The quest for effective weight loss solutions has led to a surge in the popularity of weight loss pills, particularly glucagon-like peptide-1 (GLP-1) receptor agonists. Drugs like Ozempic, initially intended for diabetes treatment, and Wegovy and Zepbound, specifically marketed for obesity, have gained considerable attention. While these medications offer hope for many, it's crucial to understand their effectiveness, potential side effects, and how they fit into a comprehensive weight management plan.
The Allure and History of Weight Loss Medications
The demand for weight loss drugs is overwhelming. The history of weight loss medication is littered with drugs that seemed like impressive, easy solutions - at first. Amphetamines were once widely prescribed for weight loss, until they were linked to high blood pressure, heart complications, anxiety, and aggression. Fen-phen, a combination of fenfluramine and phentermine, was a popular diet drug in the ’90s, but it’s far from the only pharmaceutical failure.
How GLP-1 Drugs Work
The latest treatments might be the solution some patients have been hoping for. GLP-1 drugs work by mimicking a hormone called glucagon-like peptide-1 (GLP-1), which curbs hunger. GLP-1 also slows down the movement of food from the stomach to the small intestine - hence a feeling of fullness - and increases insulin production, lowering blood sugar. The gist? GLP-1 drugs make you eat less. Over time, obese patients lose roughly 12% of their body weight on Wegovy (semaglutide) and about 18% on Zepbound (tirzepatide, which targets GLP-1 and another gut hormone, GIP.) Recent studies have shown that semaglutide also helps people with obesity lower their high blood pressure and reduce their odds of heart attacks or strokes. Early evidence suggests the drugs might also improve depression and substance abuse disorders.
Potential Side Effects and Risks
The potential side effects of GLP-1 drugs are no fun: nausea, vomiting, fatigue, diarrhea, constipation. For others, GLP-1 agonists can slow digestion to a problematic degree. Patients have sued the drugmakers after developing dangerous conditions, such as stomach paralysis and bowel obstructions. The stomach contents are retained sometimes for days on GLP-1s. People facing surgery have fasted for 24 hours so they can safely get anesthesia. It might have helped with their diabetes and weight loss.
Access and Affordability
The soaring demand for GLP-1s has created shortages across the country. In response, semaglutide and tirzepatide were added to the FDA Drug Shortages Database, allowing compounding pharmacies to produce generic versions. In turn, telehealth companies began selling the drugs at prices far lower than the average $1,300 per month paid for brand-name GLP-1s.
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Shortages aside, many insurers still won’t pay for GLP-1 agonists unless the patient has been diagnosed with diabetes or cardiovascular disease. A 2003 law currently prohibits Medicare from covering drugs for weight loss alone. Meanwhile, states get to decide whether to cover the drugs under Medicaid. The net result? A lot of people struggling with obesity can’t afford the most effective treatment.
The Importance of a Holistic Approach
To be clear, eating a lot less does drop the numbers on the scale. But exercise is still important - for your heart, bones, brain, and more. And the nutritional quality of your food matters, not just the quantity. People taking them have fewer cravings. Legislative efforts to expand insurance coverage for GLP-1 medications are already underway.
Psychological and Social Considerations
Online, speculation runs wild on what the rise of GLP-1s will mean for American culture and, in turn, our mental health. Are we devolving to a ’90s-era obsession with thinness? Social pressure to look thin never really went away.
You can see some people mourning their previous selves. A patient told me, ‘People used to be so mean in public.’ Now, they’ve lost weight and society is treating them better.
Long-Term Use and Sustainability
Once you start taking GLP-1s, the drugmakers suggest you stay on them. People who go off the drugs eventually regain much of their lost weight. Indulgence is, for better or worse, how many people relax, celebrate, socialize. The factors fueling excess weight are complex: social, environmental, genetic. But big picture, biologically, humans evolved in scarcity. We live in a food environment that is constantly pressuring people to make indulgent decisions.
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Alternatives and Emerging Treatments
A groundbreaking new obesity treatment in pill form is showing exciting early promise. In a first-of-its-kind human study, researchers tested SYNT-101, a once-daily oral medication designed to safely and effectively shift nutrient absorption to the lower intestine. The early results are encouraging. “We believe that SYNT-101 will provide a convenient, more sustainable oral alternative and/or complement to systemic therapies such as GLP-1 drugs. In addition, this “duodenal nutrient exclusion” effect improves satiety and metabolic regulation, and has been shown to better preserve lean muscle mass compared to GLP-1 drugs.
GLP-1s After Bariatric Surgery
Bariatric surgery is usually effective on its own for weight loss, but an increasing proportion of patients who undergo bariatric surgery start taking one of the new glucagon-like 1 peptide receptor agonist (GLP-1) weight-loss drugs in the years after their surgery.
Individuals with lower post-operative weight loss were more likely to use GLP-1. The analysis showed that the rate of post-surgery GLP-1 use increased during the 2015-2025 study window as more powerful GLP-1 drugs such as semaglutide and tirzepatide became available.
Comparing GLP-1s to Bariatric Surgery
Researchers from NYU Langone Health and NYC Health + Hospitals discovered patients who had one of the bariatric procedures lost an average 58 pounds after two years compared to 12 pounds for patients who received a GLP-1 prescription for at least six months (24% total weight loss vs. 4.7%).
The Role of Pharmacotherapy Post-Bariatric Surgery
Results of this systematic review suggest pharmacotherapy may be an effective tool as an adjunct to diet and physical activity to support weight loss in post-bariatric surgery patients. Trials for weight loss medications often exclude patients who have had bariatric surgery. As such, weight loss pharmaceuticals are not approved for use in this patient population.
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Prescription Weight-Loss Drugs
Prescription drugs are medicines that a health care provider prescribes for you. Your health care provider may suggest a weight-loss drug for you in some cases. Before choosing a medicine for you, your health care provider thinks about your history and health challenges. Mild side effects, such as nausea, constipation and diarrhea, are common. They may lessen over time. Rarely, serious side effects can happen. Many people gain back some of the weight they lost when they stop taking weight-loss drugs.
Most prescription weight-loss drugs work by making you feel less hungry or fuller. Some do both. The exception is orlistat.
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