Are Weight Loss Medications Safe?
For patients with questions related to the potential side effects of Semaglutide (Ozempic, Wegovy) and Tirzepatide (Mounjaro, Zepbound).
Dr. Ryan Oughtred, ND, CBEOct 29/ 2025There are 3 effective treatments for weight loss:
Behaviour Therapy
Medication
Surgery
Of these, medications are the treatment that have made the most rapid advances in the past decade or two, and patients now have 2 powerful medications available that have average weight reductions of >%12 on average, more than doubling what could be expected from the first generations of obesity medications or behaviour therapy. I will only be discussing these 2 medications:
Semaglutide (Ozempic, Wegovy)
Tirzepatide (Mounjaro, Zepbound)
With the benefits of newer, 2nd generation obesity medications becoming more known, I find myself spending less time discussing the benefits of these treatments with patients and more time discussing and addressing concerns around side effects or adverse events. This is understandable - it’s hard to get an effect from a medication without side effects, and these medications are relatively new. Patients are also right to point out that pharma has a history of introducing new medications before the risks and benefits are fully known.
What are the potential downsides and risks of weight loss medication?
Because the adverse events associated with Semaglutide (Wegovy) and Tirzepatide (Zepbound) are similar I will discuss them together.
Gastrointestinal adverse events (nausea, diarrhea, vomiting, constipation) are the most frequent side effects, with nausea being the most common.
Adverse events are usually mild to moderate in intensity and are transient in nature, diminishing after 3-6 months for most individuals.
Adverse events are not a given, and many are preventable with good management and planning - this is something I help my patients with. I prefer to take a pro-active approach to addressing many of these adverse events in advance, rather than deal with them reactively as they come.
Many of the adverse events seen with obesity medications are also seen as a result of active, significant weight reduction. Symptoms like headaches, dizziness, constipation, dry skin, low energy, or feeling cold can be a result of weight loss through intensive behavioural treatment, without medication. There is an increase rate of gall stones and gastrointestinal concerns with weight loss that is also unrelated to medication for instance. Seeing an obesity professional could help you prevent and manage side effects more confidently and understand which aspects of treatment are related to issues you might experience along the way.
Drawing primarily from the STEP and SURMOUNT trial data (Obesity Trials), as well as SUSTAIN and SURPASS trials (Diabetes Trials), here are some of the adverse events associated with Semaglutide and Tirzepatide:
Adverse Events (Side Effects)
Nausea - 45-90% (10-15% placebo)
Diarrhea - 60% (5-15% placebo)
Constipation - 25-50% (5-10% placebo)
Dyspepsia (indigestion) - 10-40% (5% placebo)
Abdominal Pain - 10-15% (5% placebo)
Headache - 5-15% (placebo 5-15%)
Dizziness - 5-15% (placebo 5%)
Eructation (belching) - 5-15% (placebo 0.5%)
Hair loss - 5-15% (placebo 1%)
Hypoglycemia (low blood sugar) - 1-5% (placebo 0-1%)
Injection Site Reactions 0.5% (placebo 0.5%)
Serious Adverse Events
Gall Bladder Disorders: 2-5% (0-1.5% placebo)
Predominately Cholelithiasis (gallstones).
Severe GI disorders (including obstruction, severe gastroparesis, severe gastroenteritis): 1-6% (0-2% placebo)
Acute pancreatitis: 0 - 0.1% (0 - 0.05% placebo)
Neither medication demonstrates increased risk of medullary thyroid carcinoma or pancreatic cancer. A risk for medullary thyroid carcinoma is observed in rodent studies, but it appears that GLP-1 physiology in rodents is differentiated enough in humans that we have not seen this issue arise in human trials.
It is unknown whether patients with diabetes experience a slightly elevated risk of diabetic retinopathy, and whether that increased risk is short term only. The SUSTAIN-6 trial demonstrated a 1% increase beyond placebo. The FOCUS trial is currently underway and there should be more evidence on this in the future.
The effects of these medications during pregnancy are unknown.
Discontinuation due to adverse events occurs in roughly 8% of patients vs roughly 4% for placebo.
Patients who have discontinued treatment previously often succeed with treatment when retrying therapy at a later date in the future.
Cost
At the time of writing this, Semaglutide and Tirzepatide can range anywhere from $100 - $1,000/ month in Canada. I discuss costs in other posts, but I will say that there are ways to curb costs to some extent.
Semaglutide (Ozempic) will be off patent in Canada and available in generic form starting in January 2026, which might reduce costs significantly.
Life Long Treatment
It deserves mention that weight related medications are recommended for long term use, not short term use. This is the same for weight related treatments - if the treatment stops, the weight comes back. I think it makes sense to consider this factor in your informed consent process. That said, I am also encouraging of individuals trying a treatment on for size and if it doesn’t work for them, then they can stop. You don’t have to know whether you will keep using the treatment long term before you start taking it, but I encourage you to consider the issue.
