Tesofensine

Dosing from the Literature

Published for fat loss: 0.25, 0.5 and 1 mg once a day by mouth, given with a diet to 203 adults with obesity for 24 weeks in the Phase 2 TIPO-1 trial (Astrup et al., 2008). Not published: the Phase 3 trial in Mexico (0.25 or 0.5 mg a day, 372 people with obesity, 24 weeks), reported only in company announcements (Saniona, December 17, 2018).

The following dosing reflects published clinical trial protocols. This is not medical advice. Tesofensine is investigational; no FDA-approved dose exists.

What It Is

Tesofensine (NS2330) is a centrally acting, orally bioavailable small-molecule drug — not a peptide. Chemically it is a phenyltropane derivative, structurally related to cocaine and to other dopamine-active tropanes, but pharmacologically dissimilar in that its onset is slow and its half-life is extraordinarily long (approximately 220 hours, or roughly 9 days). It functions as a triple monoamine reuptake inhibitor (SMRI), simultaneously blocking the dopamine transporter (DAT), the norepinephrine transporter (NET), and the serotonin transporter (SERT), thereby raising synaptic concentrations of all three neurotransmitters in the central nervous system.

Tesofensine was originally synthesized and developed by the Danish biotechnology company NeuroSearch, in collaboration with Boehringer Ingelheim, beginning in the late 1990s. Its first clinical destinations were neurodegenerative — Phase 2 trials in Alzheimer's disease and Parkinson's disease ran in the early 2000s. Those programs were not successful: tesofensine did not meet the predefined efficacy thresholds for either indication. Boehringer Ingelheim returned the rights to NeuroSearch in 2009. What clinicians did notice consistently in those neurology trials was an unintended, dose-dependent loss of body weight: over 14 weeks, 2.8% on average at 1.0 mg, and 3.7% in obese participants (Astrup et al., 2008; PMID 18356831). That observation pivoted the molecule toward obesity development.

The pivotal anti-obesity result came from the TIPO-1 Phase 2b trial published in The Lancet in 2008 by Astrup and colleagues (PMID 18950853). After 24 weeks, mean weight loss was 4.5%, 9.2%, and 10.6% with tesofensine 0.25 mg, 0.5 mg, and 1.0 mg respectively, all on top of an energy-restricted diet, compared with 2.0% on diet plus placebo. That magnitude — roughly twice that of any anti-obesity agent FDA-approved at the time — generated substantial pharmaceutical and lay-press attention. NeuroSearch subsequently licensed and then sold the program; the program is now owned and run by Saniona, which acquired the rights in 2014. As of April 2026, tesofensine has not received FDA approval for any indication, and the company has voluntarily paused its lead Phase 2b programs in hypothalamic (brain's hormonal control center) obesity and Prader-Willi syndrome citing funding limitations rather than safety or efficacy concerns.

One commonly cited fact about tesofensine — that it is "approved as Tesomet in Mexico" — is overstated. Tesomet is a fixed-dose combination of tesofensine and the beta-1 selective blocker metoprolol, designed to mitigate tesofensine's tachycardic and pressor effects; it is investigational worldwide and has not been granted full marketing authorization by any major regulator. Tesofensine has surfaced increasingly in the optimization community in 2024–2026 because of GLP-1 drug shortages, the rise of body-recomposition discourse, and the migration of attention from off-label semaglutide to non-incretin appetite-suppressant alternatives. None of that use is an approval: tesofensine remains an investigational drug.

Mechanism of Action

Tesofensine blocks the reuptake of dopamine, noradrenaline and serotonin from the synaptic cleft (Appel et al., 2014); in rats and mice it also changes activity in the lateral hypothalamus, a feeding center (Pérez et al., 2024). It is a small molecule, not a peptide: unlike semaglutide, tirzepatide, retatrutide, liraglutide and cagrilintide, it is not an analogue of a gut hormone, and its known targets are the monoamine transporters (Bello & Zahner, 2009).

