The Food and Drug Administration (FDA) has approved several medications for weight loss, each with varying degrees of effectiveness in helping individuals achieve their weight loss goals. These drugs, often administered as weekly injections, function by augmenting insulin production to regulate blood sugar levels and slowing gastric emptying, which ultimately suppresses appetite. This article delves into the efficacy of these weight loss drugs, comparing their mechanisms, clinical trial results, and potential benefits.
Zepbound vs. Wegovy: A Comparative Analysis
Recent data released by Eli Lilly, the maker of Zepbound, has revealed that Zepbound, a drug with the active ingredient tirzepatide, is more effective than Wegovy, a drug with the active ingredient semaglutide, in promoting weight loss.
In a study involving 751 participants with obesity or overweight individuals with related medical conditions, Zepbound demonstrated superior weight loss results. After 72 weeks of treatment, participants taking Zepbound experienced a 20% reduction in body weight, compared to just under 14% for those on Wegovy. This translates to an average weight loss of approximately 50 pounds for Zepbound users versus 33 pounds for Wegovy users during the trial period.
Dr. Louis Aronne, a principal investigator in the clinical trial, suggests that the success of tirzepatide-based drugs like Zepbound is attributable to their dual-hormone targeting mechanism. Tirzepatide targets both the GLP-1 and GIP receptor agonists, while semaglutide, found in Wegovy and Ozempic, mimics only the GLP-1 receptor agonist.
Aronne noted that the body naturally releases seven to eight hormones when food is consumed to provide a sense of fullness. The fact that tirzepatide mimics the effects of two hormones produces a "greater effect" when it comes to weight loss, he explained.
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The Role of GLP-1 Receptor Agonists
Semaglutide, the active ingredient in Wegovy and Ozempic, mimics the GLP-1 receptor agonist, a hormone that influences various bodily functions, including brain activity, muscle function, and pancreatic, stomach, and liver activity. These drugs work by helping the pancreas increase the production of insulin to move sugar from the blood into body tissues. They also slow down the movement of food through the stomach and curb appetite, thereby causing weight loss.
Novo Nordisk, the maker of Wegovy and Ozempic, asserts its confidence in semaglutide, highlighting that Wegovy is the only obesity medicine proven to reduce the risk of major cardiovascular events, such as death, heart attack, or stroke, in adults with known heart disease and obesity or overweight.
Mounjaro and Ozempic: Another Comparison
Another study published in July revealed that Mounjaro, also containing tirzepatide, was more effective for weight loss than Ozempic, which contains semaglutide.
Both Ozempic and Mounjaro are FDA-approved for treating Type 2 diabetes, but doctors sometimes prescribe them "off-label" for weight loss, as permitted by the FDA.
Individual Responses and the Importance of Variety
While significant weight loss might be a primary goal for some individuals, it may not be for others. This is why it's important that multiple drugs are available, according to Aronne.
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"We now have more than two years of experience using these medicines for weight loss, and what we're seeing is that, in some cases, one drug is better, it has fewer side effects, and perhaps greater efficacy than the other," Aronne said. "And so like many areas of medicine, it depends on the patient."
He continued, "One thing you have to remember is everybody doesn't need the most weight loss. There are people who will benefit from greater weight loss, but not everyone needs the most weight loss."
Additional Benefits: Reduced Alcohol Consumption
Emerging research suggests that GLP-1 medications like semaglutide and liraglutide may have additional benefits, including reducing alcohol consumption. A study presented at the 32nd European Congress on Obesity in Spain found that these drugs helped heavy drinkers cut alcohol consumption by nearly 70%.
The study, which followed 262 adults prescribed GLP-1 medications for weight loss, found that heavy drinkers experienced the most significant reduction in alcohol consumption. Researchers hypothesize that GLP-1 drugs may affect brain chemicals tied to pleasure and fullness, though more research is needed to fully understand the exact mechanism.
The Importance of Lifestyle Modifications
Medical specialists emphasize that weight loss medication should be complemented by lifestyle modifications, including regular cardio and strength training, and a diet rich in proteins and low in processed foods and added sugars.
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Side Effects and Considerations
The most commonly reported side effects of weight loss medications are nausea and constipation, although gallbladder and pancreatic disease have also been reported.
The Future of Weight Loss Medications: Oral Options
Eli Lilly is developing an oral, daily GLP-1 pill called orforglipron, which has shown promising weight loss results in Phase 3 trials. According to Eli Lilly, adults in the Phase 3 trials all lost weight with orforglipron and on the highest dose of 36 mg of orforglipron, the trial participants lost about 27 pounds over the course of 72 weeks or about 12% of their body weight, which is meaningful but not quite as high as some injectables. The trial participants also showed cardiovascular improvements after taking orforglipron, including lower systolic blood pressure, lower non-HDL cholesterol and lower triglycerides.
Doctors say patients who don't want to use injectable medications may find oral pills easier to stick with. The oral pills can also be a future option for people who wish to transition away from injectables. Medications in pill forms are also cheaper to manufacture, which in theory, would make these drugs cheaper for consumers.
The company plans to submit orforglipron for global regulatory approval by the end of 2025, joining Novo Nordisk, which is also seeking approval for an oral version of its Wegovy semaglutide medication.
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