Breaking Medical News: Retatrutide results

💊 Another Nail in the Coffin for the “Willpower” Myth

Another nail in the coffin for those who think obesity is a lack of willpower—some moral failing, or simply the result of eating poorly or not getting enough exercise.

In spite of overwhelming scientific evidence, obesity remains one of the most stigmatized diseases in modern medicine. It’s highly discriminatory. I’ve spent years railing against this bias—yet even in my own family, I’ve been surprised to find that those who’ve heard me argue passionately for compassion and science over shame still harbor those old feelings.

But the data keep coming. And this week, Eli Lilly delivered a stunning piece of it.

---

🧬 A Triple-Agonist Breakthrough

Eli Lilly’s experimental drug, retatrutide, a first-in-class triple hormone receptor agonist, just posted astonishing results from the Phase 3 TRIUMPH-4 trial in adults with obesity and knee osteoarthritis. Retatrutide activates GIP, GLP-1, and glucagon receptors—earning it the “triple-G” moniker. Fierce Biotech+1

After 68 weeks of once-weekly injections:

• Participants on 12 mg lost an average of 28.7% of their body weight (~71 pounds).

• Even when accounting for patients who discontinued treatment, the weight loss remained impressive. Fierce Biotech

This crushes analyst expectations for efficacy and outpaces benchmarks set by both tirzepatide (Zepbound) and semaglutide. Reuters

---

📉 Pain, Weight, and What It Means

Beyond weight loss, retatrutide delivered a ~75% reduction in knee pain scores on the WOMAC scale—far more than the ~40% improvement in the placebo group. Fierce Biotech

Patients with severe osteoarthritis and obesity tend to spiral into immobility, pain, and worsening metabolic health. A drug that simultaneously shrinks fat, relieves pain, and improves function could be transformational for millions.

Common side effects were in line with other incretin therapies—nausea, diarrhea, constipation, and decreased appetite—but there was a higher discontinuation rate than in earlier trials and than placebo. Fierce Biotech

---

⚠️ Tolerability: The Other Side of the Story

Here’s where the narrative gets nuanced: although retatrutide exceeded efficacy expectations, the trial also showed tolerability challenges at higher doses.

• About 18.2% of patients on the 12 mg dose dropped out due to adverse events.

• Even at the lower 9 mg dose, 12.2% discontinued treatment—much higher than the 4% seen with placebo.

• Dysesthesia (skin tingling or unusual sensation) occurred in up to 20% at the highest dose—typically mild but notable. Fierce Biotech

This matches patterns seen in other triple-agonist profiles, where more aggressive metabolic action tends to increase GI and sensory side effects compared to dual or mono-agonists. Swolverine

---

🧠 Dr. Simpson’s Take

We are beyond Ozempic vs. Wegovy debates. We are now fully in an era where mechanism matters, not just marketing. Retatrutide’s performance underscores that:

1. Metabolic regulation is not linear.
   Targeting multiple hormonal pathways can yield slightly greater weight loss than dual agonists—but at the cost of a slightly rougher tolerability profile. Reuters

2. GI side effects and discontinuation rates are not trivial.
   Unlike early expectations that this would simply be “Zepbound 2.0,” the real world of tolerability is more complex.

3. Obesity is a biology-first disease, not a character flaw.
   Drugs like retatrutide don’t just nudge appetite—they reprogram energy balance and pain perception. That’s fundamentally incompatible with simplistic moral explanations.

But the burden of stigma persists. Even within medical families and science-friendly social circles, biases persist that belie the biology and echo cultural shame. This disconnect is tragic—and exactly why accurate science communication matters.

---

🔒 Paid Section: Retatrutide vs. Zepbound — Mechanistic Clarity

Paid subscribers, let’s dig deeper into why retatrutide and Zepbound are not just different drugs—they represent different metabolic philosophies.