Weight loss with drugs such as Ozempic (semaglutide), Wegovy (semaglutide), Zepbound (tirzepatide), and others is not only due to loss of fat but also muscle. Most people on these drugs are aware of this risk, and many try to forestall it by weight training and higher protein intake. But even some of those who exercise regularly report fatigue. The incidence of fatigue in people on GLP-1s is about 10%.
One reason for fatigue and other neurological symptoms is vitamin deficiencies. This often occurs due to significantly reduced food intake.
An analysis of drug-safety reports (pharmacovigilance study) found that Wernicke encephalopathy, a rare but severe and life-threatening vitamin B1 (thiamine) deficiency, occurs more often with GLP-1s than with other drugs. Most cases have occurred with semaglutide or tirzepatide. A separate analysis also found that Wernicke encephalopathy was disproportionately reported with semaglutide, tirzepatide, and other GLP-1s.
Reported cases typically involved prolonged nausea, vomiting, reduced food intake and rapid weight loss. Symptoms typically began within 2 weeks to 3 years, with an average of 6 months. Symptoms of Wernicke’s encephalopathy include nystagmus (jerky eye movements), inability to move the eyes, unsteadiness, and confusion. If untreated, thiamine deficiency leads to severe neurological disability or death.
Our bodies can store only 2–3 weeks’ worth of thiamine, so deficiency can develop quickly with severe intake reduction or persistent vomiting.
Thiamine is not the only deficiency I see in my patients taking GLP-1s. These deficiencies can cause a variety of neurological symptoms and often make migraines worse.
The Obesity Society and other organizations list nutrients at risk when food intake is significantly reduced: iron, calcium, magnesium, zinc, and vitamins A, D, E, K, B1, B12, and C.
An old diabetes drug, metformin, that can help with weight loss, is known to cause vitamin B12 deficiency in some patients, even without drastic weight loss.
Another class of drugs known to cause multiple deficiencies is proton pump inhibitors, drugs that are used to treat heartburn and ulcers. These include omeprazole (Prilosec), esomeprazole (Nexium), and others.
Heartburn or upset stomach occurs in up to 10% of patients on GLP-1s, and if these people are prescribed PPIs on top of GLP-1s, they are at a higher risk of multiple deficiencies.
I recommend that people on GLP-1s and PPIs take vitamin B12, a B-complex (other B vitamins), magnesium (as magnesium glycinate), CoQ10, vitamin D, and a multivitamin.
If you have persistent vomiting or difficulty eating, dizziness, weakness, headaches, numbness or tingling in your extremities, difficulty sleeping, anxiety, or any other new symptoms, see your doctor. New onset of confusion, trouble walking, or abnormal eye movements requires an emergency evaluation.
