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TesofensineSmall moleculeNo amino acid sequence. Icon reflects category theme only.Also known as: NS-2330, NS2330, Tesomet (combination with metoprolol)
In a Phase 2 trial of 203 obese adults, tesofensine at 0.5 mg produced 9.2% mean body weight loss in 24 weeks (Lancet 2008)[1]. That's from a once-daily oral capsule, not an injection. Tesofensine is a triple monoamine reuptake inhibitor that blocks serotonin, norepinephrine, and dopamine reuptake in brain feeding circuits. It isn't FDA-approved, and the primary trial carries a 2013 Expression of Concern for adverse event under-reporting. The compound is furthest along in Mexico, where Medix submitted a regulatory dossier to COFEPRIS in early 2025. People reach for it when GLP-1 side effects are intolerable or when they want a CNS-based approach to appetite control.
A Phase 2 trial of 203 adults showed 9.2% placebo-adjusted weight loss at 0.5 mg over 24 weeks. The 1.0 mg group hit 10.6%. Those numbers turned heads because no oral drug at the time came close. Tesofensine (NS-2330, CAS 195875-84-4) is a triple monoamine reuptake inhibitor. It blocks reuptake of serotonin, norepinephrine, and dopamine simultaneously in the brain. That triple action separates it from older appetite suppressants like sibutramine, which hit only two of the three monoamines. NeuroSearch originally developed it for Alzheimer's and Parkinson's disease; the weight loss showed up as an unintended finding in those trials (Obesity 2008)[2]. The mechanism is straightforward. Blocking monoamine reuptake increases neurotransmitter levels in hypothalamic feeding circuits. Recent work confirmed tesofensine silences GABAergic neurons in the lateral hypothalamus that normally drive eating behavior (PLoS One 2024)[3]. There may also be a modest thermogenic effect from increased resting energy expenditure. Practically, it's one capsule per morning. The half-life sits around 9 days, so a missed dose barely registers. Saniona's partner Medix completed Phase 3 in Mexico and submitted to COFEPRIS in February 2025. No FDA or EMA applications exist. The Lancet 2008 trial [1] received an Expression of Concern in 2013 after a Danish audit found adverse events had been under-reported at some trial sites. The weight loss data wasn't questioned, but the side effect profile may understate real rates.
Tesofensine blocks three presynaptic transporters: the norepinephrine transporter (NET), serotonin transporter (SERT), and dopamine transporter (DAT). In vitro IC50 values land at 1.7 nM for norepinephrine, 6.5 nM for dopamine, and 11 nM for serotonin. That ranking matters; the strongest binding affinity is at the norepinephrine transporter. Blocking all three raises extracellular monoamine concentrations in hypothalamic feeding circuits. The downstream effect: alpha-1 adrenoceptor and dopamine D1 receptor activation in the hypothalamus produces satiety (Neuropsychopharmacology 2010)[4]. A 2024 study mapped this further, confirming tesofensine silences a specific subset of GABAergic neurons in the lateral hypothalamus that normally promote feeding (PLoS One 2024)[3]. That's a direct neuronal off-switch for hunger drive. CYP3A4 handles metabolism. The primary active metabolite, M1, retains monoamine reuptake inhibition and has a half-life of roughly 16 days. Between the parent compound (~9 days) and M1, pharmacological activity persists for weeks beyond the last dose. Population PK modeling by Lehr and colleagues confirmed the 234-hour mean half-life (Br J Clin Pharmacol 2007)[5]. A modest increase in resting energy expenditure may add a thermogenic component on top of the appetite suppression.
Phase 2 (Lancet 2008)[1] and Phase 3 Viking (Mexico) trials confirm ~9.2% placebo-adjusted body weight loss at 0.5 mg over 24 weeks. Confidence is moderate, not strong, because the primary Lancet 2008 trial carries a 2013 Expression of Concern for adverse event under-reporting at some sites.
Lancet 2008 (PMID 18950853); Phase 3 Viking trial (Mexico)
Lancet 2008 Expression of Concern for adverse event under-reporting. 1.0 mg dose dropped from Phase 3 due to higher cardiovascular burden. No FDA or EMA approval.
Oral weight loss peptide used at 0.5 mg/day. Community reports meaningful appetite suppression and mood elevation. Cycling 8-12 weeks on / 4 weeks off is standard.
Community dose (0.5 mg/day AM) precisely matches Phase 3 primary dose. Reported side effects (dry mouth, HR elevation, insomnia) map directly to clinical trial data. Community cycling (8–12 weeks) is shorter than the 24-week trial protocol, reflecting precautionary practice given unapproved status and cardiovascular monitoring concerns.