• Triple monoamine transporter blockade (DAT/NET/SERT) — Tesofensine is a potent inhibitor of all three transporters: in rat brain synaptosomes it blocked noradrenaline, dopamine and serotonin uptake with IC50 values of 1.7, 6.5 and 11 nM (unpublished NeuroSearch data reported by Lehr et al., 2008). Why it failed in Parkinson's is not settled: the trial's authors suggested that blocking dopamine reuptake alone may not help early Parkinson's, that it was not blocked enough, or that other effects offset the benefit (Hauser et al., 2007).
• α1-adrenoceptor pathway dominates appetite suppression in rats — Axel et al. (2010, Neuropsychopharmacology) showed in diet-induced obese rats that tesofensine's hypophagic effect was almost completely reversed by co-administration of prazosin (α1-adrenoceptor antagonist), and partially reversed by SCH23390 (D1 antagonist). The authors concluded that in obese rats it suppresses feeding by indirectly stimulating α1-adrenoceptor and dopamine D1 receptor function.
• Striatal DAT occupancy in humans — Appel et al. (2014, Eur Neuropsychopharmacol; PMID 24239329) used [11C]βCIT-FE PET imaging to measure striatal DAT occupancy after 8–12 days of oral tesofensine at 0.125–1 mg. Mean occupancy rose with dose from 18% to 77%; the estimated maximum was about 80%, half of it reached at about 0.25 mg.
• Lateral hypothalamic GABAergic (related to GABA signaling) neuron silencing — Pérez et al. (2024, PLoS One; PMC11042726, PMID 38656972) found that tesofensine caused more weight loss in obese rats than in lean rats and changed activity in the lateral hypothalamus (LH), a feeding center, differently in the two: in obese rats more LH neurons were inhibited (35% vs 25%) and more were activated (31% vs 11%). In mice, it silenced a subset of LH GABAergic neurons that drive feeding, and silencing those neurons chemogenetically strengthened its effect on food intake.
• Energy expenditure and fat oxidation — Sjödin et al. (2010, Int J Obes; PMID 20479765) gave 32 overweight or moderately obese men two weeks of tesofensine or placebo. Satiety ratings rose and 24-hour fat oxidation rose by 18 g; total 24-hour energy expenditure did not change significantly, though night-time expenditure was 4.6% higher.
• Sympathetic activation drives cardiovascular adverse effects — Bentzen et al. (2013, Obesity) reported in rats that tesofensine raises heart rate and blood pressure by increasing sympathetic activity, and that metoprolol prevented those effects while leaving its suppression of food intake intact. Huynh et al. (2022) cite this rat finding in making the case for Tesomet.
• Long pharmacokinetic tail — In people, tesofensine's half-life is about 234 hours (nearly 10 days). CYP3A4 de-alkylates it to M1, the only metabolite found in human plasma, whose half-life is about 374 hours (about 16 days); in mice, M1 contributed to the drug's activity at the dopamine transporter (Lehr et al., 2008, Br J Pharmacol). At these half-lives, blood levels take weeks to build up and weeks to fall after the last dose.
• What it is not — It is not an incretin or other hormone analogue. Besides blocking monoamine reuptake, it stimulates the cholinergic system indirectly (Lehr et al., 2008).

What the Research Shows

Tesofensine has been studied in three areas: Parkinson's and Alzheimer's disease, where the trials failed (Bello & Zahner, 2009); obesity, with positive Phase 2 results (Astrup et al., 2008) and a Phase 3 in Mexico reported only in company announcements (Saniona, December 17, 2018); and, combined with metoprolol as Tesomet, hypothalamic obesity and Prader-Willi syndrome, where small Phase 2 trials ran (Huynh et al., 2022; NCT03149445) and both Phase 2b trials were withdrawn for lack of funds before anyone was randomized (NCT05147415; NCT05198362).

