Evidence review

Semaglutide long-term side effects

By David Chen·Editor·Reviewed September 2026

What the label approves¹

SELECT is the trial behind one of Wegovy’s approved uses. The injection is indicated, with a reduced-calorie diet and more physical activity:

To reduce the risk of major adverse cardiovascular (CV) events (CV death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established CV disease and either obesity or overweight.

That sentence is the claim FDA approved, and this page makes no other claim about the heart. The label adds, in its mechanism section, “The exact mechanism of semaglutide in CV risk reduction in adults has not been established.” What follows is what the same trial recorded about side effects over more than three years.

The longest trial: SELECT²

SELECT enrolled adults aged 45 or older with a BMI of 27 or more, established cardiovascular disease — a previous heart attack, stroke or symptomatic peripheral arterial disease — and no diabetes. Their mean age was 61.6, and 72.3% were men. They were randomized 1:1 to semaglutide 2.4 mg weekly or placebo, climbing to the full dose over 16 weeks.

Follow-up averaged 39.8 months, and people were on the assigned treatment for an average of 34.2 months. By week 104, about 77% of those still taking semaglutide were on the 2.4 mg dose. Permanent early discontinuation, for any reason, reached 26.7% on semaglutide and 23.6% on placebo.

One limit shapes everything below. The label says SELECT’s safety data collection “was limited to serious adverse events (including death), adverse events leading to discontinuation, and adverse events of special interest.”¹ It is a long record of serious harms and of reasons people stopped — not a full count of every mild side effect over three years.

What SELECT recorded²

The authors write that serious adverse events related to gastrointestinal disease, acute kidney failure, pancreatitis, cancers or psychiatric disorders were not more frequent with semaglutide than with placebo. A later analysis by body size found lower rates of serious adverse events on semaglutide in every BMI group, and more discontinuation the lower the starting BMI.³

The label reports several smaller signals from the same trial:¹

• Hip and pelvis fractures were more common on semaglutide in women — 1% (24 of 2,448) against 0.2% (5 of 2,424) — and in people 75 or older, 2.4% (17 of 703) against 0.6% (4 of 663).
• Kidney stones (urolithiasis): 1.2% against 0.8%, serious in 0.6% against 0.4%.
• Serious low blood sugar in people without diabetes: 3 episodes on semaglutide against 1 on placebo, and 2.3% (2 of 87) against 0% (0 of 97) among people with a history of bariatric surgery.
• Bilirubin at three or more times the upper limit of normal: 0.3% against 0.2%.

Two years: STEP 5⁴

STEP 5 was a weight-loss trial that ran twice as long as STEP 1: 304 adults without diabetes, 104 weeks. Gastrointestinal adverse events, mostly mild to moderate, were reported by 82.2% on semaglutide against 53.9% on placebo over the two years. Unlike SELECT, it reports everyday side effects like these, not only serious ones — but over two years rather than four. The weight results are on semaglutide results by month.

The label’s warnings¹

Wegovy’s current warnings, from section 5 of the label:

• Thyroid C-cell tumors — the boxed warning, from rodent studies, with human relevance not determined (the warning, verbatim).
• Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing forms, observed with GLP-1 receptor agonists.
• Acute gallbladder disease — in the weight trials, gallstones in 1.6% against 0.7%.
• Hypoglycemia, especially with insulin or a sulfonylurea.
• Acute kidney injury from dehydration, mostly after nausea, vomiting or diarrhea.
• Severe gastrointestinal reactions — 4.1% against 0.9% — and not recommended in severe gastroparesis.
• Hypersensitivity, including anaphylaxis and angioedema.
• Diabetic retinopathy complications in people with type 2 diabetes.
• Heart rate increase — a mean of 1 to 4 beats per minute at rest.
• Pulmonary aspiration during general anesthesia or deep sedation (surgery).
• Never share a FlexTouch pen between patients.

One warning is gone. The label’s change log lists Suicidal Behavior and Ideation (section 5.10) as removed, dated 01/2026 — the history is on semaglutide and mood. Separately, post-approval reports include pancreatitis sometimes resulting in death, ileus, intestinal obstruction and severe constipation including fecal impaction; the label notes such reports come from “a population of uncertain size,” so they carry no rate. The common reactions, each with its placebo rate, are on semaglutide side effects.

Long-term side effects of Ozempic⁵

Ozempic is the same molecule at diabetes doses of up to 2 mg, and its label carries the same core warnings — thyroid C-cell tumors, pancreatitis, gallbladder disease, kidney injury from dehydration, severe gastrointestinal reactions, hypersensitivity, pulmonary aspiration — plus diabetic retinopathy complications and low blood sugar with insulin or a sulfonylurea. Its longest trials are in people with type 2 diabetes: SUSTAIN 6, 3,297 people observed for a minimum of two years, and FLOW, 3,533 people with chronic kidney disease followed for a median of 41 months. How the two labels differ in other ways is on Ozempic vs Wegovy.

What long-term data does not exist

• Very little randomized data past four years. SELECT’s time-to-event figures stop at 48 months “because of the limited number of patients in the trial after 48 months,” and its weight analysis runs to week 208.²
• No complete count of mild side effects over years. SELECT collected serious events, events that led to stopping, and events of special interest; STEP 5 reports everyday side effects, but over two years.
• Little on younger people without heart disease. Every SELECT participant was 45 or older with established cardiovascular disease, and 27.7% were women; the authors list both as limitations.
• No answer yet on thyroid tumors in humans. The label says it is unknown whether semaglutide causes them in humans, and that routine calcitonin tests or thyroid ultrasound are of uncertain value for catching them early.¹
• No long-term study of the eye in diabetes. The label states: “The effect of long-term glycemic control with semaglutide on diabetic retinopathy complications has not been studied.”
• Little on the highest dose. The 7.2 mg dose was studied in 72-week trials, and the label counts 578 people who took it for at least a year.
• Nothing at all on compounded semaglutide. Every figure on this page comes from the approved products.

What this means for a compounded vial

This page reports what the trials and labels recorded; it is not a personal risk assessment, and whether to start, continue or stop semaglutide is a decision for a prescriber. See the medical disclaimer.