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Investigational oral drug · obesity evidence under formal concern
Tesofensine
Tesofensine’s main paper has a formal Lancet warning. Read the studied doses and weight results. These do not set an approved dose.
- The Lancet placed a formal expression of concern on the main paper.
- The reported weight figures must be read with that warning.
- Tesomet is a separate two-drug treatment studied in a different group.
Tesofensine is a small-molecule oral drug. It blocks reuptake of norepinephrine, dopamine and serotonin. It is not a peptide.
It is not a GLP-1 receptor agonist.
The main Phase 2 obesity trial assigned 203 adults to study groups. They took 0.25, 0.5, or 1.0 mg daily, or placebo, for 24 weeks. All also followed an energy-restricted diet.
The paper gave weight-loss differences of 4.5, 9.2, and 10.6 percentage points at those doses. These were differences from placebo, not total weight loss. Only 161 people finished. The Lancet later placed a formal expression of concern on the article. Its figures must be read with that warning.
They do not establish an approved dose or personal schedule.
What matters first
- The main paper has a formal warning: Its expression of concern must be read with the findings. The article is not an ordinary, unchallenged source of benefit evidence.
- Assigned and finished are different counts: The paper gives 203 randomly assigned people. Only 161 finished. Neither count can replace the other.
- The figures are differences from placebo: The 4.5, 9.2, and 10.6 values are percentage points greater than diet plus placebo. They are not total weight loss in each drug group.
- Tesomet has two drugs: Its result is for 0.5 mg tesofensine plus 50 mg metoprolol. It is not a result for tesofensine on its own.
- Study amounts are not advice: Each amount belongs to its tested group and duration. It also depends on the comparison treatment and other care given in that study.
- Approval checks have limits: No product was found in the current US databases checked. A favorable Mexican committee opinion is not binding. Current Mexican registration could not be verified.
TIPO-1: the Phase 2 obesity study under expression of concern
The TIPO-1 paper describes a trial at five Danish obesity centers. It used random group assignment, double blinding and a placebo control. Adults had BMI 30–40 kg/m².
After a two-week run-in, they followed an energy-restricted diet. They took one oral study treatment each day for 24 weeks.
| Randomized arm | Assigned n | Result reported at 24 weeks |
|---|---|---|
| Tesofensine 0.25 mg once daily | 52 | 4.5 percentage points greater mean weight loss than diet plus placebo |
| Tesofensine 0.5 mg once daily | 50 | 9.2 percentage points greater mean weight loss than diet plus placebo |
| Tesofensine 1.0 mg once daily | 49 | 10.6 percentage points greater mean weight loss than diet plus placebo |
| Placebo once daily | 52 | 2.0% mean weight loss with the energy-restricted diet |
The four groups total 203 randomly assigned people. The paper says 161, or 79%, finished. Its main analysis was modified intention to treat.
This meant assigned people with a measure after at least one dose. The NCT00394667 registry gives estimated enrollment of 200. It has no posted results.
That estimate cannot replace the paper’s exact group or completion counts.
The paper lists dry mouth, nausea, constipation, hard stools, diarrhea and insomnia as common adverse events linked to the drug. At 0.5 mg, heart rate was 7.4 beats per minute higher after 24 weeks. At 0.25 and 0.5 mg, systolic and diastolic blood-pressure rises were not significant versus placebo.
These are selected abstract findings. They are not a complete safety profile.
Why the expression of concern must stay beside the numbers
PubMed links TIPO-1 to the Lancet’s formal expression of concern. It also links the authors’ reply, “Under-reporting of adverse effects of tesofensine”. The later Tesomet paper describes a Danish regulator’s audit.
It raised concerns that headache, migraine, stress and depression were under-reported. That paper says the authors acknowledged under-reporting across centers. It also says they lacked enough data to judge cause.
The formal concern does not prove that the three benefit figures are false. It also does not confirm them independently. The warning belongs beside the results, including at the start.
The reported values remain as published. TIPO-1 cannot support an unchallenged benefit headline.
Other tesofensine use on its own studies
These studies asked narrower questions in different groups. They do not validate TIPO-1.
| Evidence | Population and studied oral schedule | Result and limit |
|---|---|---|
| Pooled neurodegenerative-disease analysis | Four randomized trials included 740 tesofensine and 228 placebo people with Parkinson’s or Alzheimer’s disease. Tesofensine was given once daily at 0.125, 0.25, 0.5, or 1.0 mg for 14 weeks without a weight-loss program. | Mean weight change in the full cohort was +0.5% with placebo and −0.5%, −0.9%, −1.8%, and −2.8% across the four doses. Heart-rate changes were −0.4, +2.1, +4.2, +6.0, and +6.8 beats/minute in the same order. This was a pooled secondary analysis in neurologic disease, not an obesity-treatment trial or proof of functional benefit. |
| Short energy-balance study | Thirty-two healthy men with overweight or moderate obesity received 2.0 mg daily for seven days followed by 1.0 mg daily for seven days, or placebo, while maintaining usual food intake and activity. | Tesofensine produced 1.8 kg more weight loss than placebo and higher satiety ratings. Total 24-hour energy expenditure did not differ significantly; small night-time expenditure and fat-oxidation changes were reported. This two-week mechanistic step-down protocol is not a longer treatment schedule. |
Tesomet is combination evidence
The Tesomet paper and NCT03845075 describe a 24-week trial. Adults with hypothalamic obesity were randomly assigned to groups. The active treatment was 0.5 mg tesofensine plus 50 mg metoprolol once daily.
