, especially upper right quadrant, requires prompt evaluation.
• 🟠 Hypoglycemia with Concomitant Insulin or Sulfonylureas: Per FDA label, the risk of hypoglycemia is increased when Wegovy is used with insulin secretagogues (e.g., sulfonylureas) or insulin. Consider dose reduction of these agents. Symptoms include sweating, confusion, shakiness, and rapid heartbeat.
• 🟠 Acute Kidney Injury: FDA label reports acute kidney injury, sometimes requiring dialysis, in patients using GLP-1 receptor agonists, usually in association with dehydration from gastrointestinal side effects. Patients should maintain adequate hydration, especially during periods of vomiting or diarrhea.
• 🟠 Severe Allergic Reactions (Hypersensitivity): Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with semaglutide per FDA label. Wegovy is contraindicated in patients with known hypersensitivity to semaglutide. Discontinue immediately if hypersensitivity reactions occur and seek emergency care.
• 🟠 Diabetic Retinopathy Complications: In patients with type 2 diabetes and pre-existing diabetic retinopathy, rapid improvement in glycemic control has been associated with worsening retinopathy per FDA label (this effect has been observed across the semaglutide class). Prescribers should consider this risk in diabetic patients.
• 🟡 Heart Rate Increase: Mean increases in resting heart rate of 1–4 beats per minute were observed in Wegovy-treated patients in STEP trials per FDA label. The clinical significance of this finding is not established, but patients with known cardiac conditions should be monitored.
• 🟡 Suicidal Behavior and Ideation: FDA label states that depression, suicidal ideation, or suicidal behavior has been reported in patients treated with weight management products. Monitor for new or worsening depression or suicidal thoughts, especially in patients with a history of depression or mental illness.

Managing Side Effects

Nausea

Nausea is the most commonly reported reason for dose delays or discontinuation per STEP trial data. The FDA-approved dose escalation schedule — increasing the dose every 4 weeks over 16–20 weeks — was specifically designed to reduce nausea severity. Per the FDA label, the dose escalation can be extended if nausea is not tolerated. Practical strategies include eating smaller, more frequent meals; choosing bland, low-fat foods (crackers, toast, rice); avoiding lying down immediately after eating; and staying well hydrated. If nausea is severe and persistent, discuss anti-nausea medications with your prescriber.

Constipation

Constipation is reported in up to 24% of patients per FDA labeling and may persist throughout treatment. Because semaglutide slows gastric motility, proactive measures are important. Gradually increasing dietary fiber (vegetables, whole grains, legumes) and fluid intake to at least 8 cups of water daily is widely documented in clinical practice guidance. Gentle physical activity can support bowel regularity. If constipation is severe or accompanied by abdominal pain, notify your prescriber, as this can occasionally mimic more serious conditions.

Vomiting

Vomiting occurred in up to 24% of patients in STEP 1 (Wilding et al., NEJM 2021). Prolonged vomiting can lead to dehydration and electrolyte imbalance, which in turn increases the risk of acute kidney injury per FDA label. Maintain hydration with small, frequent sips of water or electrolyte solutions. If you cannot keep fluids down for more than 24 hours, seek medical attention. Your prescriber may recommend temporarily staying at your current dose rather than escalating, per FDA label guidance.

Diarrhea

Diarrhea reported in approximately 30% of STEP 1 participants is typically transient but can contribute to dehydration. Avoiding high-fat, greasy, or heavily spiced foods may reduce episodes. Staying well hydrated is critical. The FDA label notes that dehydration from gastrointestinal side effects has been associated with acute kidney injury in patients using GLP-1 receptor agonists, making fluid replacement a priority.

Injection Site Reactions

The FDA-approved prescribing information instructs patients to rotate injection sites with each weekly injection among the abdomen, thigh, or upper arm. Using a new needle with each injection, allowing the pen to reach room temperature before injecting (approximately 30 minutes out of the refrigerator), and avoiding injecting into areas that are bruised, red, or irritated can reduce local reactions. Do not inject into muscle or a vein.

Hair Loss

Hair thinning reported in STEP trials is generally attributed to telogen effluvium — a temporary form of hair shedding triggered by significant physiological stress such as rapid weight loss — rather than a direct pharmacological effect of semaglutide, as discussed in the FDA label. Adequate protein intake (to support hair follicle health during weight loss) and consultation with a dermatologist may be appropriate. Hair regrowth typically occurs as weight stabilizes, though this timeline varies.

Fatigue

Fatigue reported in approximately 11% of patients in STEP trials may be related to reduced caloric intake, altered meal timing, or the body's adaptation to lower energy availability. Ensuring nutritional adequacy — particularly adequate protein and micronutrient intake — is important. Fatigue that is severe, sudden, or accompanied by other symptoms (such as yellowing of skin or eyes, or abdominal pain) should be evaluated by a prescriber promptly, as it can occasionally signal more serious conditions including pancreatitis or liver issues.

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