Tesofensine

updated September 11, 2026

What is Tesofensine?

Tesofensine is the parent active moiety. A citrate salt changes the mass relationship, Tesomet adds metoprolol, and M1 is an active metabolite. Studies of the combination or metabolite cannot be read as studies of tesofensine alone.

Tesofensine reduced weight in the 24-week TIPO-1 trial, but it also raised heart rate. The paper carries an Expression of Concern about adverse-event reporting and trial conduct. The cited U.S. records list no approval, and the cited Mexican records document application activity rather than final authorization.

Monoamine reuptake inhibitor

Oral small molecule, not a peptide
Inhibits monoamine reuptake
Tesomet combines tesofensine with metoprolol

What did the TIPO-1 phase 2 trial report?

After 24 weeks with an energy-restricted diet, mean weight loss was 2.0% with placebo and diet, 4.5% with 0.25 mg, 9.2% with 0.5 mg, and 10.6% with 1.0 mg tesofensine. The 0.5 mg arm increased heart rate by 7.4 beats per minute versus placebo.

Common reported effects included dry mouth, nausea, constipation, hard stools, diarrhea, and insomnia. Only 161 of 203 randomized participants completed the study.

TIPO-1 · efficacy and heart rate

Randomized trial under Expression of Concern

Astrup et al., The Lancet, 2008

In 203 adults, tesofensine produced dose-related 24-week weight loss; the 0.5 mg arm increased heart rate by 7.4 beats per minute.

Participants / model: Adults with BMI 30 to 40
Treatment: Tesofensine 0.25, 0.5, or 1.0 mg daily or placebo, all with diet
Follow-up: 24 weeks
Study design: Randomized, double-blind, placebo-controlled phase 2 trial

The paper carries a 2013 Expression of Concern that materially limits confidence.

Read the original source

What does the Lancet Expression of Concern change?

The 2013 Expression of Concern raised issues involving adverse-event reporting, informed consent at one site, and blinding integrity. These unresolved reporting and conduct issues reduce confidence in the trial’s benefit and safety estimates.

TIPO-1 integrity notice · adverse events and conduct

Journal integrity notice

The Lancet, 2013

The journal attached an Expression of Concern to the 2008 tesofensine trial after issues were raised about adverse-event reporting, informed consent at one site, and blinding.

Participants / model: TIPO-1 publication and conduct
Treatment: No treatment intervention
Follow-up: Published 2013
Study design: Expression of Concern

The notice does not retract the result, but it lowers confidence in both efficacy and safety interpretation.

Read the original source

TIPO-1 · underreporting letter

Journal correspondence

The Lancet, 2013

Correspondence documents the dispute around adverse-event reporting and trial conduct linked to TIPO-1.

Participants / model: TIPO-1 trial record
Treatment: No intervention
Follow-up: 2013 correspondence
Study design: Journal letter linked to Expression of Concern

Correspondence is context for integrity concerns, not a separate efficacy estimate.

Read the original source

What has the Mexican phase 3 program reported?

A company report describes 24-week mean weight changes of -2.23% with placebo, -6.22% with 0.25 mg, and -9.72% with 0.5 mg. The WHO trial registry documents the study design; the cited records do not provide a full peer-reviewed phase 3 outcome paper.

The registry provides summary results; a full methods and safety report was not found.

Mexican phase 3 · registry result

Regulator trial-registry summary

COFEPRIS, protocol registry

The registry summary reports mean 24-week weight changes of -2.23%, -6.22%, and -9.72% for placebo, 0.25 mg, and 0.5 mg.

Participants / model: Adults enrolled in the Mexican obesity program
Treatment: Tesofensine 0.25 or 0.5 mg or placebo
Follow-up: 24 weeks
Study design: Phase 3 registry result

The cited records describe the trial design and sponsor-reported outcome but do not provide a full peer-reviewed phase 3 report.

Read the original source

Is tesofensine approved in Mexico or the United States?

The cited US records list no FDA-approved tesofensine drug. The cited COFEPRIS record covers an application and resubmission, not final authorization in Mexico.

The Mexican program’s trial registration and company reporting establish that the program exists, while the cited regulatory record documents application activity rather than final authorization.

Tesofensine status · Mexico and U.S.

US and Mexican approval status

Drugs@FDA, openFDA, and COFEPRIS records.

No FDA-approved tesofensine drug appears in the cited US approval records. The cited COFEPRIS record covers an application and resubmission rather than final authorization.

Read the original source

Saniona Q1 · Mexican application process

Company financial report

Saniona, May 2026

Saniona described the Mexican application and partner process without presenting a final marketing authorization.

Participants / model: Tesofensine Mexican program
Treatment: Medix application process
Follow-up: Status through first quarter 2026
Study design: Company regulatory update

The company report describes the application process and does not contain a final authorization.

Read the original source

Can Tesomet prove tesofensine alone is cardiovascularly neutral?

