Tesofensine is not a peptide. It’s a small-molecule drug that has never been approved by the FDA. The one published phase 2 trial showed real weight loss, but the journal that printed it later flagged concerns about how the trial was run.
This page covers what that trial found, what the Lancet said about it, and where tesofensine stands now.
What is tesofensine?
Tesofensine is an oral drug that blocks the reuptake of noradrenaline, dopamine and serotonin in the brain. That’s how the 2008 trial authors describe it (Astrup et al., Lancet 2008).
It started as a treatment for Parkinson’s and Alzheimer’s disease. ClinicalTrials.gov lists phase 2 studies of it in both, sponsored by Boehringer Ingelheim and begun in 2003. Weight loss became the focus later.
How much weight did people lose?
The main evidence is one phase 2 trial from Denmark. It enrolled 203 adults with obesity (BMI 30 to 40) at five centers. Everyone got an energy-restricted diet, and they were randomized to placebo or tesofensine 0.25, 0.5 or 1.0 mg once a day for 24 weeks.
The placebo-plus-diet group lost 2.0% of body weight. The tesofensine groups lost more than that:
| Group | Total weight loss at 24 weeks |
|---|---|
| Diet and placebo | 2.0% |
| Tesofensine 0.25 mg | 4.5% |
| Tesofensine 0.5 mg | 9.2% |
| Tesofensine 1.0 mg | 10.6% |
Only 161 of the 203 people (79%) finished the study. The authors wrote that the results needed confirmation in phase III trials.
For comparison, the STEP 1 trial of semaglutide 2.4 mg enrolled 1,961 adults and ran 68 weeks. Weight fell 14.9% on semaglutide versus 2.4% on placebo (Wilding et al., NEJM 2021). The two trials differ in length, size and design, so you can’t read them as a head-to-head result.
What side effects did the trial report?
The most common side effects were dry mouth, nausea, constipation, hard stools, diarrhoea and insomnia. Heart rate rose by 7.4 beats per minute at 0.5 mg, and blood pressure showed no increase over placebo at the 0.25 and 0.5 mg doses (Astrup et al., 2008).
That heart rate rise is the main safety question for a drug that acts on noradrenaline. The trial lasted 24 weeks, so it can’t tell you about long-term heart risk.
Why did the Lancet flag the trial?
In April 2013 the Lancet published an Expression of Concern on the paper. Retraction Watch reported the background:
- The Danish Health and Medicines Authority inspected the trial in November 2011 as part of random checks.
- Concerns were raised about two of the five sites.
- Informed consent was handled by non-medical staff at one site, which Danish rules don’t allow.
- The inspection found that adverse events were not reliably recorded, so the published side-effect profile did not match the actual course of the trial.
The authors replied in a Lancet letter titled Under-reporting of adverse effects of tesofensine. The Expression of Concern is not a retraction. The editors said readers should know about the concerns while they waited on the Danish agency.
Is there a phase 3 trial?
A phase 3 obesity trial of tesofensine ran in Mexico. A 2017 BioSpace report describes a 24-week, placebo-controlled design with up to 372 adults.
Later work moved to Tesomet, a tesofensine and metoprolol combination, in rare conditions. A phase 2 study in Prader-Willi syndrome ran from 2017 to 2019 and is marked completed.
Is tesofensine FDA-approved?
No. The FDA has not approved tesofensine, and it can’t be prescribed in the US. Sellers who offer it online as a “research chemical” are selling an unapproved drug with no quality checks on what’s in the capsule.
This page doesn’t cover where to buy it, doses or cycling schedules. Nothing in the trial data supports self-dosing, and the only published phase 2 weight-loss trial has the flagged safety record described above.
If you want medical weight-loss treatment, talk to a doctor about the FDA-approved options.
Questions
Is tesofensine a peptide?
No. It’s a small-molecule drug that blocks the reuptake of three brain chemicals. It’s often listed with peptides because it’s sold through the same online channels.
How much weight do people lose on tesofensine?
In the 24-week Danish phase 2 trial, 0.5 mg led to 9.2% weight loss, against 2.0% for diet and placebo. The authors said phase III trials were needed to confirm it.
What are the side effects of tesofensine?
The trial reported dry mouth, nausea, constipation, hard stools, diarrhoea and insomnia. Heart rate rose by 7.4 beats per minute at 0.5 mg.
Why did the Lancet issue an Expression of Concern?
After a 2011 inspection by the Danish Health and Medicines Authority, concerns were raised about two of the five trial sites, including consent handling and incomplete recording of adverse events.
Is tesofensine approved by the FDA?
No. The FDA has not approved it, and it can’t be prescribed in the US.