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 0.25mg | Daily |
| Moderate | 0.5mg | Daily |
| Aggressive | 1mg | Daily |
This one is oral, not injectable. No reconstitution math, no bacteriostatic water, no syringes. You're taking a capsule each morning. Start at 0.25 mg daily for the first 2 to 4 weeks. The half-life is around 9 days, so you won't reach steady state until roughly week 4 or 5. Don't judge whether it's working before then. The active metabolite M1 has a 16-day half-life on top of that. Effects build slowly and linger long after your last dose. Take it before 9 AM. This is non-negotiable if you value sleep. Even noon dosing causes insomnia for most people. Monitor your resting heart rate at baseline and weekly for the first month. If it jumps more than 10 bpm or crosses 100 bpm, hold at the current dose and reassess. Don't rapidly stop and restart; the long half-life means plasma levels shift very slowly. Gray-market sourcing is the current reality. No US compounding pharmacy pathway exists. Verify lot-specific COAs with HPLC purity data before buying anything.
Clinical trials administered tesofensine continuously for 24 weeks. Long-term cycling data beyond 24 weeks is limited. Work with a prescribing physician to determine duration of use. The long half-life (~9 days) means pharmacological effects persist for several weeks after the last dose.
Clinical trials ran tesofensine continuously for 24 weeks with no receptor desensitization or efficacy loss observed. Cycling is not evidence-based for efficacy: it is driven by precautionary safety considerations: long-term safety beyond 24 weeks is absent; the drug is unapproved; the Expression of Concern on the primary trial means the true AE burden may be understated; and cardiovascular effects warrant periodic off-drug assessment.
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Expected: ~9–11% total body weight loss at 24 weeks based on Phase 2/3 clinical data
Monitor: Baseline HR and BP before starting. Recheck at 2 and 4 weeks. Hold/reduce dose if resting HR >100 bpm or BP rises >10 mmHg systolic.
Obtain tesofensine capsules from a verified source with lot-specific third-party certificates of analysis. Confirm capsule dose matches the label (0.25 mg or 0.5 mg).
With or without food; pharmacokinetics don't change between fed and fasted states.
This is the titration window. Assess tolerability by tracking resting heart rate, dry mouth severity, and sleep quality.
If tolerated, increase to one 0.5 mg capsule daily in the morning. This is the therapeutic dose based on Phase 2 and Phase 3 trial data.
Maintain 0.5 mg daily for up to 24 weeks (clinical protocol) or 8 to 12 weeks (community cycling protocol).
Monitor resting heart rate weekly for the first 4 weeks, then monthly. Check blood pressure at baseline, week 4, and week 8. Track body weight weekly under the same conditions.
The 1.0 mg dose was dropped from Phase 3 specifically because of raised cardiovascular adverse events.
Store capsules at room temperature (15 to 30 degrees Celsius). No refrigeration needed.
Layered appetite suppression via complementary mechanisms: tesofensine acts centrally via monoamine reuptake inhibition; semaglutide acts via gut-brain GLP-1 signaling. Discussed in community contexts and mechanistically rational. No RCT data exists for the combination.
Tesofensine 0.5 mg/day oral + semaglutide per standard titration; monitor for additive GI effects
Same rationale as semaglutide stack. Dual GIP/GLP-1 agonism adds gut-hormone signaling to tesofensine central mechanism. Community discussion only; no clinical data.
Beta-blocker co-administration blunts tesofensine-induced HR and BP elevation while preserving appetite suppression per animal studies. This is Saniona's Tesomet fixed-dose combination with FDA orphan drug designation for hypothalamic obesity (2021) and Prader-Willi syndrome (2021). Phase 2a data (PMID 35294397): 6.28% placebo-adjusted weight loss in HIO at 24 weeks, no significant HR/BP elevation.
Fixed-dose Tesomet combination: clinical trial context only; not commercially available
Absolute contraindication. Risk of serotonin syndrome and hypertensive crisis from combined monoamine potentiation.
Do not combineAdditive SERT/NET inhibition raises serotonin syndrome risk. Mechanistically direct overlap with tesofensine.
Do not combineTesofensine is CYP3A4-metabolized. Strong inhibitors substantially increase plasma concentrations of both parent compound and active metabolite M1, amplifying cardiovascular and CNS adverse effects.
Do not combineAdditive cardiovascular stimulant effects: elevated HR, BP, and arrhythmia risk. Also increased CNS overstimulation.