Contraindicated in Pregnancy
The effects of these medications are unknown in pregnancy and it is recommended patients avoid these medications for at least 2 months prior to conception.
Other Potential Concerns
The above adverse events listed are drawn from randomized controlled trials (RCT’s), which are the gold standard in medicine. Unfortunately, they are industry sponsored studies; as we have seen in the past, this can often lead to results that are biased toward the treatment in question. That said, they are the best evidence we have at this time. The only way to get rid of that bias is to run non-industry sponsored trials to assess safety and efficacy, but we do not have these kinds of studies at this time. This leaves us in a position where we are observing the populations of individuals taking these medications and the ones that are not, and trying to draw conclusions in that way - this is not ideal, and we must be careful in how much weight we give to information found in this way. That said, we can skeptically watch what some of this data is telling us. Here are some of the concerns drawn from such data:
Observational data has suggested a small increase in retinal and optic nerve related problems which are unproven and possibly related to aggressive weight reduction rather than GLP-1 medication use. These concerns are related to Semaglutide, so patients who remain worried about these rare events may prefer tirzepatide, which does not show similar safety signals in current real-world and pharmacovigilance data. (13)
Post-marketing surveillance has identified a signal for depression and suicidality with semaglutide that was rare (<1%) and was not demonstrated in any of the initial randomized trials. This signal has not been seen with Tirzepatide. Recent cohort studies and meta-analyses suggest that there is no additional increase psychiatric risk of these medications at this time, and some observational studies demonstrate psychiatric benefits from taking GLP-1ra medication (15, 16, 18).
Loss of muscle mass and bone density, in elderly patients in particular, is a concern with weight loss treatments in general (regardless of medication use). The greater the weight loss, the greater the risk for these concerns, which warrants individualized monitoring (DXA, Fitness Assessment) and supportive interventions (Strength Training) for at risk and elderly patients. Obesity studies are largely focused on middle aged patients, elderly patients should be managed more closely with individualized treatment.
Renal failure, worsening of kidney disease or nephritis are reported concerns, but these signals are small and are not thought to be significant at this time; moreover, there are longer term renal protective effects in patients taking these medications that likely counterbalance the risk v benefit decision for taking these medications in most patients. Patients engaging in rapid weight reduction place additional stress on their kidneys, regardless of whether they are taking medication; more moderate approach to weight reduction coupled with thoughtful monitoring is advised for patients with concerns around kidney health.
Severe hypoglycemia is rare with both drugs and occurs almost exclusively in patients on concomitant insulin or sulfonylureas; rates are comparable to placebo in RCTs.
Both medications have an effect of slowing gastric emptying, Tirzepatide in particular, which may reduce the absorption of oral medications, for example in contraceptives; this has led to recommendations for alternative or barrier contraception during dose escalation. These concerns are well-documented in real-world pharmacovigilance and post-marketing surveillance, but are not considered major safety risks for most patients.
Life threatening allergies are exceedingly rare and are not a reported concern with these medications in either RCT or observational data.
“Are medications like Ozempic or Mounjaro safe?”
The general consensus is yes, they are safe and fairly well tolerated over time. Their primary side effects (Nausea) are directly proportionate to their efficacy. Earlier versions of GLP-1ra medications did not lead to the same intensity of initial symptoms but they were also less effective.
But aren't these medications new? What if there are harmful effects of the drugs that have not surfaced yet?
This is a good question, as there are examples of medications that have been approved in the past that had to be removed from the market because of potential harms.
Patients have been taking GLP-1 receptor agonists for nearly two decades
Exenatide was first approved in 2005 and subsequent agents (liraglutide, dulaglutide, semaglutide, tirzepatide) introduced over the following years. Real-world registry and cohort studies show mean treatment duration of approximately 3 years, with some patients on therapy for up to 10 years or more. Treatment persistence and duration of treatment have increased over time as these agents have become more widely used for diabetes and obesity. Benefits and risks of this class of medications thus far have been similar and predictable.
Widespread use makes discovering rare events more likely
Semaglutide was approved in 2017 which led to a boom in the use of GLP-1ra medications. Tens of millions of people per year in North America alone have been taking this class of medications for roughly 5 years now. What this does is increase the sample size for observational studies to draw from, making it easier to spot rare adverse events in particular.
Fenfluramine is an example of an appetite suppressant that was approved in the 70’s, but was not removed from the market until the 90’s. In the early 90’s, a version of the drug that was combined with phentermine (Known as “Fen-Phen”) enjoyed a rapid increase in popularity for use in weight reduction in the USA. This increased adoption facilitated discovery that the drug was associated with valvular disease in a small group of patients. We have seen an increased adoption of Semaglutide since 2017 and there are likely more people that use GLP-1ra medications every year than the total amount of people that took Fen-Phen.
