Unexpected GLP-1 Side Effects with Ozempic, Wegovy and MANY Other Drugs

GLP-1 agonists remain among the most sought after drugs in the pharmacy. Doctors prescribe them for both type-2 diabetes and weight control. Semaglutide, sold under the names Ozempic, Wegovy and Rybelsus, is revolutionizing blood sugar and obesity treatment. But new side effects keep emerging. A new study in JAMA Ophthalmology (June 5, 2025) reports that people with type-2 diabetes using such GLP-1s appear to be at greater risk for neovascular age-related macular degeneration (AMD). That is the wet form of AMD. In this article, we will explore some other unexpected GLP-1 side effects. We will also point out how many other popular medications surprise both the FDA and health care professionals with unexpected side effects that can take a long time to be discovered.

AMD = an Unexpected GLP-1 Side Effect:

By now you are very familiar with the term GLP-1 RAs, even if you can’t remember what that stands for: glucagon-like peptide-1 receptor agonists. Most people have shortened that mouthful to GLP-1 and recognize drugs such as semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Victoza, Saxenda) and tirzepatide (Mounjaro, Zepbound). In truth, tirzepatide is both a GLP-1 RA and a GIP-1 receptor agonist. Please don’t ask me to explain the glucose-dependent insulinotropic polypeptide (GIP) activity of tirzepatide.

As successful as these drugs may be at helping people control blood glucose and lose weight, new side effects keep emerging. The latest unexpected GLP-1 side effect to show up is the wet form of age-related macular degeneration (JAMA Ophthalmology (June 5, 2025).

The authors of this report introduce their research this way:

“Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in older adults in Western populations. It is characterized by the progressive deterioration of central high-resolution vision, which is essential for daily activities, such as reading and driving. As of 2020, AMD affected approximately 196 million individuals globally, with projections suggesting an increase to 288 million individuals by 2040. In the US alone, AMD accounts for 8.7% of all cases of blindness.”

These researchers point out that in two clinical trials of semaglutide, there was a slightly higher risk of diabetic retinopathy among patients taking the medication than in the placebo group. That, of course, seems counterintuitive. One might anticipate that taking a drug that controls diabetes would reduce the risk of eye problems such as diabetic retinopathy or wet age-related macular degeneration (nAMD).

The authors reinforce this idea:

“Given that GLP-1 RAs can effectively and consistently reduce insulin resistance in patients with diabetes, these agents were anticipated to reduce the risk of nAMD in patients with diabetes through this mechanism. However, our analysis revealed the opposite: patients with diabetes who were exposed to GLP-1 RAs had a substantially higher risk of being diagnosed with nAMD, with a shorter time to diagnosis, compared with propensity-matched patients who were unexposed. These findings should be put into context of the known literature, as there have been numerous reports of unexpected worsening of diabetic retinopathy following a rapid reduction in blood glucose levels, occasionally resulting in permanent visual impairment in patients with insulin-dependent diabetes.”

“Our findings expand on the growing body of literature raising concerns regarding the potential ocular safety of systemic GLP-1 RA therapy in patients with diabetes.”

The two-fold increase in wet AMD was most evident in people using these drugs for the longest period of time. While the absolute risk is low, diabetes specialists and ophthalmologists should be vigilant for this potentially serious complication.

Other Unexpected GLP-1 Side Effects:

Most people are aware of common complaints associated with drugs like semaglutide and tirzepatide: nausea, vomiting, diarrhea, constipation abdominal distress, heartburn and flatulence. Drug companies warn about such adverse reactions.

The biggest problem with clinical trials designed to get FDA approval is that they 1) may not last long enough to pick up delayed drug complications and 2) may not ask about unexpected side effects. That’s why we always review the official prescribing information for “Postmarketing Experience.”

The FDA often requires an introduction to this section that goes something like this in the case of semaglutide:

“The following adverse reactions have been reported during post-approval use of semaglutide, the active ingredient of OZEMPIC. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.”

Some of the side effects that were not picked up during some semaglutide clinical trails include:

• Ileus [when the intestinal tract stops moving normally]. This can lead to some serious complications, especially if a patient requires anesthesia and surgery. You can read about stomach paralysis associated with semaglutide at this link.
• Pulmonary aspiration [when stomach contents are inhaled into the lungs during anesthesia or endoscopy]. This is a very serious medical emergency.
• Suicidal ideation. We find it fascinating that there is no mention of suicidal thoughts in the official prescribing information for Ozempic. The same exact medicine, Wegovy, comes with this warning:
  • “Suicidal behavior and ideation have been reported in clinical trials with other weight management products. Monitor patients treated with WEGOVY for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue WEGOVY in patients who experience suicidal thoughts or behaviors. Avoid WEGOVY in patients with a history of suicidal attempts or active suicidal ideation.”
• Hair loss. This is not listed as a potential side effect with Ozempic but is listed in the official prescribing information for Wegovy.
• Dizziness. This potential side effects is not listed for Ozempic, but is listed at 8% for people taking Wegovy. Remember, both of these drugs are semaglutide.

You can learn more about some unexpected GLP-1 side effects at this link:

“Are Hair Loss or Colitis Side Effects of Wegovy and Ozempic?”

In that article you will discover some astonishing anomalies. Why, for example, did patients getting placebo shots in a clinical trial for Ozempic report a 1.9% incidence of diarrhea while those receiving placebo injections in the Wegovy trial reported diarrhea 16-19% of the time?

That is about a 10-fold difference. In both instances the participants were getting nothing, nada, zip. Placebos in both cases! No one at the FDA has been able to explain this anomaly to my satisfaction.

