December 29, 2025, 7:23 pm | Read time: 5 minutes
GLP-1 medications like semaglutide and tirzepatide are considered a medical breakthrough–but their common nickname, “weight loss injection,” overlooks the risks. From bowel obstruction to gallbladder issues and rare vision problems: Metabolism expert Prof. Norbert Stefan discusses the current state of research in a FITBOOK interview, clearly stating who truly benefits–and warns strongly against careless use in healthy individuals.
Who currently benefits the most from GLP-1 therapies–and which other patient groups could significantly benefit in the future–was explained by Prof. Dr. med. Norbert Stefan in the first part of the FITBOOK interview. The endocrinologist and diabetologist is among the leading experts on the clinical study landscape and mechanisms of GLP-1-based medications. With his research group at the University of Tübingen, he is internationally recognized for his work on cardiometabolic risks and modern therapeutic approaches. Part 2 now focuses on the risks all patients should be aware of before starting treatment. Special caution is advised for some patients.
»Feeling of fullness, nausea, vomiting, and constipation
FITBOOK: Mr. Stefan, what are the most common side effects of GLP-1-based medications?
Prof. Dr. med. Norbert Stefan: “The most common side effects affect the gastrointestinal tract. These include a feeling of fullness, as well as nausea, vomiting, and constipation. These symptoms mainly occur with too rapid dose escalation. Therefore, it is important to adhere to the recommended dosing schedules and increase the dose slowly. Maintaining adequate fluid intake is also crucial, as insufficient fluid intake can exacerbate constipation during GLP-1 therapy. In rare cases, it can even lead to a bowel obstruction. Studies from the U.S. show a slightly increased risk compared to other weight loss medications.”
»Formation of gallstones and pancreatitis favored under GLP-1 therapy
Which patients should be very cautious with these medications or avoid them altogether?
“We see indications that GLP-1-based preparations can slightly increase the risk of pancreatitis–an inflammation of the pancreas. Patients with relevant pre-existing conditions should be very cautious or avoid GLP-1 therapy altogether. The formation of gallstones also seems to be slightly favored under GLP-1 therapy. In very rare cases, this can lead to gallbladder inflammation–but this only affects a small group of patients.”
»Caution with pre-existing eye diseases
A recent study caused a stir about a possible increase in vision loss among semaglutide patients (FITBOOK reported). How do you assess this risk?
“It concerns a condition called NAION (non-arteritic anterior ischemic optic neuropathy, Ed.), which can severely impair vision. Several retrospective studies, mainly from the U.S., now suggest a slightly increased risk under GLP-1 therapy. Although this affects only a very small portion of patients–about four out of ten thousand (0.04 percent) treated with GLP-1 preparations over two years compared to two out of ten thousand (0.02 percent) who did not receive this therapy–it is enough to include corresponding warnings in the manufacturers’ product information. Especially with pre-existing eye diseases, an ophthalmological evaluation should be conducted before starting therapy.”
Prof. Dr. med. Norbert Stefan is an endocrinologist and diabetologist and holds the chair of clinical-experimental diabetology at the University Hospital Tübingen. He also heads the “Pathophysiology of Prediabetes” department at the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich. He has collaborated with manufacturers of GLP-1-based preparations, mostly in the context of scientific lecture events.
»In individual cases, depressive moods, no clear evidence for increased risk of depression or suicidality
There are also many reports of depressive moods or psychological side effects in the context of GLP-1 therapies. Should GLP-1 users expect this?
“This is a sensitive but important point. We know from bariatric surgery that significant weight loss–such as after gastric reduction–can trigger depressive symptoms or emotional crises in some people. For many, eating serves as a form of emotional self-regulation or reward. If this possibility is suddenly removed due to strong appetite reduction, it can be psychologically burdensome for certain patients. We also observe depressive moods in individual cases with GLP-1 medications. However, fortunately, there is no clear evidence yet for a significantly increased risk of depression or suicidality.”
“The Biggest Misconception About the Weight Loss Injection”
“Greatest Impact of GLP-1 Medications on These Patients”
»Concern about disproportionate muscle loss from GLP-1 not confirmed so far
What about muscle mass loss during GLP-1 therapy? What should users know or consider?
“Generally, people lose both fat and muscle mass with any form of weight reduction–whether through diet, bariatric surgery, or GLP-1 therapy. However, it is crucial that muscle strength is maintained. Studies show this very clearly. Initially, there was concern that GLP-1 medications could cause disproportionate muscle loss. This concern has not been confirmed so far. Rather, the muscle mass losses correspond to what is seen with other weight reductions. It is especially important for patients to stay active during therapy and engage in targeted strength training–this protects the muscles.”
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»Using GLP-1 medications as a lifestyle product? Not justifiable
In the U.S., there is a trend where even healthy and athletic people inject GLP-1-based medications in extremely small doses. Proponents of microdosing argue that it helps them stay fit preventively. What do you think of this? Is there any truth to it?
“This is a very critical development. The research clearly shows: The positive effects on cardiovascular and metabolic health mainly occur in people with pre-existing conditions–such as type 2 diabetes, overweight, and cardiovascular risk factors–or overweight and a history of heart attack or stroke. For healthy individuals without pre-existing conditions, there is currently no evidence that regular dosing or microdosing provides relevant health benefits–neither in preventing a heart attack nor in preventing Alzheimer’s or diabetes. Moreover, the described side effects also apply to low doses. Therefore, from a medical perspective, I do not consider it justifiable to use GLP-1 medications as a lifestyle product. They remain prescription drugs that must be used under medical supervision.”