• TIPO-1 obesity trial (Astrup 2008) — The headline result. 203 obese patients (BMI 30–40) randomized to tesofensine 0.25 mg, 0.5 mg, 1.0 mg, or placebo plus diet for 24 weeks. Mean placebo-corrected weight losses were 2.5%, 7.2%, and 8.6% respectively (4.5%, 9.2%, 10.6% absolute on tesofensine vs 2.0% on placebo). This is approximately twice the magnitude of weight loss reported for sibutramine or rimonabant in comparable trials (PMID 18950853).
• TIPO-4 open-label extension — 140 people who had completed TIPO-1 entered an open-label safety extension (NCT00481104) after a drug-free gap of about 12 weeks, all taking 0.5 or 1.0 mg for 24 weeks; their satiety ratings, which had fallen back to baseline off the drug, rose again when it was restarted (Gilbert et al., 2012).
• Energy metabolism (Sjödin 2010) — In 32 overweight and moderately obese men, two weeks of tesofensine raised satiety and 24-hour fat oxidation (by 18 g); total 24-hour energy expenditure did not change significantly, though night-time expenditure was 4.6% higher (PMID 20479765).
• Tesomet for hypothalamic obesity (Huynh 2022, Eur J Endocrinol) — 21 hypopituitary adults with acquired hypothalamic obesity (NCT03845075) randomized 2:1 to Tesomet (0.5 mg tesofensine + 50 mg metoprolol) vs placebo for 24 weeks, then 24-week open-label extension. Mean change in body weight was −7.4 kg with Tesomet vs −0.4 kg on placebo (difference −6.9 kg; P = 0.02). No significant difference in heart rate or blood pressure between groups; the authors suggest metoprolol can offset tesofensine's rise in heart rate and blood pressure (PMID 35294397).
• Tesomet for Prader-Willi syndrome (Phase 2a, NCT03149445) — Nine adults took 0.5 mg tesofensine + 50 mg metoprolol (6) or placebo (3) once daily for 91 days; in the registry's posted results, scores for hyperphagia, the defining symptom of PWS, fell more on Tesomet (−8.5 vs −4.0 points, p = 0.006), but the weight difference (−4.1% vs −0.4%) was not significant. Because the drug's half-life was longer than expected in PWS, nine adolescents then took a quarter of the tesofensine dose, 0.125 mg with 25 mg metoprolol (Saniona, January 7, 2019); their weight and hyperphagia did not differ from placebo (NCT03149445). Open-label extensions at 0.125 mg and then 0.25 mg followed, with too few patients for formal statistics (Saniona, September 18, 2019). FDA granted Tesomet orphan drug designation for PWS in 2021 (Saniona, first-quarter 2021 report) and confirmed the 505(b)(2) regulatory pathway is open.
• Phase 2b PWS and hypothalamic obesity trials initiated then withdrawn — Saniona opened Phase 2b trials in both indications in late 2021 (registry start dates November and December 2021): a 16-week double-blind PWS trial and a 36-week hypothalamic obesity trial, each with an open-label extension (NCT05198362; NCT05147415). It paused both in March 2022 for funding reasons, not safety or efficacy (Saniona, March 29, 2022), and ClinicalTrials.gov lists both as withdrawn in December 2022, with no one randomized.
• Failed neurodegenerative arc (Hauser 2007 early PD; Rascol 2008 ADVANS advanced PD; PMID 18474731) — Two well-conducted Phase 2 randomized double-blind placebo-controlled trials in Parkinson's disease. Hauser 2007 (Movement Disorders) tested tesofensine 0.25/0.5/1.0 mg as monotherapy in 261 early-PD patients; the 1.0 mg arm produced a transient UPDRS improvement at week 6 that did not sustain. Rascol 2008 ADVANS tested 0.125/0.25/0.5/1.0 mg as adjunct to levodopa in advanced PD with motor fluctuations; small mean improvements (e.g., −4.7 UPDRS points and −7.1% off time at certain doses) were observed but were not clinically transformative. Boehringer Ingelheim concluded these and one Alzheimer's trial did not meet predefined Phase 3 progression criteria and returned rights to NeuroSearch.
• Cognitive and Alzheimer's signal — minimal — A pharmacokinetic-pharmacodynamic modeling paper (Lehr et al., 2010, AAPS J) notes a Phase 2a Alzheimer's signal that did not reproduce in Phase 2b. Astrup et al. (Obesity 2008; PMID 18356831) summarized weight loss in PD/AD trial cohorts as the consistent off-target finding that ultimately redirected development.
• Preclinical DIO rat models — Hansen et al. (2010, Eur J Pharmacol) compared tesofensine head-to-head with sibutramine and rimonabant in diet-induced obese rats. Tesofensine produced more sustained weight loss and superior glycemic control improvement than either comparator at allometrically scaled doses. The cafeteria-fed DIO female rat model used in Heal/Smith comparison studies has approximately 95% predictive correlation with human anti-obesity drug efficacy, lending unusually high translational confidence to these preclinical results.
• Abuse potential — low (Schoedel 2010, Clin Pharmacol Ther) — Single-dose, randomized, double-blind, crossover study in 52 recreational stimulant users compared tesofensine against placebo, D-amphetamine 30 mg (positive control), bupropion, and atomoxetine. Tesofensine's subjective effects were not significantly different from placebo and were lower than D-amphetamine's on all primary and most secondary measures. Conclusion: its abuse potential is no greater than that of bupropion or atomoxetine, and it is unlikely to be recreationally abused (PMID 20520602).