Do not combinePricing updated 2026-04-09
Heart rate elevation is the side effect that deserves the most attention. Phase 2 data showed increases of 5 to 7.4 bpm at 0.5 mg and 8.5 bpm at 1.0 mg. The 1.0 mg dose was dropped entirely from Phase 3 because of this cardiovascular signal plus higher dropout rates. Community users report increases ranging from 5 to 15 bpm, and anyone with baseline cardiovascular risk factors should take that seriously. There's also a credibility issue with the published safety data itself. The Lancet 2008 trial [1] received an Expression of Concern in April 2013. A Danish Health Authority audit found that adverse events, specifically headache, migraine, stress, and depression, had been incorrectly excluded at some trial sites. The weight loss data wasn't challenged. But the side effect profile from that trial may understate actual rates. Keep that in mind when reading published numbers. Dry mouth is the most common complaint at any dose. It's dose-dependent, often persistent throughout a full course, and rarely resolves at 0.5 mg. Users describe it as manageable but constant. Increased water intake and xylitol products help somewhat. Insomnia is reliably time-of-day dependent. Taking tesofensine after 9 AM significantly increases sleep disruption. Even shifting the dose from morning to midday can cause problems. This is a CNS stimulant, and the pharmacological tail is long. Nausea, constipation, and headache round out the common side effects. Frequency data from Phase 2: the withdrawal rate due to adverse events was approximately 13% with tesofensine versus 6% with placebo. At the 0.5 mg dose, no clinically meaningful blood pressure changes were observed in clinical trials. The 1.0 mg dose told a different story, with systolic and diastolic increases of 6.8/5.8 mmHg. Don't exceed 0.5 mg without physician supervision. Because tesofensine increases dopaminergic tone, theoretical concerns about mood changes and psychological dependence exist. The Danish audit specifically flagged under-reporting of stress and depression. Monitor mood throughout treatment. Contraindications: uncontrolled hypertension or tachycardia, history of cardiovascular disease, concurrent MAO inhibitors or SSRIs/SNRIs (serotonin syndrome risk), pregnancy or breastfeeding, severe hepatic impairment, seizure disorders, narrow-angle glaucoma. The SSRI/SNRI interaction is particularly important to flag. Tesofensine and any serotonergic medication together create direct mechanistic overlap for serotonin syndrome. When to stop: persistent resting heart rate above 100 bpm, blood pressure elevation exceeding 10 mmHg systolic, insomnia that doesn't resolve with morning timing, or any emerging psychiatric symptoms.
Verify Tesofensine dosing and safety with a second opinion
Tesofensine is not FDA or EMA approved. No licensed compounding pharmacy pathway exists in the US. Currently available only from gray-market "research chemical" vendors (Umbrella Labs, SwissChems, Peptide Sciences) selling capsules without GMP certification, independent third-party purity testing, or pharmaceutical-grade manufacturing standards.
| Test | When | Target |
|---|---|---|
| Resting heart rate | Baseline, then weekly for first 4 weeks, then monthly | Resting HR <100 bpm; increase ≤10 bpm from baseline |
| Blood pressure (systolic and diastolic) | Baseline, week 4, week 8, then monthly | No increase >10 mmHg systolic from baseline |
| Sleep quality (self-report) | Weekly during first 4 weeks; monthly thereafter | — |
| Mood and psychiatric symptoms | Monthly self-assessment | — |
| Body weight and waist circumference | Weekly (same scale, same conditions, same time of day) | — |
Tesofensine reliably increases HR via noradrenergic/dopaminergic stimulation. Phase 2 data: +5–7.4 bpm at 0.5 mg, +8.5 bpm at 1.0 mg. Uncontrolled tachycardia is a stopping criterion.
No significant BP elevation observed at 0.5 mg in Phase 2 (unlike 1.0 mg: +6.8/5.8 mmHg). Noradrenergic mechanism warrants monitoring regardless.
Insomnia is dose-dependent and time-of-day dependent. Early detection allows timing correction before it becomes an adherence issue.
Dopaminergic mechanism raises theoretical mood and dependence liability. Lancet 2008 Expression of Concern specifically cited under-reporting of stress and depression: these AEs may be more common than the published trial data suggests.
Primary efficacy endpoint. Due to slow onset (~4 weeks to steady state), do not evaluate efficacy before week 6.
Initiation phase. Mild appetite reduction may begin. Common early side effects include dry mouth and mild nausea. Plasma levels are building toward steady state due to the long half-life.
Appetite suppression becomes more noticeable as plasma levels approach steady state. Side effects typically begin to stabilize. Heart rate should be monitored.
Dose escalation to therapeutic level. Appetite suppression is pronounced. Early weight loss of 3-5% expected. Steady-state concentrations of both parent compound and active metabolite M1 are established.
Peak weight loss rate. Clinical trials showed approximately 9% mean weight loss at 0.5 mg by this period. Improved energy levels and reduced food cravings reported by many users.
Continued steady weight loss. Phase 2 data showed 9.2% mean body weight reduction at 24 weeks with 0.5 mg. Weight loss rate begins to plateau as a new metabolic equilibrium is reached.
