Tesofensine Side Effects: Heart Rate, Blood Pressure, Insomnia, and Mood in Clinical Trials

The most common tesofensine side effects in clinical trials were dry mouth, nausea, constipation, diarrhea and insomnia, and it raised resting heart rate. In the 2008 phase 2 obesity trial in The Lancet, heart rate rose by about 7 beats per minute in the middle-strength arm at 24 weeks, while blood pressure did not rise significantly at the lower two strengths. Neuropsychiatric effects such as insomnia, anxiety and mood change are the other main concern, and in 2013 The Lancet published an expression of concern about how that trial reported adverse effects.

Tesofensine is a small molecule, not a peptide. This guide summarizes what the trials found, how strong the evidence is, and who should not use it.

Educational content for licensed healthcare professionals. Not medical advice; dosing and treatment decisions belong to the prescribing clinician.

What Tesofensine Is

Tesofensine (NS2330) is an oral triple monoamine reuptake inhibitor: it blocks the reuptake of noradrenaline, dopamine and serotonin. It was first studied in Parkinson's disease, where weight loss was among the observed effects [4], and was then developed for obesity. In overweight men it increased satiety and fullness and reduced prospective food intake [1]. It has a long elimination half-life, and its clearance is reduced by the strong CYP3A4 inhibitor itraconazole [2]. See the Tesofensine library page for background and our overview of emerging weight-loss compounds.

Tesofensine Side Effects: Evidence Table

What the Obesity Trial Found

The pivotal study was a 24-week, randomized, double-blind, placebo-controlled phase 2 trial in 203 adults with obesity at five Danish centers. Weight loss with the two higher strengths was roughly four to five times that of diet plus placebo. The most common adverse events caused by tesofensine were dry mouth, nausea, constipation, hard stools, diarrhea and insomnia. At 24 weeks, the two lower strengths showed no significant increase in systolic or diastolic blood pressure, but heart rate rose by 7.4 beats per minute in the middle arm. The authors said efficacy and safety needed confirmation in phase 3 [3].

In 2013, The Lancet issued an expression of concern about this paper [7], and the lead author published a correspondence titled "Under-reporting of adverse effects of tesofensine" [8]. Prescribers should read the original adverse-event data with that context in mind.

Heart Rate and Blood Pressure

Raised heart rate is the most consistent cardiovascular finding. In early Parkinson's disease (261 patients), decreased body weight and elevated heart rate were common in the highest arm [4]. In obesity, heart rate rose at 24 weeks [3].

The pattern fits the drug's noradrenergic action, which raises sympathetic tone. A small human trial tested a fixed combination of tesofensine and metoprolol (Tesomet) in hypothalamic obesity and found no significant heart-rate or blood-pressure differences from placebo; sleep disturbance, dry mouth and headache were more common, and one patient stopped because of worsened pre-existing anxiety [9].

Insomnia, Anxiety and Mood

A review of neuropsychiatric effects of centrally acting obesity drugs found insomnia to be the most common adverse effect of monoamine-targeting agents, including tesofensine, and noted that these drugs can also affect mood and anxiety [6]. In advanced Parkinson's disease, gastrointestinal and neuropsychiatric adverse events were more frequent than with placebo, especially at higher strengths [5]. Given the serotonergic, noradrenergic and dopaminergic actions, prescribers should treat mood change, anxiety, irritability and sleep loss as expected risks.

Who Should Avoid Tesofensine

• Uncontrolled hypertension, tachyarrhythmia, coronary disease, or heart failure.
• Current MAO inhibitor use, or other serotonergic or sympathomimetic drugs, given the triple reuptake mechanism.
• Strong CYP3A4 inhibitors, which increase tesofensine exposure [2].
• History of bipolar disorder, psychosis, severe anxiety, or suicidality.
• Pregnancy and breastfeeding, for which there are no data.

• Competitive athletes. Tesofensine is classified as an S6 stimulant on the WADA Prohibited List, banned in competition [10].

Monitoring Considerations for Prescribers

• Resting heart rate and blood pressure at baseline and at each follow-up.
• ECG in patients with cardiac history or palpitations.
• Mood, anxiety and sleep screening at baseline and at each visit, using a validated tool such as PHQ-9 or GAD-7.
• A full medication review for serotonergic drugs, stimulants, MAO inhibitors and CYP3A4 inhibitors.
• Remember the long half-life: adverse effects may persist for some time after stopping [2].

For general principles, see our weight-loss peptide safety guide.

Regulatory Status (October 2026)

Tesofensine is not FDA-approved. It is an investigational small-molecule drug, not a peptide, and it is not on the 503A Bulks List. It is not among the substances our FDA Peptide Status Tracker lists as under evaluation or scheduled for a PCAC meeting. A 2026 anti-doping study noted that it has been marketed online as a "dietary supplement" while still under regulatory review [10]; products sold that way are not legitimate drug sources.

Frequently Asked Questions

What are the most common side effects of tesofensine?

In the phase 2 obesity trial, the most common adverse events were dry mouth, nausea, constipation, hard stools, diarrhea and insomnia. Heart rate also rose.

Does tesofensine raise heart rate or blood pressure?

It raises heart rate; the obesity trial found about 7 beats per minute in the middle arm. Blood pressure did not rise significantly at the lower strengths in that trial, but animal studies show sympathetic increases in both.

Can tesofensine cause anxiety or depression?

Neuropsychiatric adverse events were more frequent than with placebo in Parkinson's disease, and insomnia is common. The 2013 expression of concern about adverse-event reporting is another reason to screen mood carefully.

Is tesofensine a peptide?

No. It is a small-molecule triple monoamine reuptake inhibitor taken orally. It is often grouped with peptides in weight-loss discussions but is chemically unrelated.

Is tesofensine FDA approved?

No. It is investigational and not approved by the FDA. Check the FDA Peptide Status Tracker for related compounding updates.

Newtropin does not prescribe, compound, or dispense. We connect licensed providers with licensed 503A compounding partners; prescribers can start at For Providers.

References

1. Sjödin A, et al. The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men. Int J Obes (Lond). 2010;34(11):1634-43. PubMed
2. Lehr T, et al. Semi-mechanistic population pharmacokinetic drug-drug interaction modelling of a long half-life substrate and itraconazole. Clin Pharmacokinet. 2010;49(1):53-66. PubMed
3. Astrup A, et al. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9653):1906-1913. PubMed
4. Hauser RA, et al. Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson's disease. Mov Disord. 2007;22(3):359-65. PubMed
5. Rascol O, et al. Tesofensine (NS 2330), a monoamine reuptake inhibitor, in patients with advanced Parkinson disease and motor fluctuations: the ADVANS Study. Arch Neurol. 2008;65(5):577-83. PubMed
6. Nathan PJ, et al. Neuropsychiatric adverse effects of centrally acting antiobesity drugs. CNS Neurosci Ther. 2011;17(5):490-505. PubMed
7. [No authors listed]. Expression of concern: effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet. 2013;381(9873):1167. PubMed
8. Astrup A, et al. Under-reporting of adverse effects of tesofensine. Lancet. 2013;382(9887):127. PubMed
9. Huynh K, et al. Randomized controlled trial of Tesomet for weight loss in hypothalamic obesity. Eur J Endocrinol. 2022;186(6):687-700. PubMed
10. Krug O, et al. Investigations into the metabolism and elimination of tesofensine in human urine. Drug Test Anal. 2026;18(9):1163-1173. PubMed