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also known as: LY3437943, Triple agonist, GLP-1/GIP/Glucagon agonist
Half-life: ~6 days
Retatrutide is a triple incretin receptor agonist targeting GLP-1, GIP, and glucagon receptors simultaneously. In Phase 2 trials, it produced the highest weight loss ever observed in a clinical trial for an obesity medication — averaging 24% body weight reduction at 48 weeks.
Mechanism of Action
Triple agonism: GLP-1R activation reduces appetite and slows gastric emptying; GIPR activation improves insulin sensitivity and reduces glucagon; GcgR activation increases energy expenditure and lipolysis (through glucagon's thermogenic and hepatic effects).
NEJM Phase 2 results (Jastreboff et al., 2023): 24.2% body weight reduction at 48 weeks with 12 mg dose — the highest ever reported for any obesity pharmacotherapy.
GH peptides preserve lean mass during aggressive weight loss from Retatrutide.
MK-677 counters muscle loss risk by elevating GH and IGF-1.
Tirzepatide is a dual GIP/GLP-1 agonist — adding Retatrutide is receptor overlap and contraindicated.
GLP-1/glucagon agonist — redundant with Retatrutide.
Overlapping GLP-1 and glucagon receptors.
Weight loss mechanisms overlap — do not combine without medical supervision.
Maintain metabolic rate during Retatrutide breaks.
AOD9604 maintains fat mobilization through β3-adrenergic paths during breaks.
Storage
Refrigerate at 2–8°C (36–46°F).
Reconstitution
Per compounding pharmacy instructions if compounded.