Tesofensine

What is tesofensine, and why is it not a peptide?

Peptides are formed by amino acids linked in a chain. Tesofensine, by contrast, is a small molecule with the chemical formula C17H23Cl2NO in the FDA’s substance registration system, also known by the code name NS2330; its salt forms (citrate, tartrate) are registered separately. ^[1] It is taken orally and is classified as a “triple monoamine reuptake inhibitor” that blocks the reuptake of norepinephrine, dopamine and serotonin at nerve terminals. ^[2]

For this reason tesofensine is grouped not with peptide drugs but with substances that act on the central nervous system: WADA lists tesofensine in the same section as sibutramine, under S6 Stimulants. ^[11] Doping researchers write that, while the drug is still at the regulatory review stage, it is marketed online as a dietary supplement for weight control and “metabolic support.” ^[7]

Development for Parkinson’s and Alzheimer’s disease

Tesofensine was first tried for neurological diseases. In the double-blind RCT in 261 people with early-stage Parkinson’s disease who were not receiving dopaminergic treatment, the difference in total UPDRS score versus placebo at week 14 was not significant at any of the three doses (−0.7, −1.3 and −1.7 points). Weight loss and heart rate increase were common at the highest dose; the most common adverse effects were constipation, insomnia and dry mouth. ^[5]

The notable weight loss in these studies led to the development of the drug for obesity. In a pooled analysis of four RCTs in people with Parkinson’s or Alzheimer’s disease (tesofensine 740, placebo 228 patients, 14 weeks, no weight-loss program), weight change was +0.5% in the placebo group and ranged from −0.5% to −2.8% at increasing doses. Heart rate changed by −0.4 on placebo and between +2.1 and +6.8 beats/minute in the tesofensine groups; no effect on blood pressure was seen. ^[4] This is a secondary result drawn from studies whose main purpose was not weight.

What has been shown in obesity?

The phase 2 obesity RCT published in a peer-reviewed journal was conducted at five obesity centers in Denmark; according to the ClinicalTrials.gov record, the trial began in September 2006 and was completed in September 2007, and its sponsor was the company that was developing the drug at the time. ^[15] After a two-week preparation period, 203 adults with a body mass index of 30–40 were given an energy-restricted diet and received once daily, for 24 weeks, one of three different tesofensine doses or placebo. The primary outcome was the percent change in body weight, and the analysis was done with all randomized participants who received at least one dose and had a measurement; 79% of participants completed the study. ^[2]

Source: phase 2 trial. ^[2] The most common adverse effects were dry mouth, nausea, constipation, hard stools, diarrhea and insomnia; no significant blood pressure increase versus placebo was seen at the two lower doses. The authors state that the results need to be confirmed by phase 3 trials. ^[2]

The Lancet expression of concern

In 2011 the Danish Health and Medicines Authority selected this study for a random inspection and found problems at two of the five centers. According to The Lancet’s 2013 expression of concern, three main points emerged from the inspection: delegation of the informed consent duty to non-physician staff at one center; questioning, in an earlier inspection, of the integrity of blinding (the investigators rejected this); and incomplete adverse event recording by the contract research organization. In particular, in participants who had previously experienced headache, migraine, stress or depression, these events had not been reliably recorded. The inspection report concluded that the published adverse event profile was not consistent with the actual course of the study. ^[3] In their July 2013 reply, the authors acknowledged that monitors had wrongly instructed investigators not to record headache, migraine, stress and depression as adverse events if they had also been experienced before randomization, and that these adverse events were under-reported in the published article at all centers. ^[16] The expression of concern appears for the article in the PubMed record; no retraction record appears. ^[3]

The phase 3 trial in Mexico and the license application

According to the developing company’s statements, its Mexican license partner ran a 24-week, placebo-controlled phase 3 trial in 372 patients with obesity; the company reports about 10% weight loss at the higher of two doses, no significant effect on blood pressure and a “small but statistically significant” heart rate increase. ^[9] The source of these results is company reports, and the placebo group result is not given in these reports.

The technical committee of the Mexican medicines authority gave a non-binding favorable opinion in February 2023. ^[9] However, in November 2024 the company announced that the authority had not approved tesofensine for the treatment of obesity. ^[8] According to the interim report dated August 2026, the license partner is continuing its application for approval; that is, as of that date the drug is not licensed in Mexico either. ^[9]

Heart rate, blood pressure and other side effects

The most consistent safety finding of tesofensine is a heart rate increase: a dose-dependent +2.1 to +6.8 beats/minute in the pooled analysis of the Parkinson’s and Alzheimer’s studies and +7.4 beats/minute at the medium dose in the obesity trial. ^{[4] [2]} The authors of the hypothalamic obesity trial summarize previous data as a heart rate increase at treatment doses and a mild and occasional blood pressure increase at high doses. To offset this effect, tesofensine was developed as a fixed-dose combination with metoprolol, a beta blocker that slows the heart rate. ^[6]

In the 24-week RCT of this combination in 21 adults with obesity due to hypothalamic damage (hypothalamic obesity), the additional weight change versus placebo was −6.3% (95% CI −11.3 to −1.3), and no heart rate or blood pressure difference was seen between the two groups. The primary outcome of the study was safety, and 18 patients completed 24 weeks. Sleep disorder (50% vs 13%), dry mouth (43% vs 0%) and headache (36% vs 0%) were more common in the combination group; in one patient with a prior history of anxiety and stress, anxiety worsened and treatment was discontinued. The developing company funded the study; some of the authors are employees, consultants or shareholders of the company. ^[6] The FDA granted this combination an orphan drug designation for Prader-Willi syndrome in 2021; a designation is not an approval, and the combination is not approved for this indication. ^[10]

Products containing tesofensine alone lack this offsetting component. People with a psychiatric diagnosis and those using beta blockers or MAO inhibitors were not included in the hypothalamic obesity trial; safety in these groups was not examined in this trial. ^[6] In the Parkinson’s trial too, insomnia and dry mouth were among the most common adverse effects. ^[5]

What do regulators say?

• FDA (US): In FDA records, an orphan drug designation for the tesofensine + metoprolol combination in Prader-Willi syndrome appears; the combination is marked “not approved” for this indication. ^[10] According to the 2026 article by doping researchers, tesofensine is still at the regulatory review stage and has no full marketing authorization. ^[7]
• Mexico: The application was not approved in 2024; the process is ongoing as of August 2026. ^{[8] [9]}
• WADA: In the 2026 Prohibited List it is named in the S6 Stimulants section among specified stimulants; S6 substances are prohibited in-competition. ^[11] Researchers at a doping control laboratory have developed a validated method that detects tesofensine and its four main metabolites in urine. In six volunteers who took a product sold as a supplement once by mouth, the substance could be detected in urine for up to 500 hours, with marked differences between individuals. The authors also state that the recommended use is unlikely to produce a urine finding above the minimum reporting levels applicable to stimulants, and that the substance may be particularly relevant in weight-class sports and in disciplines where the power-to-weight ratio is decisive. ^[7]

For the evidence and safety monitoring of licensed obesity drugs:

What is the status of tesofensine in Türkiye?

The legal status of peptides and similar products: Are peptides legal? The meaning of the “for research purposes” label: What does “research peptide” mean?

Evidence table: claim, population and limits

Limits of this guide

This page summarizes published evidence and official documents on tesofensine; it contains no individualized dose, method of use, course length or product source. Tesofensine is not a licensed drug in any country; the products used in trials do not have the same quality assurance as products sold online. The regulatory status may change; the information on this page is valid as of October 2026.