Tesofensine vs Semaglutide: A Head-to-Head Comparison

In this article, we will closely examine Tesofensine and Semaglutide, two different classes of drugs used to manage weight and type 2 diabetes. We will delve into their indicated uses, mechanisms of action, mode of administration and side effects.
Klara Hatinova

Klara Hatinova

Klara is postgraduate researcher in experimental psychology at the
University of Oxford.

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What are tesofensine and semaglutide?

Tesofensine and semaglutide are two different types of drugs that have demonstrated efficacy in obesity management.

Tesofensine was initially developed for treating Parkinson’s Disease and Alzheimer’s Disease. Since 2019, it has not been studied for dementia, but serendipitously, weight loss was reported across many subjects taking tesofensine. Due to this, tesofensine is now in phase III clinical trials for obesity management [1].

Semaglutide is the most known weight loss drug, marketed under the brand names Ozempic for type 2 diabetes and Wegovy for weight loss [2].

Similarities and differences between tesofensine and semaglutide

Indicated conditions: tesofensine vs semaglutide

Tesofensine was initially developed to be used in Alzheimer’s and Parkinson’s Disease. However, it has more promising outcomes in treating obesity and weight loss than in Alzheimer’s or Parkinson’s Disease since patients treated with tesofensine lost weight [1].

Semaglutide is used for weight loss, but also for type 2 diabetes. The Wegovy formulation of semaglutide is primarily indicated for weight loss, whereas Ozempic is primarily indicated for type 2 diabetes. Nonetheless, Ozempic can also be prescribed off-label for weight loss [3].

Tesofensine has not yet been studied in diabetes patients, and there is a subtle difference in the conditions that tesofensine and semaglutide can treat. Tesofensine is still under investigation and is not yet approved in many countries.

Mode of administration: tesofensine vs semaglutide

Semaglutide is available in both injectable and oral forms. Injectable semaglutide is taken weekly, and semaglutide tablets must be taken daily.

Tesofensine is only available as an oral tablet and must be taken once a day.

Mechanism of action: tesofensine vs semaglutide

Tesofensine and semaglutide work very differently.

Tesofensine works by inhibiting the reuptake of monoamine neurotransmitters including serotonin, dopamine, and norepinephrine, thereby increasing their levels in the brain [4]. This is similar to the action of many antidepressants. This action is believed to reduce appetite, reduce pleasure derived from food and increase metabolism, leading to weight loss [5].


On the other hand, semaglutide mimics the role of glucagon-like peptide-1 (GLP-1), a critical peptide for weight loss released from the small intestine. By mimicking the effects of natural GLP-1, semaglutide stimulates insulin release, reduces blood sugar and promotes satiety.

Side effects: tesofensine vs semaglutide

Tesofensine, a triple monoamine reuptake inhibitor, has been associated with:

  • dry mouth
  • nausea
  • constipation
  • hard stools
  • diarrhea
  • insomnia.

Due to its effects on noradrenalin, tesofensine can also increase blood pressure and heart rate when taken for longer periods of time at high doses [6]. These side effects make it unsuitable for patients with pre-existing cardiovascular complications [7].

On the other hand, semaglutide, which mimics the role of GLP-1, more commonly leads to gastrointestinal side effects. These include:[8]

  • nausea
  • vomiting
  • diarrhea
  • abdominal pain
  • constipation
  • decreased appetite
  • heartburn

More serious side effects are rare. Nonetheless, the span from stomach pain, swelling, vision changes and even diabetic retinopathy or thyroid carcinoma [9, 3, 10, 11]. For a more detailed analysis of the side effects of semaglutide, you can read our blog about the side effects of semaglutide vs tirzepatide.

Always consult with a healthcare professional for medical advice if you are taking tesofensine and experience any of these side effects.

Summary: Tesofensine vs semaglutide for type 2 diabetes

To summarise, in diabetes and weight loss, semaglutide remains the first-line treatment prescribed by healthcare professionals.

Both tesofensine and semaglutide are drugs for managing type 2 diabetes, although they work through different mechanisms, and so cause different side effects.

You should consult with your healthcare professional, who can advise you on the pros and cons of the drug profile when weighing the pros and cons of your individual condition.

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Klara Hatinova

Klara Hatinova

Klara is a postgraduate researcher in experimental psychology at the University of Oxford. She has worked across a spectrum of hot topics in neuroscience, including her current project measuring reinforcement learning strategies in Parkinson’s disease. Previously, she studied the efficacy of psilocybin as a therapy for critical mental health conditions and examined molecular circadian rhythms of migraine disorders. She completed her undergraduate degree in Neuroscience at the University of Glasgow and participated in a year abroad at the University of California, where she worked on a clinical trial for spinal cord injury.