Coming world sans fat people, weight loss while maintaining muscle, intertrigo, belly fat fold fungi
Interesting article in today's WSJ Personal Journal about the next generation of weight loss drugs. Are we headed for a world with no fat people?
The short answer is no. While the next generation of weight-loss therapeutics—triple agonists like retatrutide, amylin combinations like CagriSema, and daily oral small-molecule GLP-1s—are closing the gap between pharmaceutical intervention and bariatric surgery, we are nowhere near eradicating obesity.
GoodRx
The transition from early GLP-1/GIP receptor agonists (like semaglutide and tirzepatide) to multi-hormone targeting represents a genuine paradigm shift. However, several systemic, biological, and economic realities prevent a "world without fat people."
Henry Ford Health
The Pharmacological Reality: What Next-Gen Drugs Actually Do
The current pipeline targets multiple metabolic pathways simultaneously—combining GLP-1, GIP, glucagon, and amylin receptors to suppress appetite, slow gastric emptying, and increase energy expenditure.
Henry Ford Health
[ First Gen ] [ Second Gen ] [ Next Gen / Pipeline ]
Semaglutide Tirzepatide Retatrutide / CagriSema
(GLP-1 Mono-agonist) (GLP-1 / GIP Dual) (Triple / Amylin Combos)
┌──────┐ ┌──────┐ ┌──────────┐
Average Weight Loss: │ ~15% │ │ ~20% │ │ 24-26%+ │
└──────┘ └──────┘ └──────────┘
While achieving a 25% average weight loss brings clinical trials close to surgical outcomes, pharmaceutical mechanics present distinct constraints.
Why Obesity Will Not Disappear
1. The Discontinuation & Rebound Effect
These medications treat the chronic regulation of metabolic set-points rather than providing a permanent cure. Clinical data consistently demonstrate that when patients stop taking GLP-1 or multi-agonist regimens, the body's homeostatic mechanisms reassert themselves.
Appetite returns, gastric emptying normalizes, and most patients regain a significant portion of lost weight within 1–2 years.
bworldonline.com
Indefinite, lifelong compliance is required to maintain maximum weight reduction.
2. Economics, Access, and Coverage
At current price points, long-term adherence presents a substantial financial hurdle.
Insurance Friction: Payers and self-insured employers face significant budget impacts, leading many to restrict coverage, institute lifetime benefit caps, or require strict prior authorizations.
Global Health Disparities: While high-income nations grapple with distribution and insurance coverage, lower-to-middle-income regions—where obesity rates are rising rapidly due to ultra-processed food environments—face severe access barriers due to cost and supply chain logistics.
3. GI Intolerance and Side-Effect Ceilings
Higher-potency multi-agonists inevitably push up against human physiological tolerance.
A notable percentage of trial participants discontinue treatment due to persistent gastrointestinal adverse effects, including nausea, severe constipation, vomiting, or gastroparesis risks.
Henry Ford Health
Off-target effects—such as lean muscle tissue loss alongside fat mass loss—require intensive resistance training and dietary management, which not all patients can sustain long-term.
4. Human Heterogeneity and Choice
Non-Responders: Biological variability dictates that a segment of the population experiences minimal weight response even on triple-agonist therapies.
Personal Preference: Many individuals opt out of long-term medical intervention due to personal choice, aversion to side effects, needle hesitancy (though oral options are emerging), or a rejection of body-normative medicalization.
Henry Ford Health
The Broader Environment
Medicalizing obesity addresses individual physiology, but it leaves the obesogenic environment intact. Ultra-processed, hyper-palatable, calorie-dense foods remain cheap and accessible, while built environments often minimize baseline physical activity. Expecting pharmaceuticals alone to eliminate obesity is like relying solely on statins to eliminate heart disease without modifying dietary patterns or lifestyle factors.
The next generation of therapies will significantly alter public health outcomes and reduce cardiovascular and metabolic disease burdens. However, they function as long-term management tools rather than an absolute eradication mechanism.
