When it comes to losing weight, pills and injections aren’t just trendy-they’re changing how doctors treat obesity. Two big groups of medications are now at the center of this shift: GLP-1 agonists like Wegovy and Zepbound, and older drugs like orlistat and phentermine. The difference isn’t just in how they work-it’s in how much weight you can lose, how much it costs, and whether you can stick with them long term.
How GLP-1 Agonists Actually Work
GLP-1 agonists mimic a natural hormone your body makes after eating. This hormone, called glucagon-like peptide-1, tells your brain you’re full and slows down how fast your stomach empties. That means you eat less, feel satisfied longer, and your blood sugar stays steadier. These drugs weren’t even made for weight loss at first-they were designed for type 2 diabetes. But doctors noticed patients were losing weight. A lot of it.
Wegovy (semaglutide) and Zepbound (tirzepatide) are the heavy hitters today. Wegovy is a once-weekly shot at 2.4 mg. Zepbound, newer and stronger, is also weekly but works on two hormones instead of one-GLP-1 and GIP. That dual action is why some people lose up to 21% of their body weight in a year. Saxenda (liraglutide) is another GLP-1 drug, but it’s daily and less powerful. Most people lose about 6-8% on Saxenda, compared to 15% or more on Wegovy or Zepbound.
What the Older Drugs Do (and Don’t Do)
Before GLP-1s, the main options were orlistat, phentermine, Qsymia, and Contrave. These have been around for 10 to 20 years. They work differently.
Orlistat (Alli, Xenical) blocks fat from being absorbed in your gut. The fat just passes through you. It’s not magic-it only works if you eat fat. If you skip the fries, you lose almost nothing. Most people lose 5-10% of their weight on it, but many quit because of oily stools and embarrassing side effects.
Phentermine is a stimulant. It suppresses appetite like old-school diet pills. It’s cheap-sometimes under $50 a month-but it’s only approved for short-term use. Qsymia combines phentermine with topiramate (an anti-seizure drug), which adds brain-based appetite control. It can help people lose up to 10%, but it can cause tingling, dry mouth, and mood changes. Contrave pairs naltrexone (used for addiction) with bupropion (an antidepressant) to target the brain’s reward system. It helps with cravings, but results are modest: around 5-8% weight loss on average.
The Real-World Weight Loss Numbers
Clinical trials make GLP-1s look amazing. But trials are controlled. Real life? It’s messier.
In studies, Wegovy users lost about 15% of their body weight. Zepbound hit nearly 21%. That’s 30-50 pounds for someone who weighs 250. But a 2024 study from NYU Langone followed real patients for a year. Only 4.7% lost weight after six months. After a full year? Just 7%. Why the drop? Many stopped taking the drug.
Older drugs aren’t much better in practice. People on orlistat often quit because of digestive chaos. Those on Qsymia report brain fog or anxiety. Contrave doesn’t deliver the punch people expect. The truth? Most people don’t lose more than 10% with any of these-unless they’re on a GLP-1 agonist and stick with it.
Cost: The Biggest Hurdle
Wegovy and Zepbound cost $1,000 to $1,400 a month without insurance. That’s $12,000 a year. Most insurance plans won’t cover them unless you have type 2 diabetes or a BMI over 40. Even then, you might need to try other drugs first, or prove you’ve tried diet and exercise.
Compare that to phentermine: $10-$50 a month. Orlistat: $40-$80. Qsymia and Contrave are pricier, around $100-$150, but still a fraction of GLP-1 costs. Many people can’t afford the newer drugs. A 2024 poll found 62% of people using GLP-1s struggled to pay for them. Even with manufacturer coupons, savings cap out at $500-$1,000 a year-far from enough.
Side Effects: Not Just Nausea
GLP-1s don’t just make you feel full. They make your stomach slow down. That’s good for weight loss. Bad for your digestion.
Nausea hits 20-50% of users, especially when starting or increasing the dose. Vomiting, diarrhea, constipation-common. Some people develop gastroparesis, where the stomach doesn’t empty at all. That’s serious. One Reddit user described feeling like their stomach was “stuck.” Others had to go to the ER.
Older drugs have side effects too. Orlistat = oily leaks. Phentermine = insomnia, high blood pressure, jitteriness. Qsymia = tingling, memory issues. Contrave = headaches, dry mouth. But they’re usually less intense. And they’re oral. No needles.
Who Wins? Who Loses?