Human Data

Tesofensine has accumulated more high-quality human data than most compounds in this database — it is a small-molecule pharmaceutical asset that has run multiple completed Phase 2 trials with peer-reviewed publications. The contrast with peptides like BPC-157 (3 small pilots) is significant. What it lacks is a published Phase 3: the one Phase 3 trial, in Mexico, has been reported only in company announcements (Saniona, December 17, 2018).

• NCT00394667 — Phase 2 obesity trial (TIPO-1); its open-label extension, TIPO-4, is registered separately (NCT00481104). Foundation of the entire obesity development arc. Published as Astrup 2008 Lancet (PMID 18950853).
• NCT03845075 — Phase 2 randomized placebo-controlled trial of Tesomet in 21 adults with acquired hypothalamic obesity. Published as Huynh 2022 Eur J Endocrinol (PMID 35294397). Mean −7.4 kg vs −0.4 kg on placebo at 24 weeks.
• NCT03149445 — Phase 2a exploratory Tesomet trial in adults and adolescents with Prader-Willi syndrome. In the registry's posted results, adults on Tesomet had a larger fall in hyperphagia score than on placebo but no significant difference in weight; adolescents on a quarter of the dose showed neither. Company press releases (2019) summarize the results.
• Phase 2b PWS trial (withdrawn) — Listed as starting December 2021: 16-week double-blind + 36-week open-label extension. Paused in March 2022 for funding (Saniona, March 29, 2022) and withdrawn with no one randomized (NCT05198362).
• Phase 2b hypothalamic obesity trial (withdrawn) — Listed as starting November 2021: 36-week double-blind + 36-week open-label extension. Paused in March 2022 for funding and withdrawn with no one randomized (NCT05147415).
• Parkinson's Phase 2 (Hauser 2007 / Rascol 2008) — 261 early-PD patients (Hauser) and 254 advanced-PD patients (Rascol ADVANS, PMID 18474731; NCT00148512). Negative or marginal efficacy. In a pooled analysis of four Parkinson's and Alzheimer's trials, tesofensine raised heart rate with no effect on blood pressure and caused the weight loss that drove the obesity pivot (Astrup et al., 2008; PMID 18356831).
• Alzheimer's Phase 2 — Two small 4-week Phase 2a trials in 62 people with mild Alzheimer's showed a cognitive improvement; a 14-week Phase 2b trial in 430 people with mild-to-moderate Alzheimer's did not meet the efficacy criteria to proceed to Phase 3. A modeling paper (Lehr 2010, AAPS J) showed the Phase 2a data predicted that negative Phase 2b result.
• Healthy volunteer abuse-liability study (Schoedel 2010, PMID 20520602) — 52 recreational stimulant users; tesofensine indistinguishable from placebo on subjective drug-effect measures. The drug is therefore unlikely to be scheduled by DEA in any restrictive category if it ever achieves U.S. approval.
• PET DAT occupancy (Appel 2014, PMID 24239329) — Quantified striatal dopamine transporter occupancy across the clinical dose range: after 8–12 days at 0.125–1 mg, mean occupancy rose with dose from 18% to 77%, with an estimated maximum of about 80%.

What the existing dataset does not address: long-term cardiovascular safety beyond 24 weeks, MACE outcomes, sustainability of weight loss past 1 year, head-to-head against semaglutide/tirzepatide, behavior in adolescents outside PWS, drug-drug interactions with common chronic medications, and outcomes in patients with established cardiovascular disease. None of these have been studied at the scale modern obesity drug regulation requires.

Reconstitution & Storage

Tesofensine is a small-molecule oral drug. Unlike peptides in this database, it is not lyophilized and does not require reconstitution. In the trials it was given as once-daily tablets (Rascol et al., 2008; NCT03845075).

No label exists, so no official storage conditions or shelf life have been set.