Polskie Radio
I'm of two minds about reducing human variability, but obesity has psychological and health consequences. Your reasons for answering my question negatively are based on present circumstances. Quality will improve, the muscle loss issue will be worked out, prices will come down.
That is a fair pushback. If we project forward on a long enough horizon—looking past current manufacturing bottlenecks, pricing, and early-stage side effects—the biological and technological arguments shift significantly.
Assuming small molecules drive manufacturing costs down to the level of statins, combination therapies (like GLP-1/myostatin inhibitors) preserve lean muscle mass, and tolerability improves, the barrier transitions from technical capacity to human, structural, and evolutionary dynamics.
Even in a future where a cheap, side-effect-free, highly effective metabolic stabilizer is as common and accessible as a daily multivitamin, several deep-seated forces would still preserve human body variability.
1. The Homeostatic "Defender" Problem
Human biology isn't just passive tissue; it's an actively defended system evolved over millions of years to prevent starvation.
Metabolic Defense: The human brain (specifically the arcuate nucleus in the hypothalamus) treats weight loss as a threat to survival. Even when drugs successfully suppress appetite signals, the body responds by dialing down basal metabolic rate, altering thyroid hormone output, and increasing non-exercise activity fatigue.
The Escalation Barrier: To completely eliminate obesity across an entire population, drugs must permanently override these deeply entrenched evolutionary feedback loops. As pharmacology gets more powerful at silencing these signals, the biological counter-measures become more complex to manage over decades of continuous use.
2. Behavioral Heterogeneity and Human Friction
Even when safe, highly effective medical interventions exist for widespread health conditions, population-level adoption rarely reaches 100%.
Compliance and Fatigue: Public health history shows that long-term adherence to prophylactic or lifestyle-managing medications declines significantly over time, even when free and life-saving (e.g., blood pressure medication, statins, maintenance therapies).
The "Good Enough" Plateau: Many individuals might use future therapies to reach a state of improved mobility, blood sugar control, or comfort, without pursuing a standardized body fat percentage. Human goals for health and appearance vary widely.
3. Culture, Identity, and Choice
Your mention of "reducing human variability" hits on the core ethical and cultural philosophical question.
Variability as Normalcy: Body diversity is bound up in culture, identity, age, and individual priority. A world where fatness is universally framed as a target for pharmaceutical elimination assumes a level of social homogenization that history suggests humans resist.
Autonomy: Unless intervention becomes mandatory—an extreme dystopia—a non-trivial portion of any population will simply choose not to medicate, preferring their natural baseline, avoiding lifelong pharma reliance, or prioritizing other personal values over physiological optimization.
4. The Upstream Environment
Pharmaceuticals operate at the individual end of the spectrum, while the modern environment operates at the population end.
Ultra-processed, hyper-palatable foods are designed to exploit human neural reward pathways.
Modern built environments minimize mandatory physical movement.
If the baseline environment continuously pushes human biology toward caloric surplus, drugs are acting as an active dam against a permanent, rising river. The moment the dam leaks—via missed doses, life disruptions, or biological adaptation—the environmental pressure reasserts itself.
The Realistic Horizon
A frictionless, high-quality, cheap generation of metabolic drugs will almost certainly transform public health, dramatically lower rates of severe obesity, and reduce the burden of type 2 diabetes, cardiovascular disease, and joint pathology.
However, rather than creating a uniform world with no fat people, it is more likely to transform obesity from a rampant, systemic public health epidemic into a manageable, widely varied human trait—one shaped far more by personal choice, biological spectrums, and individual lifestyle priorities than by unavoidable metabolic destiny.
Yeah, I've always been big and burly, and it has advantages and disadvantages.
That live-in experience of carrying a larger, sturdier frame gets straight to the heart of why a totally uniform, low-fat world isn't particularly desirable—let alone likely.
