Tesofensine: A Pill With a Heart Rate Problem and No Approval I Could Find

01What it is

Almost everything else in this reference is an injectable peptide, and nothing in that literature transfers to tesofensine. It is a small molecule, PubChem CID 11370864, formula C17H23Cl2NO, molecular weight 328.3, and its 8-azabicyclo[3.2.1]octane core is the tropane skeleton, the same scaffold family as cocaine. It blocks reuptake of noradrenaline, serotonin and dopamine at once, leaving more of each in the gap between one nerve cell and the next.

Lehr and colleagues, modelling from 320 Alzheimer patients on multiple oral doses, put the terminal half-life at 234 hours, about ten days (PMID 17324246).

02What the trials found

Under the code NS-2330, Boehringer Ingelheim ran it at neurology. Hauser and colleagues randomised 261 people with early Parkinson disease to 0.25, 0.5 or 1.0 mg orally once daily or placebo for 14 weeks, NCT00148486, and at week 14 none of the three doses separated from placebo on total UPDRS (PMID 17149725). UPDRS is how clinicians score Parkinson symptoms, so the drug did not beat a dummy pill at what it was given for. The Alzheimer arm, NCT00153010, ran 430 participants across 87 sites from February 2003. Neither indication produced a drug.

Then somebody pooled the weight data off those trials. Astrup and colleagues, Obesity 2008: plus 0.5 percent on placebo against minus 0.5, minus 0.9, minus 1.8 and minus 2.8 percent across ascending doses through 1.0 mg orally once daily over 14 weeks, P = 0.015 (PMID 18356831). Heart rate across those same doses ran minus 0.4, 2.1, 4.2, 6.0 and 6.8 bpm. Blood pressure did not move. Both of the signals that decided this compound's life arrived in one table, in patients being treated for something else.

Then the trial everything rests on, TIPO-1. Astrup and colleagues, The Lancet 2008. Five Danish obesity centres, 203 obese patients with BMI 30 to 40, all on an energy restricted diet, randomised to 0.25 mg (n=52), 0.5 mg (n=50), 1.0 mg (n=49) or placebo (n=52) orally once daily for 24 weeks, 161 completing. Diet plus placebo gave 2.0 percent weight loss. Diet plus drug gave 4.5, 9.2 and 10.6 percent, at p below 0.0001 (PMID 18950853). Registered as NCT00394667, with no results posted. The 10.6 percent every vendor page inherits came from the 1.0 mg arm.

03Why it never became an American drug

Not for want of a regulator's blessing. On 8 June 2009 NeuroSearch announced an End of Phase II meeting with FDA covering four placebo-controlled studies totalling approximately 5,700 obese patients, with 0.25 mg or 0.5 mg once daily endorsed. Look at what dropped out at that meeting: 1.0 mg, the biggest weight loss and the dose carrying the blood pressure signal.

Then the money went. On 29 October 2014 NeuroSearch transferred NS2359 and NS2330 to Saniona with no upfront cash and only milestones and royalties of up to 20 percent, after years of failing to raise capital or find a partner. Sitting behind that transfer is sibutramine, the closest marketed comparator, same class of cardiovascular signal, withdrawn in 2010 after the SCOUT outcomes trial. I found no FDA approval in any indication, though the FDA pages I needed for compounding status returned 404 or 403.

04Mexico, and the approval sentence you will see quoted

The only phase 3 ever conducted was VIKING, run by Medix in Mexico from August 2017: 372 patients randomised to oral tesofensine 0.25 mg, 0.50 mg or placebo once daily for 24 weeks, all on diet and exercise. Saniona's release of 17 December 2018 reported both doses beating placebo at p below 0.001, more than half of patients losing over ten per cent, a low but statistically significant heart rate increase, and no significant effect on blood pressure at any dose tested.

I queried ClinicalTrials.gov by intervention and by term and read every sponsor field; no Medix record, no VIKING record, no Mexican site, and the complete PubMed set for tesofensine contains no publication of it.

Medix filed with COFEPRIS in December 2019 and refiled in May 2024. COFEPRIS is the Mexican medicines regulator, and a registro sanitario is the licence it grants. In February 2023 the Comite de Moleculas Nuevas issued a favourable opinion with qualifications on tesofensina, Saniona announced it on 25 February 2023, and Mexican outlets ran it in mid-March under headlines using the verb aprueba, which is where the confusion starts, because Saniona's own description is that it does not represent a market authorization nor a rejection, and is a non-binding technical opinion. On 6 November 2024 Saniona announced that Medix had not received approval. On 20 February 2025 it announced a resubmission, a dossier of approximately 20,000 pages, and its releases from May 2025 onward do not mention tesofensine, Medix, COFEPRIS or Mexico.

Then the sentence mirrored everywhere, from superpower.com, uncited: "Approved in Mexico as Tesomet (tesofensine plus metoprolol) and Nupenta (tesofensine monotherapy) for obesity management since 2023." Tesomet is Saniona's development name, not a marketing authorisation, and Nupenta is a pantoprazole brand from Macleods Pharmaceuticals in India.

