Tesofensine: what it is, what the trials found, side effects and why it is not a peptide

Tesofensine is a synthetic small molecule, coded NS2330, that inhibits the presynaptic reuptake of three neurotransmitters: noradrenaline, dopamine and serotonin. It was developed by the Danish company NeuroSearch, initially with Boehringer Ingelheim, as a treatment for neurodegenerative diseases. When it proved ineffective for Parkinson’s and Alzheimer’s disease, the trials showed an unintended effect, weight loss, and NeuroSearch redirected it to obesity ^[1].

Is tesofensine a peptide? No. It has a molecular weight of about 328, roughly a tenth of a small peptide, and it is taken as a tablet or capsule. It appears on this site because peptide research suppliers sell it alongside peptides, often as a tesofensine peptide by loose association with the weight-loss category. Its pharmacology has nothing in common with GLP-1 drugs such as semaglutide or liraglutide, which act on a gut-hormone receptor; tesofensine acts on transporter proteins in the brain, in the same broad class as older appetite suppressants such as sibutramine. Saniona, which took over development after NeuroSearch, also combined it with the beta-blocker metoprolol under the name Tesomet ^[13].

The 2026 anti-doping literature describes tesofensine as still under regulatory review and marketed online as a dietary supplement promoted for weight management ^[14]. Whether sold as a supplement or as a research product, it is not a licensed medicine. See what research peptides are for what the research label means, bearing in mind that in this case the product is not a peptide at all.

By blocking the transporters that clear noradrenaline, dopamine and serotonin from synapses, tesofensine raises the levels of all three. A PET imaging study in people measured striatal dopamine transporter occupancy of 18% to 77% across daily doses of 0.125 to 1 mg at steady state, with a maximum achievable occupancy of about 80% and half of that reached at roughly 0.25 mg, or a plasma concentration of 4 ng/mL ^[10]. The authors concluded that the dose-dependent weight loss seen in trials was partly mediated by increased synaptic dopamine.

Rat studies point to which receptors matter downstream. In diet-induced obese rats, tesofensine’s suppression of feeding was almost completely reversed by an alpha-1 adrenoceptor blocker and partly reversed by a dopamine D1 receptor blocker, but not by blockers of alpha-2, D2, D3 or serotonin 2A/C receptors, so the appetite effect depends on indirect stimulation of alpha-1 and D1 pathways ^[11].

In people, the effect is mostly on appetite rather than energy burning. In a two-week study of 32 overweight or moderately obese men in a respiration chamber, tesofensine produced 1.8 kg more weight loss than placebo despite instructions to keep eating normally, increased ratings of satiety and fullness, raised 24-hour fat oxidation by 18 g, and increased energy expenditure only at night, by 4.6%, with no significant effect on total 24-hour energy expenditure ^[8]. A later analysis of the phase 2 obesity trial found that the rise in a composite satiety score at 12 weeks correlated with weight loss over 24 weeks, but that the satiety effect faded as weight loss progressed and returned to baseline after the drug was withdrawn ^[9].

The first signal came from the neurology trials. A 2008 meta-analysis of four randomised trials in Parkinson’s and Alzheimer’s disease, with 740 people on tesofensine and 228 on placebo for 14 weeks and no weight-loss programme, found weight changes of +0.5%, −0.5%, −0.9%, −1.8% and −2.8% on placebo and 0.125, 0.25, 0.5 and 1.0 mg respectively. In the obese subgroup, 32.1% of those on 1.0 mg lost at least 5% against 2.1% on placebo. Heart rate rose by up to 6.8 beats per minute but blood pressure did not change ^[2].

The phase 2 obesity trial, known as TIPO-1 and published in The Lancet in 2008, randomised 203 obese adults with a BMI of 30 to 40 at five Danish centres to tesofensine 0.25, 0.5 or 1.0 mg or placebo once daily for 24 weeks, with an energy-restricted diet. Weight fell by 4.5%, 9.2% and 10.6% on the three doses against 2.0% on placebo, and 79% of participants completed the trial. The authors suggested that 0.5 mg might produce twice the weight loss of drugs then approved ^[5]. This is the tesofensine results figure quoted on vendor sites, and it needs the context below.