• No reconstitution required — Tesofensine is administered orally as the supplied solid dosage form. It is not reconstituted or injected.
• Long terminal half-life — About 234 hours (nearly 10 days) for tesofensine and about 374 hours (16 days) for its active metabolite M1 (Lehr et al., 2008).

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Side Effects & Risks

The side effects below come from TIPO-1, the Parkinson's trials and the Tesomet trials:

• Cardiovascular — the primary concern — At 0.5 mg, heart rate rose 7.4 beats per minute more than on placebo in TIPO-1, with no significant change in blood pressure (Astrup et al., 2008). Heart rate rose with dose, and blood pressure rose significantly at the highest dose tested (Bello & Zahner, 2009). Letters to The Lancet (Tsai, PMID 19249625; Sommet et al., PMID 19249626) emphasized that exclusion of psychiatric and cardiovascular-risk patients from TIPO-1 may underestimate real-world cardiovascular adverse events. In 2013 The Lancet published an expression of concern about the trial report (PMID 23561987). In the Tesomet trial, heart rate and blood pressure did not differ from placebo (Huynh et al., 2022).
• Common side effects — In TIPO-1 the most common were dry mouth, nausea, constipation, hard stools, diarrhea, and insomnia (Astrup et al., 2008); in the Tesomet trial, sleep disturbances (50% vs 13% on placebo), dry mouth (43% vs 0%), and headache (36% vs 0%) (Huynh et al., 2022). In advanced Parkinson's, gastrointestinal and neuropsychiatric adverse events were more frequent at higher doses (Rascol et al., 2008).
• Psychiatric — mood changes and anxiety — In TIPO-1, 1.0 mg daily for 24 weeks significantly increased confusion, vigour and activity, anger, and hostility on the Profile of Mood States (POMS) vs placebo, with no significant change in depression, tension, or fatigue (Astrup et al., 2008, as reported by Huynh et al., 2022). A 2009 evaluation of the trial noted that it may increase psychiatric disorders (Doggrell, 2009). In the Tesomet trial, one patient stopped treatment because of severe anxiety and paranoia, a worsening of pre-existing anxiety (Huynh et al., 2022). Real-world prevalence in unselected populations is unknown.
• Abuse potential — low in recreational stimulant users — In Schoedel 2010 (PMID 20520602), single doses of tesofensine produced subjective drug effects no different from placebo in 52 recreational stimulant users, lower than D-amphetamine 30 mg.
• Long half-life — The half-life in people is nearly 10 days (about 234 hours), and about 16 days for the active metabolite M1 (Lehr et al., 2008), so blood levels take weeks to build up after a dose change and weeks to fall after the last dose.
• Drug-drug interactions — CYP3A4 — Tesofensine is metabolized mainly by CYP3A4 (Lehr et al., 2010), so in theory strong CYP3A4 inhibitors (such as azole antifungals) could raise its levels and inducers (such as rifampicin) lower them. Because it also blocks serotonin reuptake (Lehr et al., 2008), combining it with other serotonergic drugs (SSRIs, SNRIs, MAOIs, tramadol) carries a theoretical risk of serotonin syndrome, and other stimulants would in theory add to its rise in heart rate.
• Contraindications — not set — No FDA label exists, so no contraindications have been set. The Tesomet trial excluded people with arrhythmias, a heart attack or stroke in the past 5 years, blood pressure of 160/90 mmHg or more, a resting heart rate of 90 or more or below 50, or a psychiatric diagnosis (Huynh et al., 2022).
• WADA status — Tesofensine is named on the 2026 Prohibited List under S6 (stimulants), prohibited in competition (Krug et al., 2026).
• Sourcing risk — Tesofensine bought online is sold as a research chemical, outside any drug regulator's checks on purity or identity.

Quick Compare — Tesofensine vs Semaglutide vs Tirzepatide vs Phentermine

The table compares tesofensine with the incretin drugs semaglutide and tirzepatide and with phentermine. These are mechanistically distinct, dose differently, have very different evidence bases, and carry different side-effect profiles.