The plan included a 300 kcal/day dietary deficit and monthly lifestyle counseling. Safety was the main endpoint. Weight measures were secondary.
The counts answer different questions:
| Count | What it represents |
|---|---|
| 21 | Unique adults randomized; this is the registry’s actual enrollment and the paper’s unique-participant count |
| 22 | Randomization records and safety exposures: one participant was randomized in error, received one active dose, then was re-screened 78 days later and randomized to placebo |
| 14 active and 8 placebo | Safety-analysis records; the twice-randomized participant appears in both groups |
| 13 active and 8 placebo | Modified intention-to-treat benefit populations; the participant appears only in the placebo group |
| 18 | People who completed the 24-week controlled period |
At week 24, the least-squares mean weight changes were −6.6% with Tesomet and −0.3% with placebo. The placebo-adjusted difference was −6.3 percentage points (95% CI −11.3 to −1.3). The modified intention-to-treat groups had 13 active and 8 placebo records.
Missing values used the last observation carried forward. These are analysis counts, not counts seen at week 24. At least 5% weight loss occurred in 8/13 active and 1/8 placebo benefit records.
One person had a treatment-related serious event: worsening pre-existing anxiety. It led to stopping study treatment.
The result has several limits. The group was small, and safety was the main question. One person was randomly assigned again.
Treatment had two drugs plus a dietary plan. The paper also disclosed sponsor relationships. The −6.3 percentage-point estimate belongs to Tesomet, not tesofensine alone.
Safety counts of 14 and 8 count exposures. They are not 22 unique people and cannot be pooled as a people count.
Current study and regulatory status
The current trial search returns 13 records. Of these, 11 are completed and two withdrawn. None is recruiting, active or Phase 3.
The two withdrawn Tesomet trials enrolled no people. Both the hypothalamic-obesity trial and Prader-Willi trial cite financing as the reason. Their planned groups are not exposures or results.
FDA describes Drugs@FDA as its approved-product database. Its September 4, 2026 page and 12-table archive were checked. Searches used tesofensine, tesofensina, NS2330, and NS 2330.
None matched. The exact openFDA ingredient query returned HTTP 404 “No matches found.” The exact DailyMed search returned zero labels. No product was found in these current US databases.
That does not establish worldwide approval status. It supplies no approval, approved use, label or recommended dose.
Mexico’s official 2023 ledger gives a favorable committee opinion on February 23, 2023. COFEPRIS calls this committee a consultation and opinion body. Its opinions are nonbinding and come before a registration decision.
An April 2026 announcement points to a live viewer for current registration. The viewer gave no HTTP response before this session timed out. The opinion does not prove current Mexican registration.
That remains unresolved here.
Reader questions
What doses of tesofensine were studied for obesity?
TIPO-1 assigned oral doses of 0.25, 0.5, or 1.0 mg once daily for 24 weeks. People also followed an energy-restricted diet. These are research doses from a paper under formal expression of concern.
They are not an approved dose or personal dose-escalation plan.
Did the study show 4.5%, 9.2%, and 10.6% total weight loss?
No. The abstract reports 4.5, 9.2, and 10.6 percentage points greater weight loss than diet plus placebo at those doses. The diet-plus-placebo group lost 2.0% on average.
These values must not be added to create new group totals. The article has a formal Lancet expression of concern about adverse-event reporting. Its figures are not unchallenged or independently confirmed evidence of benefit.
How many people were in TIPO-1?
The paper gives 203 randomly assigned people and 161 who finished. The registry’s estimate of 200 is a different field. It cannot replace either published count.
Is Tesomet another name for tesofensine?
Tesomet has two drugs: 0.5 mg tesofensine plus 50 mg metoprolol once daily. Its result in hypothalamic obesity cannot be assigned to tesofensine alone.
Is tesofensine approved in the United States or Mexico?
No product was found in the current US databases checked. Mexico’s reviewed record is a favorable but nonbinding committee opinion. The live viewer gave no response.
Current registration therefore remains unresolved. Neither check supplies an approved dose.
Can these study amounts be used as a personal schedule?
No. The amounts describe controlled research in selected groups. They do not establish a consumer schedule, clinical recommendation or wellness use.