In 2013, five years after publication, The Lancet issued an expression of concern about the trial ^[6], and the trial’s authors published a letter titled “Under-reporting of adverse effects of tesofensine” ^[7]. The published record therefore contains an acknowledged problem with the adverse-event reporting of the main efficacy trial. Anyone quoting the 10.6% figure should quote the correction alongside it.

The other completed efficacy study is in hypothalamic obesity, a rare form of weight gain caused by damage to the hypothalamus. In 2022, a randomised trial of Tesomet (tesofensine 0.5 mg with metoprolol 50 mg) in 21 adults found 6.3% more weight loss than placebo over 24 weeks, with 8 of 13 on Tesomet losing at least 5% against 1 of 8 on placebo. Eighteen patients completed the trial ^[13].

The Parkinson’s trials are worth describing because they show the drug’s original purpose and its limits. In early Parkinson’s disease, 261 people were randomised to 0.25, 0.5 or 1.0 mg or placebo for 14 weeks; none of the doses improved the total Unified Parkinson’s Disease Rating Scale score significantly, and decreased body weight and raised heart rate were common in the 1.0 mg group ^[3]. In advanced Parkinson’s with motor fluctuations, the ADVANS trial tested 0.125 to 1 mg for 14 weeks and found modest improvements at 0.5 mg and 0.25 mg on different measures but no clear dose-response, with gastrointestinal and neuropsychiatric adverse events more frequent than on placebo, especially at higher doses ^[4].

A separate crossover study examined abuse potential in 52 recreational stimulant users, comparing tesofensine with placebo, D-amphetamine, bupropion and atomoxetine. Tesofensine’s subjective effects were not significantly different from placebo and were lower than amphetamine on all primary measures, and the authors concluded its abuse potential was no greater than that of bupropion or atomoxetine ^[12].

Registered but unpublished studies include a NeuroSearch long-term safety trial in 140 obese patients completed in 2008 ^[15], and Saniona’s Tesomet trials in type 2 diabetes ^[16] and Prader-Willi syndrome ^[17]; two further Tesomet trials in Prader-Willi syndrome and hypothalamic obesity were withdrawn in 2022 before enrolling anyone. We found no completed tesofensine phase 3 trial on ClinicalTrials.gov or in the literature as of September 2026, and a 2009 review noted only that the FDA had endorsed a phase 3 programme ^[1]. Whatever happened to that programme, it has not produced a published phase 3 result.

Weight loss was measurable within two weeks in the respiration-chamber study ^[8] and the satiety effect peaked around 12 weeks and then declined in the 24-week trial ^[9]. Tesofensine is eliminated slowly: after a single 483 µg dose taken as a supplement, six volunteers had detectable urinary metabolites for up to 500 hours, about three weeks, with wide variation between individuals ^[14]. Slow elimination means blood levels build up over the first weeks of daily dosing and persist after stopping.

The obesity trial used 0.25, 0.5 and 1.0 mg once daily by mouth for 24 weeks ^[5]. The neurology trials used 0.125 to 1.0 mg daily ^{[3] [4]}. The respiration-chamber study used 2.0 mg daily for seven days followed by 1.0 mg for seven days ^[8]. Tesomet combines 0.5 mg tesofensine with 50 mg metoprolol ^[13]. The PET study found that about 0.25 mg produced half the maximum dopamine transporter occupancy ^[10], and the 2008 trial found that 1.0 mg gave only slightly more weight loss than 0.5 mg with more side effects ^[5].

These are reported for information only. There is no approved tesofensine dosage because there is no approved product. Doses in the trials were in fractions of a milligram, an amount that cannot be measured without pharmaceutical manufacturing, and the 2026 metabolism study found marked variability in blood levels between people taking the same dose ^[14]. A tesofensine dosage chart on a vendor site is that vendor’s own invention. Our peptide calculator is built for peptides reconstituted from powder and does not apply to an oral small molecule.

All tesofensine trials used oral tablets or capsules taken once daily ^{[3] [5] [13]}. Online it is sold as capsules marketed as a supplement ^[14] and, by some peptide suppliers, in capsule or liquid form. It is not injected and has never been studied by injection. Tesomet is an oral fixed combination ^[13].