→ See Semaglutide profile  •  → See Tirzepatide profile  •  → See Cagrilintide profile

Bloodwork & Monitoring

No label or guideline sets monitoring for tesofensine. TIPO-1 tracked heart rate and blood pressure and measured body composition and quality of life (Astrup et al., 2008). The Tesomet trial tracked adverse events, blood tests and vital signs; ECG, 24-hour blood pressure and 48-hour Holter recordings at screening, week 12 and week 24; a depression questionnaire (PHQ-9); and body composition by DXA at the start and at week 24 (Huynh et al., 2022).

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References

1. Astrup A, Madsbad S, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Nov 29;372(9653):1906-1913. doi: 10.1016/S0140-6736(08)61525-1. PMID: 18950853. (TIPO-1 — the foundational Phase 2b obesity trial.)
2. Doggrell SA. Tesofensine — a novel potent weight loss medicine. Evaluation of: Astrup A, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss... Lancet 2008;372:1906-13. Expert Opin Investig Drugs. 2009 Jul;18(7):1043-6. PMID: 19548858.
3. Astrup A, Meier DH, Mikkelsen BO, Villumsen JS, Larsen TM. Weight loss produced by tesofensine in patients with Parkinson's or Alzheimer's disease. Obesity (Silver Spring). 2008 Jun;16(6):1363-9. PMID: 18356831.
4. Hauser RA, Salin L, Juhel N, Konyago VL, et al. Randomized trial of the triple monoamine reuptake inhibitor NS 2330 (tesofensine) in early Parkinson's disease. Mov Disord. 2007 Feb 15;22(3):359-365. doi: 10.1002/mds.21258.
5. Rascol O, Poewe W, Lees A, Aristin M, Salin L, Juhel N, Waldhauser L, Schindler T; ADVANS Study Group. Tesofensine (NS 2330), a monoamine reuptake inhibitor, in patients with advanced Parkinson disease and motor fluctuations: the ADVANS Study. Arch Neurol. 2008 May;65(5):577-83. PMID: 18474731.
6. Bello NT, Zahner MR. Tesofensine, a monoamine reuptake inhibitor for the treatment of obesity. Curr Opin Investig Drugs. 2009 Oct;10(10):1105-16. PMID: 19777399.
7. Sjödin A, Gasteyger C, Nielsen AL, Raben A, Mikkelsen JD, Jensen JK, Meier D, Astrup A. 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 Nov;34(11):1634-43. doi: 10.1038/ijo.2010.87. PMID: 20479765.
8. Schoedel KA, Meier D, Chakraborty B, Manniche PM, Sellers EM. Subjective and objective effects of the novel triple reuptake inhibitor tesofensine in recreational stimulant users. Clin Pharmacol Ther. 2010 Jul;88(1):69-78. doi: 10.1038/clpt.2010.67. PMID: 20520602. (Abuse-liability study — supports low scheduling risk.)
9. Appel L, Bergström M, Buus Lassen J, Långström B. Tesofensine, a novel triple monoamine re-uptake inhibitor with anti-obesity effects: dopamine transporter occupancy as measured by PET. Eur Neuropsychopharmacol. 2014 Feb;24(2):251-61. doi: 10.1016/j.euroneuro.2013.10.007. PMID: 24239329.
10. Axel AM, Mikkelsen JD, Hansen HH. Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of α1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat. Neuropsychopharmacology. 2010 May;35(7):1464-76. doi: 10.1038/npp.2010.16. (PMC3055463.)
11. Hansen HH, Hansen G, Tang-Christensen M, Larsen PJ, Axel AM, Raben A, Mikkelsen JD. The novel triple monoamine reuptake inhibitor tesofensine induces sustained weight loss and improves glycemic control in the diet-induced obese rat: comparison to sibutramine and rimonabant. Eur J Pharmacol. 2010 Jun 25;636(1-3):88-95. doi: 10.1016/j.ejphar.2010.03.026.
12. Bentzen BH, Grunnet M, Hyveled-Nielsen L, Sundgreen C, Lassen JB, Hansen HH. Anti-hypertensive treatment preserves appetite suppression while preventing cardiovascular adverse effects of tesofensine in rats. Obesity (Silver Spring). 2013 May;21(5):985-92. doi: 10.1002/oby.20122. (Pharmacological rationale for Tesomet.)
