Hunger Games: Why Diets Fail and Weight Loss Medicines Succeed

After a century of futility, the seemingly impenetrable mystery of weight loss is nearly solved. Until late 2022, most of us were taught that the weight loss journey was paved with willpower. Our Sisyphean task was to create a caloric deficit through diet and exercise and maintain it indefinitely through deliberate effort, food, and activity tracking, and enduring lifestyle changes. For the minority, this formula succeeded.¹ Yet most people found that weight loss was a revolving door: No matter the method or the motivation, their weight eventually returned to roughly the same starting point.²

Then something unexpected happened. Following decades of clinical trials yielding ineffective or even dangerous weight loss medicines,³ a new class of injectable medicines called GLP-1 agonists (GLP=glucagon-like peptide) arrived in 2022-2023.⁴ Not only did the average GLP-1 user experience weight loss far surpassing that usually achieved through lifestyle changes alone, their weight loss generally came with minimal conscious effort. For the first time, people were suddenly achieving clinically significant weight loss without tracking calories, practicing specific diets, or willpowering themselves through high-volume exercise routines. The weight loss journey, for millions, had transformed from an uphill slog to a stroll in the park.

The purpose of this post is to explain this weight loss paradigm change, including how it benefits GLP-1 users and non-users alike. The greatest breakthrough from the GLP-1 medicine era was arguably not the novel psychopharmacology. It was shattering the illusion that weight loss was ever about calorie counting, exercise, or controversial diets. Weight loss, instead, was always about controlling hunger.⁵

Turns out that weight loss was a real-life “Hunger Games.” GLP-1 medicines simply offered us a reliable strategy for finally winning the game.

Winning the Hunger Games

To understand the remarkable effectiveness of bariatric surgery and GLP-1 medicines compared to traditional diet and exercise programs for weight loss, you must understand hunger. Surprisingly to many people, the human body doesn’t possess an internal calorie detector. Your body doesn’t know if you’ve eaten 500 calories or 5,000. Instead, our body evolved to rely on biological proxy systems that, until the recent era of ultra-processed food, functioned extraordinarily well to regulate our weight and appetite across times of feast and famine. These systems include:

1. Stretch detectors in the stomach to register food volume.⁶
2. Appetite hormones such as leptin, insulin, and GLP-1 that partly regulate hunger and satiety.⁷
3. Nutrient sensors in our gastrointestinal tract (GI) that alert the brain to essential nutrients such as proteins, fatty acids, and micronutrients (the complexity of these nutrient sensors is a reason that the human stomach/GI tract has more neurons than the entire brain of many other animals).⁸
4. Palatability detectors in the mouth and brain (e.g., taste buds, brain reward pathways) to help us identify foods that are safe and nutritious.⁹

Consider the above mechanisms in understanding why many diets and exercise programs fail for long-term weight loss.

• Diets are generally low in food volume (failing to activate satiety through stretch receptors).
• Diets tend to be low in nutrients (failing to stimulate nutrient sensors) and often low in palatability.
• And, if too low calorie or too high in exercise volume, many diets and exercise programs activate leptin-signaling pathways that drive compensatory increases in appetite and reduced metabolic activity for many—but not all—people (i.e., lowering energy expenditure).¹⁰

Increased hunger is the predictable result. And if hunger is a horse, weight gain is the wagon it pulls closely behind.

The modern era of ultra-processed food consumption also appears to have driven dramatic rises in obesity and obesity-related health condition rates (e.g., diabetes, liver disease, many forms of cancer) by bypassing the above human satiety mechanisms. For instance:

• Ultra-processed foods frequently contain large amounts of energy (calories) in a size-condensed, low-nutrient, and highly palatable form. An ultra-processed diet is a near-perfect formula for producing fat gain, increased hunger, and frequent emotional cravings (i.e., psychological hunger) in humans due to the way it uniquely hijacks our brain and GI systems.
• Alternatively, a nutrition plan consisting of high fiber and high protein from nutrient-dense whole foods is the single best eating strategy for achieving and maintaining a healthy weight.¹¹ Ideally, this nutrient plan is coupled with a moderate exercise routine that mitigates the compensatory metabolic responses often induced by high-volume exercise programs.

Through precisely the same hunger mechanisms through which diets generally fail, bariatric surgery and GLP-1 medicine succeed.

1. As a hunger control strategy, bariatric surgery is a blunt force instrument. Bariatric procedures directly modify the stomach and—in the case of gastric bypass surgery—the intestinal tract. The result is a long-term or even permanent reduction in hunger through improved stretch detector mechanisms (far less food is required post-surgery to trigger them) and increased function of appetite hormones.
2. If bariatric surgery is a sledgehammer approach to controlling hunger, GLP-1 medicines are a scalpel. First-generation (e.g., Wegovy), second-generation (e.g., Zepbound), and approaching third-generation (e.g., retatrutide) selectively enhance the function of specific appetite hormones and appear to modify palatability and food reward mechanisms. The result is reductions in both physical and psychological hunger for most users.

Takeaway

No matter how you approach your goal of healthy weight loss, hunger is likely to be your most formidable opponent. Although the methods by which they control hunger vary, every effective dietary, physical activity, surgical, and medicinal approach to weight loss capitalizes on known human hunger and satiety mechanisms. In contrast, weight loss methods that fail to adequately control hunger through one or more of these mechanisms rarely produce lasting weight loss. All of us seeking long-term healthy weight management can benefit from the revelations yielded by the new GLP-1 medicines in enhancing our results.