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Tesofensine vs GLP-1 Agonists vs Sympathomimetics: Mechanism and Outcome Comparison
Tesofensine (1.0mg) Triple monoamine reuptake inhibition (dopamine, norepinephrine, serotonin) 10.6% 80–85% fat, 15–20% lean +10% Mild tachycardia (+7 bpm), mild BP elevation (+3.5 mmHg systolic) Most potent single-agent weight loss in human trials; cardiovasc
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- Tesofensine (1.0mg)
- Triple monoamine reuptake inhibition (dopamine, norepinephrine, serotonin)
- 10.6%
- 80–85% fat, 15–20% lean
- +10%
- Mild tachycardia (+7 bpm), mild BP elevation (+3.5 mmHg systolic)
- Most potent single-agent weight loss in human trials; cardiovascular monitoring required
- Semaglutide (2.4mg weekly)
- GLP-1 receptor agonist; slows gastric emptying, enhances satiety
- 14.9% (68 weeks)
- 70–75% fat, 25–30% lean
- No significant change or slight decrease
- Minimal; rare cases of gallbladder disease
- Superior long-term weight loss; slower onset; GI side effects limit tolerability in 20–30%
- Phentermine (37.5mg)
- Norepinephrine releaser; appetite suppression via sympathomimetic effects
- 5–8% (12 weeks)
- 60–70% fat, 30–40% lean
- +3–5%
- Moderate tachycardia, elevated BP, contraindicated in cardiovascular disease
- Short-term efficacy; tolerance develops; not suitable for long-term use
- Orlistat (120mg TID)
- Pancreatic lipase inhibitor; blocks dietary fat absorption
- 3–5% (24 weeks)
- 65–75% fat, 25–35% lean
- No change
- None (GI side effects primary)
- Modest efficacy; GI tolerability poor; compliance low due to fat malabsorption symptoms