TIPO-1 found a 7.4-beat-per-minute increase at 0.5 mg. A later 37-person study added metoprolol to limit that effect and stopped after two participants developed prolonged tachycardia above 120 beats per minute. It cannot establish cardiovascular neutrality for tesofensine alone.

Tesomet contains a beta blocker. Its results cannot be assigned to tesofensine monotherapy.

TIPO-1 · efficacy and heart rate

Randomized trial under Expression of Concern

Astrup et al., The Lancet, 2008

In 203 adults, tesofensine produced dose-related 24-week weight loss; the 0.5 mg arm increased heart rate by 7.4 beats per minute.

Participants / model: Adults with BMI 30 to 40
Treatment: Tesofensine 0.25, 0.5, or 1.0 mg daily or placebo, all with diet
Follow-up: 24 weeks
Study design: Randomized, double-blind, placebo-controlled phase 2 trial

The paper carries a 2013 Expression of Concern that materially limits confidence.

Read the original source

Tesofensine heart-rate study · tachycardia halt

Registry results

ClinicalTrials.gov, NCT03488719

The 37-person study tested metoprolol mitigation of tesofensine-related heart-rate effects and was halted after two prolonged tachycardia events.

Participants / model: Healthy or eligible phase 1 participants
Treatment: Tesofensine alone and with randomized metoprolol doses
Follow-up: About 23 treatment days
Study design: Phase 1 pharmacodynamic interaction study

Metoprolol-containing results do not establish tesofensine monotherapy safety.

Read the original source

What did the small Tesomet trial show?

Tesomet combines 0.5 mg tesofensine with 50 mg metoprolol. In 21 adults with hypothalamic obesity, 24-week additional mean weight change versus placebo was -6.3 percentage points. The trial was limited to 21 people with hypothalamic obesity.

The result supports study of the combination in hypothalamic obesity. It does not settle general-obesity efficacy or monotherapy safety.

Tesomet · 21-person hypothalamic-obesity trial

Randomized trial

Højgaard et al., Endocrine Connections, 2022

In 21 adults, Tesomet produced an additional -6.3 percentage points of weight change versus placebo over 24 weeks.

Participants / model: Adults with hypothalamic obesity
Treatment: Tesofensine 0.5 mg plus metoprolol 50 mg or placebo
Follow-up: 24 weeks
Study design: Randomized, placebo-controlled trial

Only 21 people with hypothalamic obesity were studied, and treatment included metoprolol.

Read the original source

How do tesofensine, tesofensine citrate, Tesomet, and M1 differ?

Tesofensine is the parent active moiety. A citrate salt changes the mass relationship, Tesomet adds metoprolol, and M1 is an active metabolite. Studies of the combination or metabolite cannot be read as studies of tesofensine alone.

A result from the free substance cannot be copied to a citrate product by matching milligrams without a defined salt conversion and formulation.

TIPO-1 · efficacy and heart rate

Randomized trial under Expression of Concern

Astrup et al., The Lancet, 2008

In 203 adults, tesofensine produced dose-related 24-week weight loss; the 0.5 mg arm increased heart rate by 7.4 beats per minute.

Participants / model: Adults with BMI 30 to 40
Treatment: Tesofensine 0.25, 0.5, or 1.0 mg daily or placebo, all with diet
Follow-up: 24 weeks
Study design: Randomized, double-blind, placebo-controlled phase 2 trial

The paper carries a 2013 Expression of Concern that materially limits confidence.

Read the original source

Tesomet · 21-person hypothalamic-obesity trial

Randomized trial

Højgaard et al., Endocrine Connections, 2022

In 21 adults, Tesomet produced an additional -6.3 percentage points of weight change versus placebo over 24 weeks.

Participants / model: Adults with hypothalamic obesity
Treatment: Tesofensine 0.5 mg plus metoprolol 50 mg or placebo
Follow-up: 24 weeks
Study design: Randomized, placebo-controlled trial

Only 21 people with hypothalamic obesity were studied, and treatment included metoprolol.

Read the original source

How complete is the neuropsychiatric and long-term safety record?

A monoamine reuptake inhibitor requires careful assessment of sleep, mood, anxiety, blood pressure, pulse, interacting medicines, and discontinuation. The old phase 2 report, integrity concerns, registry-level phase 3 summary, and small beta-blocker study do not provide a modern long-term outcomes database.

TIPO-1 · efficacy and heart rate

Randomized trial under Expression of Concern

Astrup et al., The Lancet, 2008

In 203 adults, tesofensine produced dose-related 24-week weight loss; the 0.5 mg arm increased heart rate by 7.4 beats per minute.

Participants / model: Adults with BMI 30 to 40
Treatment: Tesofensine 0.25, 0.5, or 1.0 mg daily or placebo, all with diet
Follow-up: 24 weeks
Study design: Randomized, double-blind, placebo-controlled phase 2 trial

The paper carries a 2013 Expression of Concern that materially limits confidence.

Read the original source

TIPO-1 integrity notice · adverse events and conduct

Journal integrity notice

The Lancet, 2013

The journal attached an Expression of Concern to the 2008 tesofensine trial after issues were raised about adverse-event reporting, informed consent at one site, and blinding.

