Orforglipron vs Tesofensine
Side-by-side comparison of key properties, dosing, and research.
GLP-1 / Weight Loss Agonists
OrforglipronFat Loss & Metabolic
Tesofensine- Summary
- Orforglipron is an oral, once-daily small-molecule GLP-1 receptor agonist developed by Eli Lilly. Unlike injectable GLP-1 peptides, it is a non-peptide compound absorbed orally without food restrictions, representing a major convenience advancement. Phase 2 trials showed up to 9.4% weight loss at 36 weeks, and Phase 3 trials (ATTAIN program) are ongoing for obesity and type 2 diabetes.
- Tesofensine is a triple monoamine reuptake inhibitor (TMRI) that blocks reuptake of serotonin, dopamine, and norepinephrine. Originally developed for Alzheimer's and Parkinson's disease, it was repurposed as a potent weight loss agent after clinical trials demonstrated substantial fat loss via appetite suppression and increased energy expenditure.
- Half-Life
- ~12 hours (once-daily oral dosing)
- 8-10 days (exceptionally long; accumulates over weeks)
- Admin Route
- Oral
- Oral
- Research
- —
- —
- Typical Dose
- 12 mg → 24 mg → 36 mg → 45 mg
- 0.25-0.5 mg per day
- Frequency
- Once daily
- Once daily
- Key Benefits
- Oral pill — no injections required
- Once-daily dosing without food restrictions (unlike oral semaglutide)
- Up to 9.4% body weight reduction in Phase 2 at 36 weeks
- Significant HbA1c reduction in type 2 diabetes trials
- Small-molecule stability — no cold chain requirements
- Broadens access for injection-averse patients
- Potential class-defining convenience advantage over injectable GLP-1s
- Potent appetite suppression via triple monoamine reuptake inhibition
- Significant weight loss (8-12% body weight in phase II trials at 0.5 mg)
- Increases basal metabolic rate and energy expenditure
- Reduces fat mass preferentially over lean mass
- Potential cognitive benefit via dopaminergic and noradrenergic enhancement
- Longer half-life than sibutramine allows once-daily dosing
- Side Effects
- Nausea (most common, dose-dependent)
- Vomiting
- Diarrhea
- Decreased appetite
- +2 more
- Elevated heart rate and blood pressure (sympathomimetic)
- Dry mouth
- Insomnia and sleep disturbances
- Nausea
- +4 more
- Stacks With
- —
- —