Drug Reference

Ozempic

semaglutide · Updated 2026-01-15 · Sources cited to FDA labeling

Ozempic (generic name: semaglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist administered as a once-weekly subcutaneous injection. Per its FDA-approved labeling (NDA 209637), Ozempic is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, and to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease.

How It Works

According to the FDA-approved Ozempic prescribing information, semaglutide is a GLP-1 receptor agonist that works by mimicking the action of naturally occurring GLP-1, an incretin hormone released from the gut after eating. The mechanism involves three primary pathways:

Glucose-Dependent Insulin Secretion

Semaglutide stimulates the pancreatic beta cells to release insulin, but only when blood glucose is elevated. This glucose-dependent action means the drug does not trigger insulin release during normal or low blood sugar states, per FDA labeling.

Glucagon Suppression

The drug suppresses glucagon secretion from pancreatic alpha cells in a glucose-dependent manner, reducing the liver's production of new glucose. This dual mechanism lowers both fasting and post-meal blood sugar levels, per FDA labeling.

Gastric Emptying & Appetite

Semaglutide slows the rate at which the stomach empties food into the small intestine and acts on appetite-regulating centers in the brain. FDA labeling notes this contributes to reduced caloric intake and the weight loss observed in clinical trials.

In the SUSTAIN-1 through SUSTAIN-5 trial program, semaglutide 0.5 mg and 1.0 mg once weekly produced statistically significant reductions in HbA1c compared to placebo and active comparators.

Side Effects by Week

Time Period Common Side Effects What Helps
Weeks 1–2
(0.25 mg starting dose per FDA labeling)		 Nausea (most frequent), decreased appetite, mild vomiting, injection-site reactions (redness, itching). Reported in ≥5% of patients in SUSTAIN trials. Eating smaller, low-fat meals; staying upright after eating; avoiding high-fat or spicy foods; rotating injection sites as directed in FDA labeling.
Weeks 3–4
(Still on 0.25 mg; dose escalation begins after 4 weeks per FDA labeling)		 Nausea may persist or begin to improve; diarrhea, constipation, and abdominal pain reported in clinical trials. Fatigue noted in some participants in SUSTAIN program. Increased hydration to manage diarrhea; fiber intake adjustments for constipation; consistent injection timing on same day each week per labeling instructions.
Months 2–3
(0.5 mg maintenance or escalation to 1.0 mg per FDA labeling)		 GI symptoms frequently decline in intensity. Belching, dyspepsia, and gastroesophageal reflux reported in SUSTAIN trials. Possible transient increase in GI effects at dose escalation. Continuing small meal strategies; over-the-counter antacids (discussed with prescriber); monitoring blood glucose as instructed by prescriber during dose change.
Long-Term
(≥6 months, ongoing use)		 GI effects typically stabilize. Hypoglycemia risk increases when combined with insulin or sulfonylureas, per FDA labeling. Possible modest heart rate increase noted in SUSTAIN-6. Injection-site reactions may continue. Regular follow-up with prescriber; monitoring for hypoglycemia symptoms; eye exams as FDA labeling warns of worsening diabetic retinopathy in patients with pre-existing retinopathy.

Most Common Side Effects

The following side effects were reported in ≥5% of patients receiving Ozempic in the SUSTAIN clinical trial program and are listed in the FDA-approved prescribing information:

  • Nausea: The most frequently reported adverse reaction across SUSTAIN-1 through SUSTAIN-5 trials, occurring in up to 20% of patients on 1.0 mg semaglutide versus 6% on placebo, per FDA labeling.
  • Vomiting: Reported in approximately 9% of patients receiving 1.0 mg semaglutide in SUSTAIN trials, compared to roughly 4% on placebo, per FDA labeling.
  • Diarrhea: Occurred in approximately 9% of 1.0 mg semaglutide recipients versus 7% on placebo in SUSTAIN trials, per FDA labeling.
  • Abdominal pain: Reported in approximately 7% of patients on 1.0 mg semaglutide in SUSTAIN trials, per FDA labeling.
  • Constipation: Reported in approximately 5% of patients on 1.0 mg semaglutide in SUSTAIN trials, per FDA labeling.
  • Decreased appetite: Noted as a GI-related adverse reaction in FDA labeling and observed across the SUSTAIN clinical program.
  • Dyspepsia (indigestion): Listed as a common GI adverse reaction in the FDA-approved Ozempic prescribing information.
  • Belching and flatulence: Reported in the SUSTAIN trial program and included in the FDA labeling as GI adverse reactions.
  • Injection-site reactions: Including redness, swelling, and itching at the injection site, reported in clinical trials and noted in FDA labeling.
  • Hypoglycemia (with insulin or sulfonylureas): FDA labeling states that when Ozempic is used in combination with insulin or insulin secretagogues, the dose of insulin or the secretagogue may need to be reduced to lower risk of hypoglycemia.