There’s an undeniable trade-off to naturally having more mass and presence:
The Functional Upsides: Raw physical leverage, thermal tolerance in cooler weather, natural strength without needing to spend half your life in a gym, and a quiet, passive physical presence that changes how spaces—and people—react to you.
The Practical Downsides: The mundane mechanics of a world built for the medium-small average. Standard seats, doorways, legroom, and off-the-rack clothing rarely account for broad shoulders or thick frames. Plus, as the decades accumulate, carrying more mass places a higher, constant baseline tax on joints and the cardiovascular system, regardless of how much of that frame is muscle versus fat.
This is precisely why a purely pharmaceutical view of body composition falls short. High-potency GLP-1s and multi-agonists treat weight purely as a uniform health risk factor to be dialed down on a chart. But human bodies aren't just clinical metrics; they are physical vehicles shaped by structure, stature, and personal utility.
A frame that is naturally "big and burly" comes with a built-in baseline of bone density, muscle distribution, and physical leverage that a daily pill or injection isn't meant to—and shouldn't—erase.
Want to look into how multi-agonists affect lean muscle mass versus fat loss?
Yes
I carry more belly weight than is advisable, proved by the presence of a belly fat fold where fungi have to be carefully controlled. I also suffer from balance problems that mandates a cane or grab holds or someone who's shoulder I can grasp. Muscle loss would make that worse, so I will wait.
That is a completely grounded, pragmatic decision based on your actual, daily physical reality.
When media or clinical trials talk about weight loss purely in terms of pounds on a scale, they often miss the functional trade-offs you are managing every day:
The Balance & Stability Factor: Balance issues change the calculus entirely. To use a cane safely, manage grabs, or steady yourself against someone's shoulder, you need significant upper-body, core, and leg strength. Because 20% to 40% of the weight lost on current GLP-1 medications can come from lean muscle mass rather than fat, rapid weight loss right now could directly compromise the very strength and joint feedback you rely on to stay upright and mobile.
Skin Fold / Intertrigo Challenges: The paradox of rapid weight loss when you carry a distinct belly fold is that losing subcutaneous fat quickly can actually worsen skin overlap in the short term, leaving loose skin folds that are even harder to keep dry and clean from fungal overgrowth (intertrigo).
Waiting for the science to catch up to your specific needs makes a lot of sense. The drug pipeline is actively working on two areas that directly address your situation:
Muscle-Preserving Combinations: Therapies pairing GLP-1s with myostatin inhibitors or bimagrumab are currently in trials specifically to protect or even build lean muscle mass while targeting fat.
Targeted Visceral Fat Loss: Future formulations aim to prioritize visceral/belly fat over lean structural tissue, reducing abdominal volume without stripping away functional strength.
Until those treatments are proven, safe, and tailored to preserve physical stability, protecting your muscle and balance is the priority. Managing skin fold hygiene meticulously while keeping your functional strength intact is a far better strategy than risking a fall for the sake of a lower number on the scale.
Thank the heavens for corn starch.
It is a modest, absolute miracle of daily survival. Simple, incredibly effective, cheap, and entirely silent about its work.
In hot or humid climates, keep-dry powders like cornstarch do the heavy lifting that no expensive medical cream can replicate: absorbing moisture before it fuels an environment where fungi and bacteria thrive, reducing friction between skin surfaces, and keeping things comfortable enough to move without chafing.
Sometimes the most reliable tools in a physical life aren't high-tech pharmaceuticals at all—just a basic, dependable staple that keeps daily maintenance simple and manageable.
And it has no scent.
That unscented simplicity is a huge part of its quiet genius.
So many modern hygiene products, anti-chafing creams, and powders come heavily perfumed with artificial floral or herbal scents that mix horribly with sweat, irritate sensitive, inflamed skin, and make it obvious to anyone nearby what you're trying to manage.
Unscented cornstarch just does its job without any drama, artificial additives, or perfumed masking agents. It keeps the skin dry, neutral, and calm, letting you go about your day without smelling like a cosmetic aisle.
Gemini is AI and can make mistakes.
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