Adverse events can be discovered quickly
The drug Vioxx was approved in 1999 and within a year it was realized that the drug should not have been approved.
Current Science is Robust
Obesity medications are poised to generate revenues totalling >100 billion dollars per year. There are close to 100 Phase 3 RCT’s done to date on GLP-1ra medications. The efficacy of these medications is clear, and there is intense study in this area, with an explosion of research and spending on high quality research. These are well funded trials, which means they can be powerful enough to unearth safety concerns.
Obesity trials are longer and more sophisticated than they were in the past. In order for an obesity treatment to be deemed “effective” it must follow patients for a year, with some trials following patients for even longer, providing an opportunity for chronic adverse events to be detected.
Exploring the downsides to treatment is a necessary, and often undervalued step on the path toward change. I hope you found this helpful.
Have questions around how your health might benefit from treatment for weight? Contact me for an assessment and consultation.
Dr. Ryan Oughtred, ND, CBE1.
Tirzepatide Once Weekly for the Treatment of Obesity.
Jastreboff AM, Aronne LJ, Ahmad NN, et al.
The New England Journal of Medicine. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038.
2.
Once-Weekly Semaglutide in Adults with Overweight or Obesity.
Wilding JPH, Batterham RL, Calanna S, et al.
The New England Journal of Medicine. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183
3.
Smits MM, Van Raalte DH.
Frontiers in Endocrinology. 2021;12:645563. doi:10.3389/fendo.2021.645563.
4.
Evaluating the Safety Profile of Semaglutide: An Updated Meta-Analysis.
Rivera FB, Arias-Aguirre E, Aguirre Z, et al.
Current Medical Research and Opinion. 2024;40(9):1495-1514. doi:10.1080/03007995.2024.2383731
5.
Karagiannis T, Malandris K, Avgerinos I, et al.
Diabetologia. 2024;67(7):1206-1222. doi:10.1007/s00125-024-06144-1.
6.
Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.
Aronne LJ, Horn DB, le Roux CW, et al.
The New England Journal of Medicine. 2025;393(1):26-36. doi:10.1056/NEJMoa2416394.
7.
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.
Frías JP, Davies MJ, Rosenstock J, et al.
The New England Journal of Medicine. 2021;385(6):503-515. doi:10.1056/NEJMoa2107519.
8.
Aroda VR, Erhan U, Jelnes P, et al.
Diabetes, Obesity & Metabolism. 2023;25(5):1385-1397. doi:10.1111/dom.14990
9.
Tirzepatide for Obesity Treatment and Diabetes Prevention.
Jastreboff AM, le Roux CW, Stefanski A, et al.
The New England Journal of Medicine. 2025;392(10):958-971. doi:10.1056/NEJMoa2410819.
10.
Ren X, Hua H, Wu Y, et al.
Scientific Reports. 2025;15(1):24103. doi:10.1038/s41598-025-09807-0.
11.
Zaazouee MS, Hamdallah A, Helmy SK, et al.
Diabetes & Metabolic Syndrome. 2022;16(6):102511. doi:10.1016/j.dsx.2022.102511.
12.
Karagiannis T, Avgerinos I, Liakos A, et al.
Diabetologia. 2022;65(8):1251-1261. doi:10.1007/s00125-022-05715-4.
13.
Lakhani M, Kwan ATH, Mihalache A, et al.
American Journal of Ophthalmology. 2025;277:148-168. doi:10.1016/j.ajo.2025.05.007.
14.
Feier CVI, Vonica RC, Faur AM, Streinu DR, Muntean C.
International Journal of Molecular Sciences. 2024;25(8):4346. doi:10.3390/ijms25084346
15.
Tobaiqy M, Elkout H.
International Journal of Clinical Pharmacy. 2024;46(2):488-495. doi:10.1007/s11096-023-01694-7.
16.
GLP-1 Receptor Agonist Use and Risk of Suicide Death.
Ueda P, Söderling J, Wintzell V, et al.
JAMA Internal Medicine. 2024;184(11):1301-1312. doi:10.1001/jamainternmed.2024.4369.
17.
He L, Wang J, Ping F, et al.
JAMA Internal Medicine. 2022;182(5):513-519. doi:10.1001/jamainternmed.2022.0338.
18.
Mapping the Effectiveness and Risks of GLP-1 Receptor Agonists.
Xie Y, Choi T, Al-Aly Z.
Nature Medicine. 2025;31(3):951-962. doi:10.1038/s41591-024-03412-w.
19
Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes.
Perkovic V, Tuttle KR, Rossing P, et al.
The New England Journal of Medicine. 2024;391(2):109-121. doi:10.1056/NEJMoa2403347.
20
Ren Q, Zhi L, Liu H.
Drug Design, Development and Therapy. 2025;19:5645-5652. doi:10.2147/DDDT.S531778.