Serious Side Effects

The following serious adverse effects are identified in the FDA-approved Ozempic prescribing information and/or FDA safety communications. Contact a healthcare provider immediately if any of these occur.

  • ⚠️ [BOXED WARNING] Thyroid C-Cell Tumors: In rodent studies, semaglutide caused dose-dependent thyroid C-cell tumors. Per FDA boxed warning, it is unknown whether Ozempic causes thyroid C-cell tumors in humans. Ozempic is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
  • ⚠️ Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been reported with GLP-1 receptor agonists. FDA labeling instructs prescribers to discontinue Ozempic promptly if pancreatitis is suspected.
  • ⚠️ Diabetic Retinopathy Complications: In SUSTAIN-6, 3.0% of semaglutide-treated patients versus 1.8% of placebo-treated patients experienced diabetic retinopathy complications (HR 1.76; 95% CI, 1.11–2.78). FDA labeling recommends monitoring patients with a history of diabetic retinopathy.
  • ⚠️ Acute Kidney Injury: FDA labeling reports postmarketing cases of acute kidney injury and worsening of chronic renal failure, sometimes requiring hemodialysis, usually associated with nausea, vomiting, diarrhea, and dehydration.
  • ⚠️ Hypersensitivity Reactions: Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported in postmarketing surveillance, per FDA labeling.
  • ⚠️ Heart Rate Increase: Mean increases in resting heart rate of 1–6 beats per minute were observed in semaglutide-treated patients versus placebo in SUSTAIN trials, per FDA labeling. Clinical significance in patients with preexisting cardiac conditions warrants prescriber awareness.
  • ⚠️ Hypoglycemia (severe): Severe hypoglycemia requiring assistance was reported in SUSTAIN-6 and other SUSTAIN trials when semaglutide was used with insulin or sulfonylureas. FDA labeling specifies dose adjustment guidance for concomitant use.
  • ⚠️ Cholelithiasis and Cholecystitis: Cases of gallstones and gallbladder inflammation have been reported in clinical trials and postmarketing experience with semaglutide, per FDA labeling.

Managing Side Effects

Nausea

Nausea is the most commonly reported adverse reaction with Ozempic, reported in up to 20% of patients receiving 1.0 mg in SUSTAIN trials per FDA labeling. The FDA-approved prescribing information notes that GI adverse reactions are often transient, particularly during dose escalation. The following strategies are consistent with general prescriber guidance and the slow dose-escalation schedule outlined in FDA labeling:

  • The FDA-recommended starting dose is 0.25 mg once weekly for 4 weeks — a non-therapeutic dose intended solely to improve GI tolerability before escalation to 0.5 mg, per labeling.
  • Eating smaller, bland, low-fat meals and avoiding foods known to exacerbate nausea (e.g., greasy, spicy foods) is commonly advised.
  • Remaining upright for at least 30–60 minutes after eating may reduce reflux-related nausea.
  • Injecting on the same day each week at the same time of day (with or without meals, per labeling) may help patients identify and anticipate timing of GI effects.

Vomiting and Diarrhea

Vomiting was reported in approximately 9% and diarrhea in approximately 9% of patients on 1.0 mg semaglutide in SUSTAIN trials, per FDA labeling. Dehydration is a recognized risk, which FDA labeling links to downstream acute kidney injury in postmarketing reports.

  • Maintaining adequate fluid intake is critical when experiencing repeated vomiting or diarrhea.
  • FDA labeling advises that Ozempic should be used with caution in patients with renal impairment, due to reports of acute kidney injury associated with GI-related dehydration.
  • Patients should notify their prescriber if vomiting or diarrhea is severe or persistent, as dose interruption or adjustment may be warranted.

