When did obesity become a drug deficiency?

What changed was almost everything

Today, people live in a very different world than past generations. Food is everywhere, all the time. Much of it is designed to be convenient, tasty, long-lasting, quick to eat, and easy to buy again. Foods that once took time to prepare can now be eaten in seconds. Drinks can add a lot of calories without making us feel full. Portion sizes have grown, people move less, jobs are more sedentary, transportation often means less walking, and entertainment usually means sitting. No single food or habit explains obesity, but the environment that shapes our eating and activity has changed a lot.

A key experiment by Hall and his team at the National Institutes of Health showed this clearly. In a controlled study, people ate either ultra-processed or unprocessed diets, matched for calories, nutrients, sugar, salt, and fiber. They could eat as much or as little as they wanted. On an ultra-processed diet, people ate about 500 more calories a day and gained weight. On the unprocessed diet, they lost weight.[9] No one told them to eat more or took away their willpower. Just changing the food environment changed how much they ate.

Physical activity has also dropped a lot. A large study of over 5 million people found that not getting enough exercise became more common worldwide from 2000 to 2022, and by 2022, almost a third of adults weren't active enough.[10] Sleep is important too, even though it's often overlooked. Research shows that not getting enough sleep raises the risk of obesity.[11] All these factors, along with stress, income, medications, food access, work hours, city design, and more, combine in ways that can't be fixed by simply telling people to eat less and move more.

Scientists are also looking at environmental chemicals that might affect metabolism and hormones. The idea of "obesogens" is still new and shouldn't be seen as the only reason for the obesity epidemic. Still, studies suggest that some environmental exposures could affect how our bodies store fat, use energy, or regulate appetite in ways that make weight gain more likely.[12] The right approach is to keep studying these possibilities, especially since the rise in obesity is so widespread.

The most defensible conclusion is therefore also the least sensational: obesity probably does not have one cause. Food changed. Physical activity changed. Sleep changed. Work changed. Transportation changed. Stress changed. Medications changed. Chemical exposures changed. Marketing changed. Portion sizes changed. The economics of food changed. The built environment changed. Human beings then responded biologically to those changes.

The mystery is not that metabolism responded to a dramatically altered environment. The mystery is why medicine became so comfortable treating that response without demonstrating comparable urgency about the environment that produced it.

Then came the drugs that actually worked

Obesity medicine has a long and sometimes uncomfortable pharmacological history. Earlier drugs frequently produced modest weight loss, troublesome adverse effects, or both. Several were eventually withdrawn because their risks became unacceptable. Against that background, modern incretin-based therapies represented a genuine therapeutic breakthrough. In the STEP 1 trial, adults with overweight or obesity who received once-weekly semaglutide 2.4 mg lost an average of 14.9 percent of their baseline body weight over 68 weeks, compared with 2.4 percent among those receiving placebo, with both groups receiving lifestyle intervention.[3] For nonsurgical obesity treatment, this was an extraordinary result.

Tirzepatide moved the numbers even further. In SURMOUNT-1, 2,539 adults with obesity or overweight and at least one weight-related complication, but without diabetes, were randomized to tirzepatide or placebo. At 72 weeks, average weight reductions were 15.0 percent, 19.5 percent, and 20.9 percent with the 5 mg, 10 mg, and 15 mg doses, respectively, compared with 3.1 percent with placebo.[4] Weight reductions exceeding 20 percent begin to approach territory historically associated with bariatric procedures rather than medication. For patients who have struggled unsuccessfully with obesity for years, it is easy to understand why these drugs can feel revolutionary.

More importantly, the story extends beyond the scale. In SELECT, more than 17,000 adults with preexisting cardiovascular disease and overweight or obesity, but without diabetes, were randomized to semaglutide or placebo. Major cardiovascular events occurred in 6.5 percent of patients receiving semaglutide and 8.0 percent receiving placebo, corresponding to a hazard ratio of 0.80.[5] Subsequent analysis also demonstrated a lower incidence of a prespecified composite kidney endpoint among patients receiving semaglutide.[13] Tirzepatide has produced substantial reductions in apnea-hypopnea index among patients with obesity and moderate-to-severe obstructive sleep apnea.[6] These findings make it impossible to dismiss the GLP-1 era as mere pharmaceutical vanity medicine.

Physicians should welcome effective therapies. A patient with severe obesity, cardiovascular disease, diabetes, sleep apnea, impaired mobility, or other obesity-related complications should not be denied a beneficial treatment because society has failed to solve the larger causes of obesity. We treat the patient who exists today, not the healthier society we wish existed. The mistake would be turning that entirely reasonable clinical principle into permission to stop asking the larger question.

What happens when the injection stops?

Perhaps the most revealing aspect of GLP-1 therapy appears when treatment ends. In the STEP 1 extension, participants who discontinued semaglutide regained approximately two-thirds of their previous weight loss during the following year, while many cardiometabolic improvements moved back toward baseline.[14] SURMOUNT-4 demonstrated a similar phenomenon with tirzepatide. After an initial 36-week period during which participants lost an average of 20.9 percent of their body weight, those randomized to discontinue tirzepatide and receive placebo regained substantial weight, whereas those who continued therapy maintained and further increased their weight reduction.[15]

The conventional interpretation is straightforward: obesity is a chronic relapsing disease, and chronic diseases frequently require chronic treatment. This argument has considerable logic. Blood pressure often rises when antihypertensive medications are stopped. LDL cholesterol generally rises after discontinuation of lipid-lowering therapy. Nobody claims that the recurrence of hypertension proves that antihypertensive drugs failed.