The tesofensine side effects reported in the 2008 obesity trial were dry mouth, nausea, constipation, hard stools, diarrhoea and insomnia. Heart rate rose by 7.4 beats per minute on 0.5 mg, and blood pressure was not significantly raised at 0.25 or 0.5 mg, with the 1.0 mg dose implicitly excluded from that reassurance ^[5]. The 2009 review states that blood pressure rose significantly at the highest dose tested ^[1]. The neurology meta-analysis found dose-dependent heart rate increases from 0.25 mg upward ^[2], and the ADVANS trial reported more neuropsychiatric adverse events at higher doses ^[4].

The 2013 expression of concern and the authors’ letter on under-reporting of adverse effects ^{[6] [7]} mean that the adverse-event profile from the main trial is less complete than the original paper suggested. In the Tesomet trial, one patient had a serious adverse event of worsened pre-existing anxiety that led to discontinuation, and sleep disturbance (50% against 13%), dry mouth (43% against 0%) and headache (36% against 0%) were more common than on placebo; the metoprolol component appears to have blunted the heart rate effect, since no difference in heart rate or blood pressure was seen ^[13]. Rat work has shown that anti-hypertensive treatment preserves appetite suppression while preventing cardiovascular effects, which is the rationale for Tesomet.

Two further points apply to anyone buying it. First, tesofensine is on the World Anti-Doping Agency Prohibited List as an S6 stimulant, prohibited in competition, and it is detectable in urine for weeks ^[14]. Second, a monoamine reuptake inhibitor with a three-week washout that raises heart rate has obvious interaction risks with antidepressants, stimulants and heart medicines, none of which has been studied in the way a licensed drug would require. The abuse-liability study is reassuring on recreational misuse ^[12] but says nothing about these interactions.

Tesofensine vs semaglutide is a comparison between a drug that never completed phase 3 and one with cardiovascular outcome data, so it is a comparison of evidence rather than of numbers. The 10.6% weight loss at 24 weeks in the 2008 trial ^[5] is in the range of early GLP-1 results, but it comes from 203 people in one trial with an acknowledged reporting problem ^{[6] [7]}; semaglutide, tirzepatide and liraglutide have each been tested in thousands of people over 56 to 72 weeks or longer. No trial has compared tesofensine with any GLP-1 drug.

Mechanistically they are unrelated. GLP-1 drugs act on a hormone receptor expressed in the pancreas, gut and brain; tesofensine acts on neurotransmitter transporters. The older centrally acting appetite suppressants that tesofensine most resembles, such as sibutramine, were withdrawn in many countries because of cardiovascular harm, which is why heart rate and blood pressure receive so much attention in the tesofensine literature ^{[2] [5]}. For the drugs that are licensed or in late-stage trials, see peptides for weight loss and our tirzepatide vs semaglutide comparison.

As of September 2026 we could not confirm approval of tesofensine as a medicine by the FDA, the UK MHRA, the European Medicines Agency, the Australian TGA or any other regulator. The 2026 anti-doping study describes it as still under regulatory review ^[14]. It is not a prescription medicine anywhere we could verify, and it is not an ingredient permitted in a dietary supplement in the regulatory sense; the fact that it is sold as one online does not make it lawful.

In the UK, a product containing tesofensine marketed for weight loss would be an unlicensed medicine; see the UK legal status page. In the US, see the US legal status page. The position in Europe, Canada and Australia is covered on those pages, and our legal status overview explains the general rules. Athletes subject to anti-doping rules should note the WADA S6 listing, prohibited in competition only ^[14].

Tesofensine is a stable small molecule, not a peptide, so the cold-chain concerns that apply to peptides such as BPC-157 do not apply in the same way. Tablets and capsules in the trials were stored as ordinary pharmaceuticals. Our guide to how to store peptides is written for reconstituted peptides and is not relevant to an oral capsule. Liquid tesofensine products sold online have no published stability data.

PepFinder does not sell tesofensine. Because it is a small molecule rather than a peptide, the certificate of analysis you should expect differs: purity by HPLC still applies, but there is no molecular weight by mass spectrometry to match against a peptide sequence, and a certificate that presents tesofensine as a peptide is a warning sign in itself. See compare tesofensine prices, how to read a COA and our list of third-party tested suppliers.

We track listings in the UK, the US, Canada, Australia and Europe. No published study has tested the content of tesofensine sold online, although the 2026 metabolism study did use a commercial supplement as its dose source ^[14]. Our guides to third-party peptide testing and spotting a fake supplier cover what to check.