Welcome back to Peptide Purgatory, where science meets satire and the duodenum gets its moment in the spotlight.
This week, we plunge beneath the taste buds to explore why food starts tasting funny once GLP-1s take over the metabolic orchestra. It turns out that semaglutide and tirzepatide don’t just curb appetite—they may be rewriting the sensory playbook, one receptor at a time.
Taste Buds on Tirzepatide
When your duodenum rewires your cravings
If food has lost its luster since you started your weekly jab of Mounjaro or Ozempic, you’re not imagining it. A new study presented at the European Association for the Study of Diabetes in Vienna found that more than half of GLP-1 RA users reported changes in how things taste—especially sweets and salt. Strangely, those who said flavors got more intense also reported stronger feelings of fullness and less interest in eating.
That’s right: the folks who tasted sugar more sharply were the ones who stopped chasing it. Nature’s little irony.
The Graz research team led by Othmar Moser surveyed 411 adults on semaglutide (Ozempic, Wegovy) or tirzepatide (Mounjaro, Zepbound). About one in five said sweet or salty tastes grew stronger; roughly two-thirds reported reduced appetite and food cravings. Those heightened taste perceptions weren’t linked to more weight loss, but they did correlate with greater satiety—a sign that GLP-1s may be dialing up the sensory signal to help the brain say “enough.”
It’s All in Your Head
Moser’s group believes GLP-1 and GIP receptors in the taste buds, brainstem, and higher cortical regions tweak how food cues are valued, muting the “reward” circuitry that normally drives us to finish the fries. It’s not just a gut hormone doing metabolic housekeeping—it’s running quality control on pleasure itself.
This fits perfectly with the emerging view of the duodenum as command central for appetite. As Hoyt et al. (2024) describe in their deep dive on duodenal mucosal resurfacing, the upper small intestine is a sophisticated nutrient-sensing organ whose enteroendocrine cells release GLP-1, GIP, and CCK to choreograph digestion, insulin release, and hunger. When that mucosal signaling gets warped by decades of high-fat, high-sugar diets, the body’s sense of “enough” fades. GLP-1 RAs, in essence, reboot the same circuitry that duodenal mucosal resurfacing attempts to physically reset.
So when that slice of cake suddenly tastes like a sugar bomb and you’re done after two bites, think of it as neural remodeling in progress. Your duodenum and brain are renegotiating their sensory contract—less dopamine, more discipline.
Of course, Big Pharma won’t say it quite that way. They’d rather show a grinning patient dancing through the supermarket to celebrate freedom from cravings. But the real story isn’t musical—it’s molecular. GLP-1 RAs alter the gut-brain axis so profoundly that even taste becomes part of the therapy.
Whether this recalibration lasts after discontinuation remains anyone’s guess. For now, the best advice is to savor what’s left of your sweet tooth while it still recognizes dessert.
My Week on Mounjaro and Farxiga
Two weeks into Farxiga, I’ve noted some additional weight loss, but no change in my glucose measurements. Although SGLT-2i therapy is directed at forestalling progression of chronic kidney disease, the initial use of this class of drugs was glucose control. So, I was expecting the glucose numbers to improve.
Perhaps the pizza party Friday night had something to do with that…
- Body Weight: 170.6 lbs (77.5 kg) – down 2.2 lbs (1 kg)
- Fasting Avg. Glucose: 109 mg/dL (6.1 mmol/L) – up 1 mg/dL
- Average Glucose (Stelo sensor): unreliable… sensor died prematurely
- Current HbA1c (17 September): 5.5% (37 mmol/mol)
Let’s wrap up this week with a pile of populist bullshit.
Bullshit Corner: The Family That Deals Together
Donald Trump is once again crowing about “cutting drug prices,” and the faithful are lapping it up like warm ivermectin. This week’s spectacle stars Pfizer, cast as the repentant Big Pharma giant signing a “historic deal” to lower prices. Cue the MAGA ticker tape.
Reality check: these concessions aim mostly where Uncle Sam already has leverage—Medicaid and select categories—while Pfizer gets goodies like tariff relief and policy certainty in return. Trump world trumpets “Most Favored Nation” pricing; Pfizer calls it a landmark; investors shrug and carry on. Translation: negotiated optics, limited shock to Pfizer’s bottom line.
And—because every show needs a website—there’s TrumpRx, a government-blessed portal that won’t sell meds itself but will “connect” patients to manufacturer deals at “the lowest prices in America.” New middleman, new logo, same Washington alchemy. Populism as product placement.
Meanwhile, Big Pharma isn’t waiting for White House branding. Eli Lilly’s Lilly Direct has been shipping Zepbound/Mounjaro and other meds straight to patients since last year—sometimes via self-pay channels the company touts as steeply discounted versus list. It isn’t charity; it’s market capture. But it’s real infrastructure, already operating.
Now for the grown-ups: Mark Cuban’s Cost Plus Drugs. Public launch in 2022 (with earlier groundwork), a simple rule—cost + 15% + pharmacy/shipping—and relentless transparency. More importantly, it has delivered meaningful savings on high-cost generics that matter to seriously ill patients (think transplant meds and oncology agents like imatinib that others price in the thousands per month). Cuban’s outfit is also pushing vertical integration, including manufacturing to shore up supply. This is substance, not stagecraft.
Stack the models:
Cuban publishes the math, cuts out bloat, builds supply—even manufacturing—and passes along savings,
especially on costly chronic-disease meds. Serious player.
Lilly Direct lays corporate DTC rails to claw back share from compounders and telehealth mills.
Professional, self-interested—sure—but functioning.
TrumpRx + “deals” deliver splashy announcements, selective discounts, tariff quid pro quos, and a portal that
“connects” you to prices the government blessed. Window dressing with ample room for favoritism.
As a conservative and a cynic, I respect a clean hustle. But let’s not confuse pay-to-play populism with reform. When the cure is a press conference and the family pharmacy rings up the sale, that’s branding, not relief. Cuban’s model makes sick people’s lives cheaper now. Trump’s makes the headlines cheaper today and the fine print expensive tomorrow. Call it what it is: BULLSHIT!
If it looks like a “deal,” sounds like a “deal,” and Wall Street loves the “deal,” check who’s cashing the receipt.
Washington shenanigans aside, if dinner feels more dutiful than delightful, blame your gut’s new management. The same hormone axis that used to scream for cheesecake is now politely declining the bread basket. Whether this rewiring endures after the last injection remains to be seen, but for now, the GLP-1 crowd is discovering that satiety can be as much about circuitry as calories.
Next week, we’ll see what other miracles Big Pharma wants to attribute to its metabolic messiah. Until then, chew thoughtfully—your duodenum is listening.
For an annotated catalog of all my Peptide Purgatory and Mounjaro updates, visit my Mounjaro Update Catalog page.
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