Weeks 1 to 4 (0.25 mg titration): Plasma levels are climbing but well below steady state. The ~234-hour half-life means full accumulation takes 4 to 5 weeks. M1, the active metabolite, is building too. Expect mild appetite dampening by week 3, some alertness, and a slight mood lift that users describe as "stimulant quality." Dry mouth and mild nausea start in week 1 for most people. Heart rate may tick up 3 to 5 bpm. Don't evaluate whether it's working yet. Weeks 5 to 8 (0.5 mg): Near-steady-state concentrations of both parent compound and M1 are established. Appetite suppression becomes clear. Food cravings drop noticeably. Early weight loss of 2 to 5% is typical by week 8. Insomnia risk is highest during this phase if you're not strictly dosing before 9 AM. Dry mouth persists; heart rate elevation settles around 5 to 10 bpm above baseline. Weeks 9 to 16 (0.5 mg maintenance): This is the peak weight loss window. Phase 2 data showed 7 to 9% body weight reduction by week 12. Sustained appetite reduction continues. Mood improvement shows up frequently in community reports. Side effects typically plateau if your dose stays unchanged. Occasional constipation may appear. Weeks 17 to 24 (0.5 mg maintenance): The Phase 2 mean landed at 9.2% body weight reduction at 24 weeks for the 0.5 mg group. Weight loss rate slows as your body reaches a new metabolic equilibrium. Community protocols typically end by week 12, so user data at full 24 weeks is limited. Those who continue report slow ongoing loss or weight maintenance. Post-cycle (4+ weeks off): The pharmacological tail on tesofensine is long. Parent compound half-life is ~234 hours (9.75 days); M1 metabolite is ~374 hours (roughly 16 days). Full washout takes 6 to 8 weeks after the last dose. Appetite returns gradually over 2 to 4 weeks. Weight regain is likely without sustained dietary changes. Most side effects resolve within 2 to 4 weeks; dry mouth is the last to go.
Plasma levels rising but well below steady state at week 1–2 due to ~234h half-life. Active M1 metabolite also accumulating. Some pharmacological effect expected by week 3. Steady state reached ~week 4–5.
Mild appetite dampening reported. Alertness and slight mood lift noted ("stimulant quality"). Dry mouth and mild nausea begin in week 1.
Near-steady-state plasma levels of parent and M1 achieved. Clinical trial data shows pronounced appetite reduction and early weight loss by this phase.
Clear appetite suppression. Food cravings noticeably reduced. Early weight loss of 2–5% expected. Insomnia risk highest if not strictly morning-dosed.
Phase 2 data: ~7–9% body weight loss by week 12. Steady state maintained. Modest thermogenic component may contribute.
Most active weight loss period. Sustained appetite reduction. Mood improvement frequently noted. Side effects typically plateau if dose is unchanged.
Phase 2 mean: 9.2% body weight reduction (placebo-adjusted) at 24 weeks for 0.5 mg group. Weight loss rate slows as homeostatic adaptation occurs.
Community protocols typically end by week 12; limited user data at full 24 weeks. Those reporting at this phase note continued slow loss or maintenance.
Parent compound half-life ~234h (~9.75 days); M1 metabolite ~374h (~16 days). Full pharmacological washout requires 6–8 weeks after last dose.
Appetite returns gradually over 2–4 weeks. Weight regain likely without sustained dietary intervention. Most side effects resolve within 2–4 weeks.
Source: Population PK model, Lehr et al. Br J Clin Pharmacol 2007 (PMID: 17324246): 234h mean; ~220h commonly cited
Loading the interactive decay curve.
Tesofensine is not approved by the FDA, EMA, or any major regulatory agency. It holds a Phase 3 regulatory status. Saniona's partner Medix completed a Phase 3 program in Mexico and submitted the full dossier to COFEPRIS in February 2025. The initial COFEPRIS rejection was for an incomplete data package, not safety grounds. A separate FDA orphan drug pathway exists for the tesofensine plus metoprolol combination (Tesomet) in hypothalamic obesity and Prader-Willi syndrome. Saniona received FDA orphan drug designations for both indications in 2021. In the US, tesofensine is currently available only through gray-market research chemical vendors. No licensed compounding pharmacy pathway exists. Products sold by vendors like Umbrella Labs and SwissChems are not GMP-certified, not pharmaceutical grade, and not subject to FDA manufacturing oversight. WADA status: check current prohibited list. Monoamine reuptake inhibitors with stimulant properties may fall under S6 (Stimulants) depending on classification. This content is for informational purposes only and does not constitute medical advice. Consult a qualified healthcare provider before using any research compound.
Peptide Schedule Research TeamReviewed Apr 20267 Citations