13. Lehr T, Staab A, Tillmann C, Nielsen EO, Trommeshauser D, Schaefer HG, Kloft C. Contribution of the active metabolite M1 to the pharmacological activity of tesofensine in vivo: a pharmacokinetic-pharmacodynamic modelling approach. Br J Pharmacol. 2008 Jan;153(1):164-74. doi: 10.1038/sj.bjp.0707539.
14. Lehr T, Staab A, Trommeshauser D, Schaefer HG, Kloft C. Quantitative pharmacology approach in Alzheimer's disease: efficacy modeling of early clinical data to predict clinical outcome of tesofensine. AAPS J. 2010 Sep;12(3):117-29. doi: 10.1208/s12248-009-9164-6.
15. Huynh KD, Klose M, Krogsgaard K, Drejer J, Byberg S, Madsbad S, Magkos F, Aharaz A, Edsberg B, Tfelt-Hansen J, Astrup AV, Feldt-Rasmussen U. Randomized controlled trial of Tesomet for weight loss in hypothalamic obesity. Eur J Endocrinol. 2022 Apr 28;186(6):687-700. doi: 10.1530/EJE-21-0972. PMID: 35294397. (NCT03845075.)
16. Pérez CI, Luis-Islas J, Lopez A, Diaz-Sosa X, Pérez-Freitez K, Ruiz-Pérez L, Hattar S, Zarco N, Brito-Aquino N, Jaime-Lara R, Almanza A, Calvo-Ochoa E, Tellez LA, Gutierrez R. Tesofensine, a novel antiobesity drug, silences GABAergic hypothalamic neurons. PLoS One. 2024 Apr 24;19(4):e0300544. doi: 10.1371/journal.pone.0300544. PMID: 38656972. (PMC11042726 — circuit-level mechanism in lateral hypothalamus.)
17. Tsai AG. Tesofensine and weight loss. Lancet. 2009 Feb 28;373(9665):719; author reply 720. doi: 10.1016/S0140-6736(09)60432-3. PMID: 19249625.
18. 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 Apr 6;381(9873):1167. doi: 10.1016/S0140-6736(13)60778-3. PMID: 23561987.
19. Halford JC, Boyland EJ, Blundell JE, Kirkham TC, Harrold JA. Pharmacological management of appetite expression in obesity. Nat Rev Endocrinol. 2010 May;6(5):255-69. doi: 10.1038/nrendo.2010.19. PMID: 20234354.
20. Saniona AB. Tesomet — Pipeline. saniona.com/pipeline/tesomet. Accessed April 2026. (Phase 2b PWS and hypothalamic obesity trials voluntarily paused due to funding limitations; not safety/efficacy.)
21. ClinicalTrials.gov. NCT03845075 — Randomized Controlled Trial of Tesomet in Adults With Hypothalamic Obesity. NCT03149445 — Phase 2a Tesomet in Prader-Willi Syndrome. NCT00394667 — Effect of Tesofensine on Weight Reduction in Patients With Obesity. clinicaltrials.gov.
22. FDA. Bulk Drug Substances Nominated for Use in Compounding — 503A and 503B Categories. FDA.gov. Updated 2025–2026. (Tesofensine not eligible for U.S. compounding under current bulk-substance lists.)
23. Saniona AB. Saniona's tesofensine meets primary and secondary endpoints in Phase 3 obesity registration trial. Press release, December 17, 2018. globenewswire.com. Read October 3, 2026. (Phase 3 run by partner Medix in Mexico: 372 people with obesity, tesofensine 0.25 or 0.50 mg or placebo once daily for 24 weeks.)
24. Gilbert JA, Gasteyger C, Raben A, Meier DH, Astrup A, Sjödin A. The effect of tesofensine on appetite sensations. Obesity (Silver Spring). 2012 Mar;20(3):553-61. doi: 10.1038/oby.2011.197. PMID: 21720440. (Appetite in TIPO-1 and its open-label extension, TIPO-4.)
25. ClinicalTrials.gov. NCT00481104 — Evaluation of Long Term Safety of Tesofensine in Patients With Obesity (TIPO-4: open-label extension for 140 patients who completed TIPO-1; May 2007 – November 2008). clinicaltrials.gov. Read October 3, 2026.
26. Krug O, Thomas A, Thevis M. Investigations Into the Metabolism and Elimination of Tesofensine in Human Urine. Drug Test Anal. 2026;18(9):1163-1173. PMID: 42320973. DOI: 10.1002/dta.70104.

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