Helen Ding
Helen Ding is an intern at Cosmos. She is a biomedical science graduate completing a master's degree in journalism at the University of Melbourne.
Semaglutide, the active ingredient in Ozempic, has been hailed as the new magic pill for weight loss. But is it safe and what are the real risks beyond loose skin and “Ozempic face” – the gaunt ageing effect of drastic weight loss?
What is semaglutide and how does it work?
Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that is prescribed to patients with type 2 diabetes and for weight management in patients who are overweight or obese. It is dispensed as either an anti-diabetic (Ozempic) or an anti-obesity (Wegovy) medication, with the latter available at a higher dosage. Of the 5 plus million Americans prescribed semaglutide in 2023, almost 4 in 10 were taking it for weight management.
GLP-1 RAs are administered via weekly subcutaneous (under the skin) injection and work by mimicking the effects of glucagon-like peptide-1 – a hormone produced by the intestine that makes us feel full after eating.
In the pancreas, GLP-1 receptors promote the production of insulin (the hormone that lowers blood sugar levels) and suppress the production of glucagon (the hormone that raises blood sugar levels).
In the stomach, GLP-1 receptors slow gastric emptying – food moves slower through the digestive system, resulting in a prolonged feeling of fullness. In the brain, GLP-1 receptors suppress hunger cravings and reduce appetite.
Like any medication, however, semaglutide can cause side effects. See below for some that have been reported. If you are experiencing any side effects, please seek medical advice.
Common or mild side effects of semaglutide
Patients taking semaglutide often report experiencing abdominal pain, constipation, diarrhoea, nausea and vomiting. Other mild side effects include hypoglycaemia-induced symptoms, such as dizziness and fatigue.
Serious or long-term side effects of semaglutide
As semaglutide is a relatively new drug, research into the serious and long-term side effects are still underway. However, some studies have found increased risks of:
Erectile dysfunction
Erectile dysfunction is the inability to attain or maintain an erection sufficient for sexual intercourse. There is some evidence that semaglutide can increase the risk of erectile dysfunction in non-diabetic males. A study from earlier this year found that those who took semaglutide for weight loss were at a significantly higher risk of developing erectile dysfunction and hypogonadism (testosterone deficiency).
Deep vein thrombosis
Semaglutide may substantially increase the risk of blood clots and clotting-related conditions such as deep vein thrombosis. According to a 2021 meta-analysis, type 2 diabetic patients using semaglutide were at a 266% increased risk of developing deep vein thrombosis. Dehydration and diarrhoea (both common side effects of semaglutide) thicken the blood, leading to an increased risk of clotting.
Gastrointestinal adverse events
In addition to the common gastrointestinal effects listed above, a 2023 JAMA study found patients taking semaglutide may be more at risk for developing serious gastrointestinal conditions, such as gallbladder or biliary disease, pancreatitis (inflammation of the pancreas) and gastroparesis (delayed gastric emptying).
According to Ozempic prescribing information, GLP-1 RAs have been associated with gallbladder disease, including cholelithiasis (gallstones) and cholecystitis (redness and inflammation of the gallbladder), in both clinical trials and post-marketing studies. In type 2 diabetes trials, cholelithiasis was reported in 1.5% of patients and 0.4% of patients treated with 0.5 mg and 1 mg Ozempic respectively. In weight management trials, cholelithiasis was reported in 1.6% of Ozempic-treated patients compared with 0.7% of placebo-treated patients.
Intestinal obstruction or ileus is a severe gastrointestinal condition that has been linked to semaglutide use. Ileus prevents waste moving through the digestive track and can lead to partial or complete blockage of the intestines. An untreated obstruction can result in a rupture of the intestine, which can be fatal.
A 2020 study found that of 698 intestinal obstruction cases (reported between January 2007–2018), 216 cases (31%) involved a GLP-1 RA. The authors conclude that “intestinal obstructions were more than 4.5 times more frequently reported with incretin-based drugs [such as GLP-1 RAs] than with other diabetes drugs”. Another study found that for every 1,223 patients treated with GLP-1 RAs for a year, one additional case of intestinal obstruction may be expected.
Sudden blindness
Semaglutide may be associated with “non-arteritic anterior ischemic optic neuropathy (NAION)” – a form of “eye stroke” which causes sudden, painless vision loss in one eye. A JAMA Ophthalmology article from July found that patients treated with semaglutide had a higher risk of developing NAION compared with those treated with non-GLP-1 RA medications. Of 710 type 2 diabetics, 17 patients developed NAION in the semaglutide cohort compared with 6 in the non-GLP-1 RA cohort. Of 979 patients who were overweight or obese, NAION occurred in 20 individuals compared with 3 in the non-GLP-1 RA cohort. It is important to note that the research only shows a correlation, not causation – which requires future study to assess.
Suicidal ideation
While some research, including a recent JAMA Network study, found an association with suicidal thoughts, others seems to indicate that semaglutide users are slightly less likely to have suicidal thoughts than those not taking them.
Thyroid tumours
As with suicidal ideation, the research is not entirely clear on whether semaglutide treatment causes thyroid tumours. Although risk of thyroid C-cell tumours is listed in the prescribing information, a systematic literature review found that the “incidence of thyroid cancer in semaglutide-treated patients was less than 1%, suggesting no significant risk.”
Disclaimer
The content of this article does not constitute medical advice. Should you have concerns or wish to make changes to your semaglutide treatment plan, please consult your doctor or other qualified healthcare professional.
