Retatrutide: The Triple Agonist

Both are Eli Lilly products and share GIP and GLP-1 activity. Retatrutide adds a third mechanism — glucagon receptor activation — which increases energy expenditure and enhances liver fat burning. This triple action produces higher weight loss numbers (~29% vs. ~22-26%).

Retatrutide is currently in Phase 3 trials. FDA approval is projected for approximately 2027, with market launch expected shortly after. Results from the key TRIUMPH studies are expected throughout 2026.

The weight loss observed with retatrutide occurs gradually over 68+ weeks and is associated with improvements in metabolic markers, blood pressure, and inflammatory markers. Physicians will monitor patients closely, and dose adjustments can be made. Some TRIUMPH-4 participants discontinued treatment due to perceived excessive weight loss, highlighting the potency.

Dysesthesia is an abnormal sensation where normal touch feels unusual or uncomfortable. It was reported in up to 20.9% of patients on the highest dose. While the signal warrants monitoring, it did not appear to cause treatment discontinuation in the trial. More data is expected from additional Phase 3 studies.

They take different approaches: retatrutide activates GIP + GLP-1 + glucagon receptors, while CagriSema combines amylin + GLP-1 signaling. Phase 3 data suggests retatrutide may produce slightly higher weight loss (~29% vs. ~23%), but no head-to-head trial exists. The choice will likely depend on individual patient factors and tolerability.