Constipation

Constipation was reported in approximately 5% of patients on 1.0 mg semaglutide in SUSTAIN trials, per FDA labeling. Slowed gastric emptying — a known pharmacological effect of semaglutide per FDA labeling — contributes to this effect.

  • Adequate dietary fiber and fluid intake are commonly recommended adjuncts.
  • Patients experiencing prolonged or painful constipation should consult their prescriber before using any laxatives or stool softeners, particularly given semaglutide's effects on GI motility.

Injection-Site Reactions

Injection-site reactions (redness, swelling, bruising, itching) are listed in the FDA-approved Ozempic prescribing information. Per FDA labeling, Ozempic is injected subcutaneously in the abdomen, thigh, or upper arm.

  • Rotating injection sites within and between the three recommended regions can reduce localized skin reactions, per standard subcutaneous injection technique.
  • Allowing the pen to reach room temperature before injection may reduce injection discomfort, as noted in the Ozempic Instructions for Use (IFU) supplied with FDA-approved labeling.
  • Injecting into scar tissue, tattoos, or areas of lipodystrophy should be avoided, per labeling.

Diabetic Retinopathy

Per SUSTAIN-6 (Marso SP et al., N Engl J Med. 2016;375:1834–1844), diabetic retinopathy complications occurred in 3.0% of semaglutide-treated patients versus 1.8% of placebo-treated patients (HR 1.76; 95% CI, 1.11–2.78). FDA labeling recommends monitoring patients with a history of diabetic retinopathy.

  • Patients with pre-existing diabetic retinopathy should have baseline and follow-up ophthalmologic examinations as directed by their prescriber.
  • The mechanism is not fully established, but rapid improvement in glycemic control has been historically associated with early worsening of retinopathy in diabetes care literature.

Hypoglycemia Risk with Combination Therapy

FDA labeling states that the risk of hypoglycemia is increased when Ozempic is co-administered with insulin or insulin secretagogues (e.g., sulfonylureas). In SUSTAIN-6, confirmed symptomatic hypoglycemia was reported in both treatment arms in patients on background insulin or sulfonylurea therapy.

  • Per FDA labeling, a dose reduction of insulin or the secretagogue should be considered when initiating Ozempic.
  • Patients should be instructed in hypoglycemia recognition and treatment (e.g., glucose tablets or fast-acting carbohydrates) by their prescriber.

Cost and Access in 2026

Cash Price (Without Insurance)

As of early 2026, the list price for a one-month supply of Ozempic (one pen, 4 doses) is approximately $935–$1,000 per pen for the 0.5 mg/dose and 1 mg/dose pens, and approximately $935–$1,000 for the 2 mg/dose pen, depending on pharmacy. Prices vary by retailer and region. GoodRx and similar discount programs may reduce cash prices at participating pharmacies.

Novo Nordisk Savings Program

Novo Nordisk offers the Ozempic Savings Card for eligible commercially insured patients, which may reduce monthly out-of-pocket costs to as low as $25 per prescription (terms subject to change; visit NovoNordisk.com or the Ozempic official website for current eligibility requirements). Income-based assistance is available through the Novo Nordisk Patient Assistance Program (NovoCare®) for qualifying uninsured or underinsured patients.

Insurance Coverage Notes

Coverage varies by plan. Medicare Part D covers Ozempic for its FDA-approved indication of type 2 diabetes management and cardiovascular risk reduction, though formulary tier placement affects copay amounts. As of 2025–2026, Medicare does not cover semaglutide solely for weight loss (Wegovy is a separate FDA-approved product). Prior authorization is commonly required. Medicaid coverage varies by state.

Compounded Semaglutide

The FDA placed semaglutide on its drug shortage list, which previously permitted compounding pharmacies to produce compounded semaglutide. The FDA removed semaglutide injection from the shortage list in early 2025. Compounded versions are not FDA-approved and lack the safety, efficacy, and manufacturing quality data of the FDA-approved Ozempic product. Patients should consult their prescriber and verify current FDA shortage list status before considering compounded alternatives.

