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Tsf4.0
Tesofensine Research
Mostly mechanism / observationalLimited safety
7 peer-reviewed studies
What the evidence says
Mostly mechanism / observational
Most Tesofensine studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from medium-quality meta-analyses and randomised trials published 2008–2024 with a typical study size of 203 participants.
Based on 7 studies · 1 meta-analysis · 3 RCTs · 1,224 total participants
Confidence
Moderate
By outcome
Weight loss & appetite
Mostly mechanism / observational7 studies
Heart rate & cardiovascular (trade-off)
Mostly mechanism / observational3 studies
Mood & psychiatric (trade-off)
Mostly mechanism / observational3 studies
Safety profile
Mostly mechanism / observational3 studies
Steady research
2 studies in the last 5 years · Latest meta-analysis: 2008
200820162024
1RCTn=203 · medium study2008
Tesofensine 0.25 mg, 0.5 mg, and 1.0 mg and diet induced a mean weight loss of 4.5%, 9.2%, and 10.6%, respectively, greater than diet and placebo (p<0.0001).
TIPO-1 phase-2 double-blind RCT (n=203) of once-daily oral tesofensine 0.25/0.5/1.0 mg vs placebo plus an energy-restricted diet over 24 weeks
Mean total weight loss ~4.5% (0.25 mg), ~9.2% (0.5 mg) and ~10.6% (1.0 mg) vs ~2% on diet+placebo (≈2.5/7.2/8.6% placebo-subtracted) — about twice the weight loss of the obesity drugs approved at the time
Most common adverse events were dry mouth, nausea, constipation, diarrhoea and insomnia; heart rate rose 7.4 bpm in the 0.5 mg group (p=0.0001)
Tesofensine produced a placebo-subtracted weight loss of approximately 4% for >14 weeks without any diet and lifestyle therapy, which is similar to that of sibutramine, but with no effect on blood pressure.
Meta-analysis pooling four randomized, double-blind trials of tesofensine in Parkinson's or Alzheimer's disease (TE n=740, placebo n=228) over 14 weeks, with weight as a secondary signal
Dose-dependent weight loss even WITHOUT a weight-loss program: -0.5% to -2.8% across 0.125-1.0 mg vs +0.5% placebo (p=0.015 for dose effect); larger in the obese subgroup
Heart rate rose dose-dependently (+2.1 to +6.8 bpm; p<0.001 from 0.25 mg) with no effect on blood pressure
Tesofensine has a pronounced effect on appetite sensations and a slight effect on energy expenditure at night — both effects can contribute to the strong weight-reducing effect.
Sjödin A, Gasteyger C, Nielsen AL, Raben A, Mikkelsen JD, Jensen JK, Meier D, Astrup A. · Int J Obes (Lond) (2010)
Randomized controlled respiration-chamber crossover trial (n=32 overweight/obese men) measuring 24-h energy expenditure, fat oxidation and appetite
Mechanistic anchor: tesofensine raised satiety and fullness and lowered prospective food intake — appetite suppression is the dominant driver of weight loss in humans
Modest metabolic contribution: higher night-time energy expenditure (+4.6%) and increased 24-h fat oxidation (+18 g)
Compared to placebo, Tesomet resulted in additional mean weight change of -6.3%... increased the number of patients achieving ≥5% weight loss... [and] did not affect heart rate or blood pressure.
Huynh K, Klose M, Krogsgaard K, Drejer J, Byberg S, Madsbad S, Magkos F, Aharaz A, Edsberg B, Tfelt-Hansen J, Astrup AV, Feldt-Rasmussen U. · Eur J Endocrinol (2022)
Phase-2 double-blind RCT (n=21) of Tesomet (0.5 mg tesofensine + 50 mg metoprolol) vs placebo over 24 weeks in hard-to-treat hypothalamic obesity
Significant placebo-subtracted weight loss (-6.3%) and more patients reaching ≥5% loss (8/13 vs 1/8); the added beta-blocker kept heart rate and blood pressure unchanged
One Tesomet-related serious adverse event — exacerbated pre-existing anxiety leading to discontinuation; sleep disturbance, dry mouth and headache were more frequent than placebo
Tesofensine inhibited a subset of LH GABAergic neurons, reducing their ability to promote feeding behavior... and blocked the body weight rebound that often occurs after weight loss.
Perez CI, Luis-Islas J, Lopez A, Diaz X, Molina O, Arroyo B, Moreno MG, Lievana EG, Fonseca E, Castañeda-Hernández G, Gutierrez R. · PLoS One (2024)
Mechanistic rodent study (mice and rats) using electrophysiology, optogenetics and chemogenetics in the lateral hypothalamus
Tesofensine silences a feeding-promoting subset of lateral-hypothalamic GABAergic neurons and induces greater weight loss in obese than lean rats
Prolonged 5-HTP-induced weight loss and blocked the post-weight-loss body-weight rebound; few head-weaving stereotypies vs phentermine at therapeutic doses
The monoaminergic re-uptake inhibitor tesofensine has also been shown to produce impressive weight loss in smaller-scale clinical studies... behavioural specificity and psychological side effects remain an issue.
Review of centrally-acting serotonergic and monoaminergic appetite suppressants for obesity, placing tesofensine alongside lorcaserin and the withdrawn fenfluramine/sibutramine class
Notes tesofensine produces 'impressive' weight loss but that the data are smaller-scale, and it strengthens satiety
Flags that behavioural specificity and psychological side effects 'remain an issue' — the explicit psychiatric caveat