Other Drugs With Unexpected Side Effects:

Paradoxical Effect of Diphenhydramine:

Antihistamines like Benadryl (diphenhydramine or DPH) often make people drowsy. No surprise. That is why so many nighttime pain relievers contain DPH. Think Advil PM, Aleve PM, Tylenol PM, etc. But some people experience paradoxical excitation or restless leg syndrome (RLS) after taking diphenhydramine. You can read more about this unexpected drug side effect at this link.

Antidepressants and Suicidal Ideation:

Antidepressants such as fluoxetine (Prozac), paroxetine (Paxil) or sertraline (Zoloft) belong in a class called SSRIs (selective serotonin reuptake inhibitors). The first SSRI was Prozac, approved in 1987. Hardly anyone is surprised if such a medication causes anxiety or insomnia. Psychological side effects seem consistent with a drug that affects the brain.

What did surprise the drug company, psychiatrists and the FDA were reports that such drugs might cause suicidal thoughts or actions. It seemed counterintuitive that antidepressants might trigger “suicidal ideation.” We have been warning about this unexpected drug reaction for many decades. It took the FDA until 2004 to warn about this worrisome complication. You can read about the sad saga at this link.

Antidepressants and Bleeding:

Most doctors and patients do not associate SSRI antidepressants with bleeding problems. But 19 years after Prozac entered the market, there was an article in CNS Drugs (2006).

The investigators reported:

“A literature search identified four studies of SSRI use and risk for upper gastrointestinal bleeding and a further two studies of SSRI use and bleeding in general, including upper gastrointestinal bleeding. The available evidence indicates quite convincingly that SSRI use may play a causal role in upper gastrointestinal bleeding and that these drugs may act synergistically with other bleeding risk-increasing medications such as NSAIDs or low-dose aspirin…Patients should be informed about the likelihood of possible upper gastrointestinal bleeding and high-risk patients should be followed closely.”

Part of the delay in recognizing unexpected drug side effects is because our medical system is fragmented. Psychiatrists prescribe antidepressants but they rarely see people with serious digestive distress. Gastroenterologists see people with bad bellyaches, but may not associate a hemorrhage in the stomach with an antidepressant. When the right hand doesn’t know what the left hand is doing, patients can suffer. Uncoordinated care can lead to complications from many medications.

Antidepressants, Sleeping Pills, Anti-Anxiety Drugs and ALS:

A research team at the Karolinska Institute in Sweden has just announced a worrisome drug complication (JAMA Network Open, June 4, 2025). The investigators analyzed health records from Sweden, comparing those of more than 1,000 people with amyotrophic lateral sclerosis, or ALS, with those of 5,000 healthy individuals. ALS is better known in the US as Lou Gehrig’s disease. It is a progressive neurodegenerative condition that gradually robs people of the ability to move.

According to the scientists, people who took anti-anxiety drugs, sleeping pills or antidepressants were at increased risk for developing ALS.  Among people who had ALS, those who had used such psychiatric drugs before diagnosis had the shortest survival time. The absolute risk of developing ALS is quite small, so increasing it even by 34 percent does not result in a high risk. It is worth noting, however, since there is no cure for ALS.

Fluoroquinolone Antibiotics and Tendon Rupture:

Antibiotics are generally considered to be quite safe. Doctors used to prescribe drugs like ciprofloxacin (Cipro)or levofloxacin (Levaquin) for sinus or urinary tract infections. One side effect of these medications that came as a big surprise was tendon rupture.

One reader shared this story:

“I took Levaquin to treat a lung infection. After five days I noticed tightness in my left Achilles’ tendon that hampered my ability to walk. Three days later my left ankle was so swollen I could hardly hobble. An MRI showed a completely severed Achilles’ tendon. I needed surgery and then spent six weeks in a wheelchair.”

Who would guess that a snapped Achilles’ tendon could be the consequence of treating bronchitis with an antibiotic?

PPIs and Fractures:

Hundreds of drugs have unexpected side effects. Physicians once prescribed proton pump inhibitors very widely. Now, PPIs such as esomeprazole (Nexium 24HR) and omeprazole (Prilosec OTC) can be purchased over the counter.

It is unlikely that the manufacturers of this class of medicines imagined that PPIs would be linked to fractures. Because these heartburn drugs are so effective at suppressing acid, they may interfere with the absorption of certain nutrients such as calcium. Theoretically this could contribute to weakened bones.

A systematic review and meta-analysis published in Rheumatology International (Nov. 2018) concluded:

“This meta-analysis suggests that PPI user[s] have a 26% increased risk of hip fracture as compared to non-PPI user[s]. Physicians should take caution in prescribing PPI to patients who are at increased risk of hip fracture.”

The doctors who deal with patients’ heartburn symptoms usually aren’t consulted if a patient breaks a hip. The orthopedic surgeons who fix broken hips may not link such fractures to medication taken for reflux. You can read about other unexpected side effects of proton pump inhibitor heartburn drugs at this link.

Final Words:

It can take a long time for the FDA to warn the public about unexpected drug side effects. Have you ever experienced an adverse reaction that you were not warned about? Please share your story in the comment section below. What about the diabetes and weight loss drugs semaglutide or terzepatide? Have you encountered unexpected GLP-1 side effects such as delayed gastric emptying or visual problems?

To help the FDA discover unanticipated reactions to prescription medications, such side effects should be reported to MedWatch (www.fda.gov/medwatch). If you think this alert about unexpected adverse drug reactions has value, please share it with friends and/or family members. Thank you for supporting our work.