GLP-1 agonists win on power. If you need to lose 20+ pounds and can handle the cost and side effects, they’re the most effective option we have right now. They’re especially helpful if you have diabetes-because they lower blood sugar too.
But they’re not for everyone. If you’re needle-averse, they’re a hard sell. If you’re on a tight budget, they’re out of reach. If you can’t tolerate nausea, you’ll quit. And if you stop taking them? Studies show 50-100% of the weight comes back within a year.
Older drugs? They’re weaker, but cheaper, easier to take, and better covered by insurance. If you only need to lose 10-15 pounds, or you’re testing the waters, they’re a reasonable start. Some people use them long-term without major issues.
What About Surgery?
Some people think GLP-1s are replacing surgery. They’re not.
A 2024 study tracked over 50,000 people. Those who had bariatric surgery lost 24% of their body weight after two years. GLP-1 users? 4.7% after six months. Surgery isn’t perfect-it’s invasive, carries risks, and requires lifelong changes. But it lasts. GLP-1s? You need them every week, forever.
And here’s something surprising: Johns Hopkins found one in seven people who had bariatric surgery now take GLP-1 drugs afterward. Why? Because they lost weight but plateaued. Or they gained some back. The drugs help them hold on.
What’s Next?
More drugs are coming. Retatrutide, a triple-agonist targeting GLP-1, GIP, and glucagon, showed 24% weight loss in early trials. MariTide, a new antibody from Amgen, is in Phase 3 testing and looks promising too.
But the big question isn’t about new drugs. It’s about access. Right now, only 28% of commercial insurance plans cover GLP-1s for weight loss without strict rules. As demand grows, insurers are pushing back. Meanwhile, shortages happened in 2023-2024. People waited months just to get a prescription.
And when semaglutide’s patents expire around 2030, generics will come. Prices will drop. That’s when these drugs might finally become mainstream-not because they’re better, but because they’re affordable.
What Should You Do?
Don’t pick a drug because it’s trendy. Pick one that fits your life.
- If you need major weight loss, can afford it, and don’t mind shots-GLP-1s are your best shot.
- If you want something cheap, easy, and low-risk-start with orlistat or phentermine.
- If you have diabetes-GLP-1s give you two benefits at once.
- If you’ve tried everything and still struggle-talk to a specialist about surgery.
And don’t forget: no pill or injection replaces movement, sleep, and food quality. These drugs help you eat less. But they don’t make you healthy. You still have to do the work.
Are GLP-1 agonists better than older weight loss drugs?
Yes, in terms of weight loss. GLP-1 agonists like Wegovy and Zepbound typically lead to 15-21% body weight loss in clinical trials, while older drugs like orlistat, Qsymia, and Contrave usually result in 5-10%. GLP-1s also improve blood sugar and heart health, which older drugs don’t consistently do.
Why are GLP-1 drugs so expensive?
They’re new, patented, and in high demand. Manufacturing biologic drugs like semaglutide is complex and costly. Insurance coverage is limited, especially for weight loss (not diabetes). Without insurance, monthly costs range from $1,000 to $1,400. Even with coupons, savings are capped, leaving many patients paying thousands per year.
Do GLP-1 agonists cause serious side effects?
Common side effects include nausea, vomiting, diarrhea, and constipation, affecting 20-50% of users, especially during dose increases. Rare but serious risks include gallbladder disease, pancreatitis, and gastroparesis. Most side effects improve over time with slow dose escalation, but some people discontinue use due to intolerance.
Can you take GLP-1 drugs long-term?
They’re approved for long-term use, but many people stop within a year. Studies show up to 70% discontinue due to cost, side effects, or lack of results. Weight often returns after stopping, so long-term use may be needed to maintain loss. They’re not a cure-they’re a tool that works only while you’re taking them.
Is there a cheaper alternative to Wegovy or Zepbound?
Yes. Older drugs like orlistat, phentermine, or Qsymia cost $10-$150 per month and are more likely to be covered by insurance. Generic versions of some are available. Some people use these as a stepping stone or for maintenance after stopping GLP-1s. Lifestyle changes-diet, sleep, activity-are always the foundation, regardless of medication.
Should I consider weight loss surgery instead?
For people with severe obesity (BMI ≥40 or ≥35 with health issues), surgery remains the most effective and durable option. Studies show 24% weight loss after two years with surgery versus under 10% with medication alone. Surgery requires commitment and has risks, but it often leads to lasting results without ongoing medication. GLP-1s are not a replacement-they’re an alternative or an add-on.