Ozempic (semaglutide) has well-documented short-term side effects like nausea and diarrhea, but the long-term picture is more complex. After a year or more of use, the drug carries a meaningful cardiovascular benefit, a real but modest risk of stomach-related complications, and emerging questions about muscle loss, bone health, nutrient deficiencies, and mood changes. Here’s what the evidence shows so far.
Cardiovascular Protection
The clearest long-term benefit is a reduction in heart attacks, strokes, and cardiovascular death. The SELECT trial, which followed over 17,600 people with heart disease and a BMI of 27 or higher for more than three years, found that semaglutide reduced major adverse cardiovascular events by 20%. This is the strongest outcome data for the drug and a major reason clinicians prescribe it beyond blood sugar control. Notably, these participants did not have diabetes, meaning the heart benefit appears to come from the drug itself and the weight loss it produces, not just from better blood sugar management.
Gastroparesis and Digestive Risks
The most discussed long-term gastrointestinal concern is gastroparesis, a condition where the stomach empties too slowly, causing persistent nausea, bloating, vomiting, and abdominal pain. A large retrospective study published in BMJ Open Gastroenterology found that gastroparesis occurred at a rate of 6.5 per 1,000 person-years among semaglutide users. That’s roughly three times higher than an alternative weight-loss medication (bupropion-naltrexone) and about six times higher than rates seen after sleeve gastrectomy surgery.
Among semaglutide formulations, Ozempic specifically had the highest gastroparesis rate at 7.2 per 1,000 person-years, compared to 3.7 per 1,000 for the oral tablet version. To put that in perspective, for every 1,000 people taking Ozempic for a year, roughly 7 would develop gastroparesis. That’s a small but real risk, and it’s worth knowing that GLP-1 drugs work partly by slowing stomach emptying, so this complication is a direct extension of the drug’s mechanism.
Muscle Loss During Weight Loss
Any significant weight loss, whether from medication, surgery, or dieting, takes some muscle with it. The concern with Ozempic is whether the speed and degree of weight loss tips the balance too far toward muscle loss, particularly in older adults. Research shows that semaglutide-induced weight loss does reduce lean mass alongside fat mass, though some studies suggest the ratio of lean mass to total body weight actually improves, meaning you lose proportionally more fat than muscle.
Whether this translates into sarcopenia (a clinically meaningful loss of muscle strength and function) remains unresolved. Researchers have repeatedly flagged higher risk in older adults and people with existing health conditions, but there is no definitive evidence yet showing that semaglutide causes sarcopenia at higher rates than other forms of equivalent weight loss. Resistance training during treatment is widely recommended to preserve muscle, though long-term data on how well that works in practice is still limited.
Bone Density and Fracture Risk
Bone loss is a known consequence of rapid weight loss from any cause. With semaglutide, the picture is concerning but not yet conclusive. A 20-week pilot trial in older adults found no statistically significant bone density changes with semaglutide compared to lifestyle changes alone. However, a longer and larger trial found measurably lower bone density at the hip and lumbar spine in the semaglutide group versus placebo.
The most striking finding comes from the SELECT trial’s long-term follow-up: adults aged 75 and older taking semaglutide had nearly five times the incidence of hip and pelvic fractures compared to placebo. For younger adults, the expected bone loss from a typical 5% weight loss on semaglutide falls in the range of 0.5% to 1%, which is within the margin of error for bone density scans and below what’s considered clinically meaningful. But for older adults already at fracture risk, this deserves serious attention.
Nutrient Deficiencies
Eating significantly less food for months or years creates an obvious risk: not getting enough vitamins and minerals. A large analysis of over 480,000 adults on GLP-1 drugs found that 4% developed anemia from nutritional deficiency, 3.2% had iron deficiency, and 2.6% had B vitamin deficiency. A smaller study that tracked actual food intake found the problem was even more pronounced. Among 69 GLP-1 users, 72% consumed less than the recommended amount of calcium, 64% fell short on iron, and only 1.4% met vitamin D recommendations.
These deficiencies develop gradually, which makes them easy to miss. They can cause fatigue, weakness, nerve problems (from B12 deficiency), and worsened bone health (from low calcium and vitamin D), compounding the bone density concerns already associated with the drug. A daily multivitamin and periodic blood work to check levels of iron, B vitamins, and vitamin D can help catch problems early.
Thyroid Cancer Concerns
Ozempic carries an FDA boxed warning about thyroid tumors based on rodent studies showing increased rates of medullary thyroid cancer. In humans, the evidence is more reassuring. A large observational study found no statistically significant increase in overall thyroid cancer risk among GLP-1 users. There was an apparent spike in thyroid cancer diagnoses during the first 12 months, but this elevated signal disappeared after the first year, and the most likely explanation is detection bias: people starting these drugs are simply getting more medical attention, including more thyroid ultrasounds. By 12 months, 2.1% of GLP-1 users had received a thyroid ultrasound compared to just 1.5% of people on other diabetes medications. More screening naturally finds more incidental thyroid nodules. The FDA warning remains in place as a precaution, and the drug is still contraindicated for people with a personal or family history of medullary thyroid cancer.
Eye Health in People With Diabetes
Early clinical trials of semaglutide raised a flag about worsening diabetic retinopathy, the eye damage caused by long-standing high blood sugar. This likely happens because rapid blood sugar improvement can temporarily stress blood vessels in the retina that have adapted to high glucose levels. However, a large real-world study comparing over 30,000 semaglutide users to a similar number of people on another GLP-1 drug found no difference in rates of sight-threatening diabetic retinopathy over roughly two years of follow-up. As a class, GLP-1 drugs do not appear to increase the risk of serious diabetic eye disease compared to older diabetes medications. If you have existing retinopathy, your doctor may monitor your eyes more closely when starting treatment, but long-term data has been largely reassuring.
Mood and Mental Health
This is perhaps the most unsettled area. GLP-1 receptors exist throughout the brain, including in regions involved in reward and motivation, so the drug’s effects aren’t limited to appetite. Some patients report a flattened emotional state, describing reduced pleasure from food, social interactions, and activities they previously enjoyed. This goes beyond the expected reduction in food cravings into something closer to anhedonia, a general inability to feel pleasure.
The research points in different directions. A 2024 study in Scientific Reports found that people with obesity on GLP-1 drugs had a slightly elevated risk of anxiety and suicidal behavior and nearly double the risk of major depression compared to controls. A 2025 paper suggested that people with a genetic predisposition toward low dopamine function may be especially vulnerable to depression and suicidal ideation on these drugs. One case report described a 42-year-old woman who developed severe delusions and attempted self-harm three weeks after starting Ozempic, with symptoms resolving after she stopped the medication.
On the other hand, a 2024 study led by researchers at the University of Pennsylvania found that GLP-1 users without pre-existing mental health conditions were no more likely to develop depression or suicidal thoughts than controls, and actually showed a small but statistically significant reduction in depressive symptoms. That study was funded by Novo Nordisk, the maker of semaglutide, which is worth noting. Both the FDA and the European Medicines Agency have reviewed the evidence on suicide risk and deemed the drugs safe, though monitoring continues. If you have a history of depression or mood disorders, this is worth discussing before starting treatment.