05How it compares

The rows below the top one are injections that copy a gut hormone. Tesofensine is a swallowed drug that works on the brain's own signalling chemicals, and its open question is what it does to the heart rather than what it prevents. None of the evidence below travels up.

06Where the dose came from

The convention is 0.25 mg to 0.5 mg taken orally once daily, and vendors sell 250 microgram and 500 microgram capsules and tablets. Convention, not a recommendation, and unusually here the number is not invented: it is the trial dose. Every trial paired the drug with an energy restricted diet, the phase 3 with diet and exercise, so I could find nothing published on what it does alone, and they all ran 24 weeks and stopped. The 234 hour half-life also means daily dosing keeps accumulating for roughly six to eight weeks, so a protocol judging a dose at two weeks is reading it before the drug has finished arriving.

07What could go wrong

Read the TIPO-1 cardiovascular sentence for what it leaves out. It clears 0.25 and 0.5 mg on systolic and diastolic blood pressure against placebo, concedes heart rate up 7.4 beats per minute at 0.5 mg, and says nothing at all about the 1.0 mg arm, the one that produced the 10.6 percent. Bello and Zahner's 2009 review of the programme fills the hole: dose-dependent heart rate elevations, with significant blood pressure increases at the highest dose tested (PMID 19777399). Secondary sources put the 1.0 mg arm at 6.8/5.8 mm Hg and 8.5 bpm, but the Lancet full text returned 403 to me, so treat those two as unverified against the paper.

Then 2013. An Expression of Concern is what a journal attaches when a paper is unresolved and it will not withdraw it. After a Danish Health and Medicines Authority inspection of the completed trial, The Lancet attached an Expression of Concern: consent delegated to non-medical personnel at one site, blinding integrity questioned in an earlier 2007 inspection, and monitors instructing investigators not to record headache, migraine, stress and depression as adverse events when a patient had reported those conditions before randomisation (PMID 23561987). The investigators replied, and the title of the reply is the admission: "Under-reporting of adverse effects of tesofensine" (PMID 23849924). I found it still standing, with no closure or retraction notice.

Tesomet gets cited to close the blood pressure question, so keep it separate. It is a fixed co-administration of 0.5 mg tesofensine with 50 mg metoprolol, a beta blocker put there to cancel the cardiovascular effect, after work in conscious telemetered rats showed oral metoprolol at 10 to 20 mg/kg doing exactly that while leaving the appetite suppression intact (PMID 23784901). Huynh and colleagues ran that combination against placebo orally once daily for 24 weeks in 21 adults with hypothalamic obesity and found no significant difference between groups in heart rate or blood pressure (PMID 35294397). That flat result belongs to the combination, not to the pill on its own.

08What nobody knows

What it does to the heart at the dose that took off the most weight. The trial built to settle it, NCT00481104, 140 obese patients with a primary outcome of vital signs, has no results posted.

What is in a capsule bought off a vendor, and what it has done to anybody. I found no published case report of harm from a grey market tesofensine product, and no independent analysis of one.

09My take

This is the only compound here where the circulating dose is the real trial dose, and it is still the one I would be most careful with, because what stopped it was never the weight loss. FDA endorsed a phase 3, the dose that worked best was dropped on the way into it, the company could not fund the trial, and the pivotal paper now sits under an Expression of Concern specifically about adverse events going unrecorded, which is a bad place for a paperwork problem in a drug whose open question is cardiovascular. The one modern trial with clean blood pressure numbers is a trial of two drugs.

If you have seen tesofensine sold with a Mexican approval claimed on the listing, what exactly did it say, and was a registro sanitario number attached?

Frequently asked

Is tesofensine approved anywhere?+

I could not find a marketing authorisation in any country, and I found no FDA approval in any indication.

Is tesofensine approved in Mexico?+

As of 5 August 2026 I could not find evidence that a registro sanitario, the Mexican marketing licence, has been granted, and I am not asserting that none has. In November 2024 the sponsor announced that the filing had not been approved.

How much weight did people lose on tesofensine?+

In the one published obesity trial, 203 obese patients at five Danish centres were randomised to one of three doses or to a dummy pill for 24 weeks, all of them on an energy restricted diet. Diet plus placebo gave 2.0 percent of body weight. Diet plus drug gave 4.5, 9.2 and 10.6 percent across ascending doses.

Does tesofensine raise heart rate?+

The obesity trial conceded a rise of 7.4 beats per minute at its middle dose and said nothing at all about the highest one, the arm that produced the largest weight loss.

Why does the tesofensine paper carry an Expression of Concern?+

The Lancet attached one in 2013, after a Danish Health and Medicines Authority inspection of the completed trial. The investigators replied under the title Under-reporting of adverse effects of tesofensine.

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This content is for educational and informational purposes only and is not medical advice. Peptides discussed are research compounds and may not be approved for human use. Nothing here should be used to diagnose, treat, cure, or prevent any disease. Always consult a qualified healthcare professional before starting any peptide, supplement, or protocol. Individual responses vary. Do not self-administer compounds without proper medical supervision.