Participants / model: TIPO-1 publication and conduct
Treatment: No treatment intervention
Follow-up: Published 2013
Study design: Expression of Concern

The notice does not retract the result, but it lowers confidence in both efficacy and safety interpretation.

Read the original source

Tesofensine heart-rate study · tachycardia halt

Registry results

ClinicalTrials.gov, NCT03488719

The 37-person study tested metoprolol mitigation of tesofensine-related heart-rate effects and was halted after two prolonged tachycardia events.

Participants / model: Healthy or eligible phase 1 participants
Treatment: Tesofensine alone and with randomized metoprolol doses
Follow-up: About 23 treatment days
Study design: Phase 1 pharmacodynamic interaction study

Metoprolol-containing results do not establish tesofensine monotherapy safety.

Read the original source

Studies and sources

TIPO-1 · efficacy and heart rate

Randomized trial under Expression of Concern

Astrup et al., The Lancet, 2008

In 203 adults, tesofensine produced dose-related 24-week weight loss; the 0.5 mg arm increased heart rate by 7.4 beats per minute.

Participants / model: Adults with BMI 30 to 40
Treatment: Tesofensine 0.25, 0.5, or 1.0 mg daily or placebo, all with diet
Follow-up: 24 weeks
Study design: Randomized, double-blind, placebo-controlled phase 2 trial

The paper carries a 2013 Expression of Concern that materially limits confidence.

Read the original source

TIPO-1 integrity notice · adverse events and conduct

Journal integrity notice

The Lancet, 2013

The journal attached an Expression of Concern to the 2008 tesofensine trial after issues were raised about adverse-event reporting, informed consent at one site, and blinding.

Participants / model: TIPO-1 publication and conduct
Treatment: No treatment intervention
Follow-up: Published 2013
Study design: Expression of Concern

The notice does not retract the result, but it lowers confidence in both efficacy and safety interpretation.

Read the original source

TIPO-1 · underreporting letter

Journal correspondence

The Lancet, 2013

Correspondence documents the dispute around adverse-event reporting and trial conduct linked to TIPO-1.

Participants / model: TIPO-1 trial record
Treatment: No intervention
Follow-up: 2013 correspondence
Study design: Journal letter linked to Expression of Concern

Correspondence is context for integrity concerns, not a separate efficacy estimate.

Read the original source

Mexican phase 3 · registry result

Regulator trial-registry summary

COFEPRIS, protocol registry

The registry summary reports mean 24-week weight changes of -2.23%, -6.22%, and -9.72% for placebo, 0.25 mg, and 0.5 mg.

Participants / model: Adults enrolled in the Mexican obesity program
Treatment: Tesofensine 0.25 or 0.5 mg or placebo
Follow-up: 24 weeks
Study design: Phase 3 registry result

The cited records describe the trial design and sponsor-reported outcome but do not provide a full peer-reviewed phase 3 report.

Read the original source

Tesofensine status · Mexico and U.S.

US and Mexican approval status

Drugs@FDA, openFDA, and COFEPRIS records.

No FDA-approved tesofensine drug appears in the cited US approval records. The cited COFEPRIS record covers an application and resubmission rather than final authorization.

Read the original source

Saniona Q1 · Mexican application process

Company financial report

Saniona, May 2026

Saniona described the Mexican application and partner process without presenting a final marketing authorization.

Participants / model: Tesofensine Mexican program
Treatment: Medix application process
Follow-up: Status through first quarter 2026
Study design: Company regulatory update

The company report describes the application process and does not contain a final authorization.

Read the original source

Tesofensine heart-rate study · tachycardia halt

Registry results

ClinicalTrials.gov, NCT03488719

The 37-person study tested metoprolol mitigation of tesofensine-related heart-rate effects and was halted after two prolonged tachycardia events.

Participants / model: Healthy or eligible phase 1 participants
Treatment: Tesofensine alone and with randomized metoprolol doses
Follow-up: About 23 treatment days
Study design: Phase 1 pharmacodynamic interaction study

Metoprolol-containing results do not establish tesofensine monotherapy safety.

Read the original source

Tesomet · 21-person hypothalamic-obesity trial

Randomized trial

Højgaard et al., Endocrine Connections, 2022

In 21 adults, Tesomet produced an additional -6.3 percentage points of weight change versus placebo over 24 weeks.

Participants / model: Adults with hypothalamic obesity
Treatment: Tesofensine 0.5 mg plus metoprolol 50 mg or placebo
Follow-up: 24 weeks
Study design: Randomized, placebo-controlled trial

Only 21 people with hypothalamic obesity were studied, and treatment included metoprolol.

Read the original source

Why is Tesofensine in B tier?

B tier reflects reported weight loss in randomized trials. Confidence is limited by the TIPO-1 Expression of Concern and because the Mexican phase 3 outcomes come from a company report rather than a full peer-reviewed report.