Frequently Asked Questions

Per FDA labeling (NDA 209637), Ozempic is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, and to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) in adults with type 2 diabetes and established cardiovascular disease. Ozempic is not FDA-approved for weight loss — that indication belongs to Wegovy (semaglutide 2.4 mg), a separate FDA-approved product.
Per FDA labeling, Ozempic is available in three pen configurations: a 0.25 mg or 0.5 mg/dose pen (2 mg/1.5 mL), a 1 mg/dose pen (4 mg/3 mL), and a 2 mg/dose pen (8 mg/3 mL). The prescribing information specifies a starting dose of 0.25 mg once weekly for 4 weeks, escalating to 0.5 mg once weekly, then optionally to 1 mg once weekly after at least 4 weeks, and further optionally to 2 mg once weekly after at least 4 additional weeks if additional glycemic control is needed.
Per FDA labeling and the Ozempic Instructions for Use, Ozempic is injected subcutaneously (under the skin) once weekly in the abdomen, thigh, or upper arm. The injection can be given at any time of day, with or without meals. The day of the week can be changed if needed, as long as the new injection is at least 2 days after the prior dose, per labeling. The needle is not included with the pen and must be purchased separately.
SUSTAIN-6 (Marso SP et al., N Engl J Med. 2016;375:1834–1844) was a cardiovascular outcomes trial involving 3,297 patients with type 2 diabetes at high cardiovascular risk. The trial demonstrated a statistically significant 26% relative risk reduction in major adverse cardiovascular events (MACE) with semaglutide versus placebo (HR 0.74; 95% CI, 0.58–0.95; p<0.001 for noninferiority; p=0.02 for superiority). This evidence forms the basis for the cardiovascular risk reduction indication in FDA labeling.
Per FDA labeling, Ozempic is contraindicated in patients with: (1) a personal or family history of medullary thyroid carcinoma (MTC); (2) patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2); and (3) known serious hypersensitivity to semaglutide or any excipients of the product. FDA labeling also warns against use in patients with a prior serious hypersensitivity reaction to the product. Use in patients with type 1 diabetes or for treatment of diabetic ketoacidosis is not recommended, as Ozempic is not a substitute for insulin.
Per FDA labeling, there are limited human data on semaglutide use in pregnancy. Animal reproduction studies showed adverse developmental outcomes at clinically relevant doses. The labeling states that Ozempic is not recommended during pregnancy and advises patients to discontinue the drug at least 2 months before a planned pregnancy, given semaglutide's long half-life of approximately one week. Patients should discuss pregnancy planning with their prescriber.
Per FDA labeling, Ozempic has been studied in combination with metformin, sulfonylureas, SGLT-2 inhibitors, thiazolidinediones, and insulin (basal insulin) across SUSTAIN trials. FDA labeling specifically notes that when initiating Ozempic in patients already on insulin or insulin secretagogues, a dose reduction of those agents should be considered to reduce the risk of hypoglycemia. Drug interactions with orally administered medications may occur due to semaglutide's effect on gastric emptying, per labeling.
Per the FDA-approved Ozempic prescribing information and Instructions for Use, if a dose is missed, the missed dose should be administered as soon as possible within 5 days after the missed dose. If more than 5 days have passed, the missed dose should be skipped and the next dose administered on the regularly scheduled day. The once-weekly schedule should then be resumed. The dosing day may be changed if at least 2 days (48 hours) have elapsed since the last injection.
Per the FDA-approved Ozempic prescribing information and Instructions for Use: unused (new) pens should be stored in the refrigerator at 36°F–46°F (2°C–8°C). After first use, the pen may be stored at room temperature (59°F–86°F / 15°C–30°C) or in the refrigerator for up to 56 days (8 weeks). Pens should not be frozen, and should be protected from heat and direct light. If a pen has been frozen, it must not be used, per labeling.

This page is for informational purposes only and does not constitute medical advice. Consult your prescriber before making any medication decisions.

Sources
  • FDA label: Ozempic (semaglutide) injection, NDA 209637, revised 2023
  • SUSTAIN-6 trial: Marso SP et al., N Engl J Med. 2016;375(19):1834-1844
  • SUSTAIN-1 through SUSTAIN-5 trials: Novo Nordisk clinical program
  • FDA Drug Safety Communication: GLP-1 receptor agonists and thyroid C-cell tumors
  • ClinicalTrials.gov: NCT01720446 (SUSTAIN-6)
  • American Diabetes Association Standards of Care 2024 (referenced for context only; not a labeling source)

This site provides general information only and does not constitute medical advice. All content is sourced to FDA labeling, NIH publications, or peer-reviewed clinical trials. Always consult your prescriber before making any medication decision.