Side-by-side · Research reference

MK-677vsTesofensine

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

APhase 2Reviewed13/45 cited

BPhase 3Draft10/40 cited

MK-677

Oral GHS · Ibutamoren

10–25 mgDaily dose (oral)Nass 2008

Phase 2Evidence levelMurphy 1998 Nass 2008

~24 hrHalf-lifeNass 2008

Oral capsule · 1×/day

Tesofensine

SNDRI · Phase 3 obesity candidate

0.25–0.5 mgDaily doseAstrup 2008

9.2 kgWeight ↓ (24 wk)Astrup 2008

Phase 3Evidence levelAstrup 2008

Oral · Once daily morning

01Mechanism of Action

Parameter

MK-677

Tesofensine

Primary target

Ghrelin receptor (GHS-R1a)Murphy 1998

Serotonin / norepinephrine / dopamine transporters (SERT / NET / DAT)Astrup 2008

Pathway

GHS-R1a → Gαq → Ca²⁺ → sustained GH pulses across 24 hrNass 2008

Triple monoamine reuptake inhibition → ↑synaptic 5-HT, NE, DA → appetite suppression + thermogenesisAstrup 2008

Downstream effect

Sustained GH + IGF-1 elevation; appetite stimulation; lean mass preservationNass 2008

Strong appetite suppression, mild thermogenic effect, weight lossAstrup 2008

Feedback intact?

Pulsatile pattern preserved despite long half-lifeMurphy 1998

—

Origin

Non-peptide spiroindane-piperidine small molecule designed at MerckMurphy 1998

Small molecule developed by NeuroSearch (Denmark) for CNS indications, repurposed for obesityAstrup 2008

Antibody development

—

02Dosage Protocols

Parameter

MK-677

Tesofensine

Standard dose

10–25 mg / day oralNass 2008

25 mg used in Nass 2008 elderly trial; 10–15 mg common community dose.

0.25–0.5 mg / dayAstrup 2008

Frequency

Once daily, oral

Once daily, morning

Lower / starter dose

5 mg / day

0.125 mg / day

Evidence basis

Phase 2 trials (Nass 2008, Murphy 1998)Nass 2008 Murphy 1998

Phase 2b + ongoing Phase 3Astrup 2008

Duration

8–16 weeks per cycle (off-cycle to reset receptor sensitivity)

24 weeks per studied cycle

Reconstitution

Oral, no reconstitution

—

Timing

Pre-sleep preferred for natural GH pulse alignment

Morning to avoid sleep disruption

Half-life

~24 hrNass 2008

Once-daily dosing covers 24 hours.

~9 days (very long)

Form

—

Oral capsule

04Side Effects & Safety

Parameter

MK-677

Tesofensine

Increased appetite

Strong appetite increase via ghrelin agonism

—

Water retention

Mild edema, paresthesias

—

Glucose tolerance

↑ HbA1c +0.3–0.5% in 2-yr elderly trialNass 2008

—

IGF-1 elevation

+50–100% sustainedNass 2008

—

Cancer risk

Contraindicated in active malignancy (GH/IGF-1 axis)

—

Cardiovascular

No clear adverse signal in trials; congestive heart failure caution

—

Drowsiness

Common, especially during initial weeks

—

Pregnancy / OB

Avoid

Contraindicated

Heart rate / BP

—

Dose-dependent ↑ HR + BPAstrup 2008

Insomnia

—

Dose-related; mitigate with morning timing

Dry mouth

—

Common

Nausea

—

Common

Mood changes

—

Anxiety / agitation possible

Cardiovascular events

—

Phase 3 trial monitoring; not yet FDA-cleared

Absolute Contraindications

MK-677

·Active malignancy
·Pregnancy / breastfeeding
·Disrupted hypothalamic-pituitary axis
·Congestive heart failure (caution)

Tesofensine

·Pregnancy / breastfeeding
·Severe cardiovascular disease
·Concurrent MAOI use

Relative Contraindications

MK-677

·Untreated diabetes
·Pre-diabetes
·Severe insulin resistance

Tesofensine

·Hypertension
·Anxiety disorder
·Insomnia

05Administration Protocol

Parameter

MK-677

Tesofensine

1. Form

Capsule or oral solution. No injection.

Oral capsule (investigational; not commercial).

2. Site

Oral. Take with or without food.

Swallow whole with water, morning only.

3. Timing

Pre-sleep preferred — aligns with natural GH pulse.

Morning to mitigate insomnia. Do not dose evening.

4. Storage

Capsule: room temp ≤25 °C, dry place.

Room temp ≤25 °C, dry place.

5. Caveat

Monitor HbA1c every 8–12 weeks during chronic use.

Monitor BP + HR + mood. Avoid stimulants + MAOIs.