Ozempic (semaglutide) is generally well tolerated, but long-term use carries several risks beyond the nausea and digestive upset that most people experience in the first weeks. Some of these effects emerge months or even years into treatment, and a few are serious enough to warrant the drug’s strongest FDA warning label. Here’s what the evidence shows so far.
Persistent Digestive Problems
Nausea, vomiting, and diarrhea are the most common side effects of Ozempic at any stage. For most people, these symptoms ease as the body adjusts. But for a subset of users, the drug’s core mechanism, slowing how quickly your stomach empties, can tip into a more lasting condition called gastroparesis. This is when the stomach takes far too long to move food into the small intestine, causing chronic nausea, bloating, vomiting, and early fullness that doesn’t resolve on its own.
A Cleveland Clinic analysis found that people with type 2 diabetes who took GLP-1 drugs like Ozempic had a significantly increased risk of being diagnosed with gastroparesis starting at six months and continuing through at least two years of use. The risk remained elevated even after researchers controlled for other factors that can cause slow stomach emptying, like diabetes itself. Not everyone who feels sluggish digestion on Ozempic has gastroparesis, but if vomiting or severe bloating persists beyond the dose-adjustment period, it’s worth investigating.
Gallbladder Disease
Rapid weight loss from any cause increases the risk of gallstones, and Ozempic is no exception. When you lose weight quickly, the liver releases more cholesterol into bile, which can crystallize in the gallbladder. Clinical trials of semaglutide have consistently flagged gallbladder-related events, including gallstones and inflammation of the gallbladder (cholecystitis), as a notable side effect. The risk rises with higher doses and faster weight loss. If you develop sudden, intense pain in the upper right side of your abdomen, especially after eating, that’s the classic sign.
Kidney Injury From Dehydration
Ozempic doesn’t appear to damage the kidneys directly, but its gastrointestinal side effects can cause enough fluid loss to trigger acute kidney injury. A pharmacovigilance analysis published in Frontiers in Endocrinology identified 2,670 cases of acute kidney injury linked to GLP-1 drugs. Among those cases, 45% required hospitalization. The mechanism is straightforward: persistent nausea and vomiting lead to dehydration, and dehydrated kidneys can’t filter blood properly. The risk is higher if you’re also taking blood pressure medications that affect kidney function, such as ACE inhibitors or ARBs.
Staying well hydrated matters more on Ozempic than it might otherwise. If you’re vomiting frequently or unable to keep fluids down for more than a day, that’s a situation that needs prompt attention, not just for comfort but to protect your kidneys.
Eye Complications in People With Diabetes
One of the more counterintuitive findings from semaglutide trials is that the drug can temporarily worsen diabetic eye disease. In the SUSTAIN-6 trial, 3.0% of participants on Ozempic experienced retinopathy complications (including bleeding in the eye or the need for laser treatment) compared to 1.8% on placebo. This gap was much larger among people who already had retinopathy before starting the drug: 8.2% on Ozempic versus 5.2% on placebo.
This “early worsening” phenomenon isn’t unique to Ozempic. It happens whenever blood sugar drops rapidly after a long period of poor control. The blood vessels in the retina, already damaged by years of high glucose, react poorly to the sudden change. The Ozempic label now includes a warning about this. If you have existing diabetic eye disease, your doctor will likely want to monitor your eyes more closely during the first year of treatment.
Bone Density Loss During Weight Loss
When you lose a significant amount of weight, you lose some bone along with the fat and muscle. This is a known consequence of any major weight loss, but emerging data suggest semaglutide may accelerate the process. A trial comparing semaglutide to placebo found significantly lower bone density at the hip and lower spine in the semaglutide group, along with higher levels of bone turnover markers, the chemical signals that indicate bone is being broken down faster than it’s being rebuilt.
The concern is most acute for older adults. In the large SELECT cardiovascular outcomes trial, which followed participants for over 40 months, adults aged 75 and older taking semaglutide had nearly five times the incidence of hip and pelvic fractures compared to those on placebo. A smaller pilot study in older adults with obesity found that while the difference in whole-body bone density wasn’t statistically significant after 20 weeks, the semaglutide group consistently trended toward lower density and higher bone breakdown. Weight loss itself correlated directly with pelvic bone loss. If you’re older or already at risk for osteoporosis, resistance training and adequate calcium and vitamin D intake become especially important while on the drug.
The Thyroid Cancer Warning
Ozempic carries the FDA’s most serious label, a boxed warning, about the risk of thyroid C-cell tumors. In animal studies, semaglutide caused thyroid tumors at doses comparable to what humans take, and the risk increased with both dose and duration. Whether this translates to humans remains genuinely uncertain. The drug is contraindicated for anyone with a personal or family history of medullary thyroid carcinoma or a condition called Multiple Endocrine Neoplasia syndrome type 2.
A recent large study analyzing real-world data offers some reassurance. Overall, there was no statistically significant increase in thyroid cancer diagnoses among people starting GLP-1 drugs. During the first 12 months, diagnoses were elevated, but researchers at the Mayo Clinic attributed this largely to detection bias: people starting Ozempic were significantly more likely to receive thyroid ultrasounds (2.1% versus 1.5% of people on other diabetes medications by 12 months), which catches pre-existing cancers that would otherwise go unnoticed. After the first year, the elevated risk disappeared entirely. Still, the boxed warning remains because the animal data is concerning enough that regulators aren’t willing to rule out the possibility.
Mental Health Effects
Early reports raised concerns that GLP-1 drugs might increase the risk of suicidal thoughts or depression. The FDA took this seriously and conducted one of the most thorough safety reviews in recent memory. Their meta-analysis covered 91 placebo-controlled trials with nearly 108,000 patients and found no increased risk of suicidal ideation, self-harm, depression, anxiety, or psychosis. A separate real-world study using insurance claims data from over 2.2 million people reached the same conclusion.
Based on this evidence, the FDA has requested removal of the suicidal behavior warning from GLP-1 drug labels, concluding that the totality of evidence does not support a causal link. Some people do report mood changes or reduced interest in food-related pleasure while on these medications, but these experiences haven’t translated into measurable psychiatric harm at a population level.
Muscle Loss and Body Composition
Any time you lose weight rapidly, a portion of that loss comes from lean muscle rather than fat. Studies of semaglutide for weight loss suggest that roughly 30% to 40% of total weight lost can be lean mass, which is comparable to other forms of calorie-restricted weight loss but concerning given how much total weight people lose on the drug. Losing muscle affects your metabolism, physical strength, and long-term ability to maintain weight loss. This is why most clinicians now emphasize high-protein diets and regular strength training for anyone on Ozempic, particularly those using it primarily for weight management rather than blood sugar control.
Pancreatitis Risk
Acute pancreatitis, a sudden and painful inflammation of the pancreas, has been reported in people taking Ozempic and remains listed as a warning on the label. The overall incidence in clinical trials was low, but the consequences are serious enough that it’s worth knowing the signs: severe abdominal pain that radiates to your back, nausea, and vomiting that feels different from the typical GI side effects. If you’ve had pancreatitis before, the risk-benefit calculation for staying on the drug shifts meaningfully.