💉 Retatrutide: The Triple Threat That Could Reshape Obesity Care

 I just finished reading the full NEJM article on Retatrutide, the new triple-agonist weight-loss medication in development by Eli Lilly, and it’s one of the most compelling studies I’ve seen in a while.

To be clear—this drug isn’t approved yet, but what the data shows is significant. If you’ve been following the incretin class of medications like I have (Zepbound, Wegovy, Mounjaro), this one raises the bar.

Here’s the science in plain terms:

🧬 What is Retatrutide?
It’s a once-weekly injectable that targets three receptors:

• GLP-1 (reduces appetite, improves glucose control)

• GIP (enhances insulin, may impact fat metabolism)

• Glucagon receptor (triggers fat burning by increasing energy output)

Zepbound only hits GLP-1 and GIP. Adding the glucagon receptor into the mix is what makes Retatrutide so interesting—this third pathway could be why the results are so much more dramatic.

📊 Study Overview:

• 338 adults with obesity or overweight (no diabetes)

• Weekly injections of Retatrutide or placebo for 48 weeks

• Tracked for weight loss and metabolic improvements

📉 The Results:

• At the highest dose, the average weight loss was 24.2% at week 48.

• People were still losing weight steadily at week 48—not plateauing yet.

• Lower doses also led to strong, dose-dependent results.

• Participants showed improved liver fat content, blood pressure, and lipid panels.

🤢 Side effects were mostly mild GI symptoms—nausea, vomiting, diarrhea—similar to what you see with all GLP-1s. They tapered off over time.  When I try it, I should be OK. Had GI symptoms on Saxenda in 2019 but MJ and Zep have been great for me.  145 weeks and only 4 days of intense diarrhea and constipation would be constant if I didn’t manage it with enzymes.

🧠 As someone who is data driven and a slow responder to tirzepatide, this study genuinely excites me. I’ve been on Zepbound for nearly three years. It’s working—slowly—but not with the jaw-dropping speed that some others experience. I’ve always suspected that my system just needs a stronger metabolic nudge. Retatrutide might be that nudge.

The idea of targeting appetite regulation, insulin dynamics, and fat-burning energy signaling in one shot is not just innovative—it could be a game changer for people like me whose biology doesn’t follow the “eat less, move more” script.

I’ll be watching the ongoing trials closely, and if it gets FDA approval in the next year or two, I’ll absolutely be discussing it with my care team. There’s no magic bullet, but there are better tools emerging—and that gives me hope.

If you want to dig into the actual study, here’s the link:
📄 https://www.nejm.org/doi/full/10.1056/NEJMoa2301972