When it comes to losing weight with medication, the landscape has changed dramatically in the last five years. What used to be a field dominated by pills that barely moved the needle-like orlistat or phentermine-is now ruled by powerful injectables that can help people lose a quarter of their body weight. At the center of this shift are GLP-1 agonists: drugs like Wegovy, Zepbound, and Saxenda. But they’re not the only option. Older weight loss medications are still out there, cheaper and easier to take. So which one actually works better? And more importantly, which one makes sense for you?
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. It also helps your pancreas release insulin when blood sugar rises. That’s why these drugs were first developed for type 2 diabetes. But doctors quickly noticed something else: patients lost a lot of weight.
Drugs like semaglutide (Wegovy) and tirzepatide (Zepbound) are given as weekly injections. You start with a tiny dose-like 0.25 mg-and slowly increase over several months. This slow ramp-up helps your body adjust and cuts down on side effects like nausea. By the time you reach the full dose, your appetite drops noticeably. People often say they just don’t feel hungry anymore, even when they used to snack constantly.
And the results? In clinical trials, Wegovy led to an average of 15% body weight loss over a year. Zepbound, which also targets a second hormone (GIP), pushed that number to nearly 21%. That’s not just a few pounds. That’s someone who weighed 220 pounds dropping to 187-or even 174-with medication alone.
What About the Older Drugs?
Before GLP-1 agonists, the main options were pills you took every day. Orlistat (Alli, Xenical) blocks fat from being absorbed in your gut. You end up passing undigested grease in your stool-messy, but effective for some. It typically leads to 5-10% weight loss. Then there’s phentermine-topiramate (Qsymia), a combo pill that suppresses appetite and changes how your brain processes hunger signals. It can get you to 10% weight loss, but it comes with risks like increased heart rate and mood changes.
Naltrexone-bupropion (Contrave) works on brain reward pathways. It’s meant to reduce cravings, especially for sweets. But in real life, most people only lose about 5-8%. And phentermine, the oldest of them all, is a stimulant that’s been around since the 1950s. It works short-term, but tolerance builds fast, and side effects like insomnia and anxiety make it hard to keep taking.
The difference isn’t subtle. GLP-1 agonists don’t just nudge your weight down-they shift your entire relationship with food. Older drugs? They’re like trying to hold back a flood with a bucket.
Cost: The Biggest Hurdle
Here’s the catch: GLP-1 agonists cost a lot. Without insurance, you’re looking at $1,000 to $1,400 a month. That’s more than most people spend on rent or car payments. Even with coupons, savings are capped at $500-$1,000 a year. For many, that’s still out of reach.
Older drugs? Orlistat can cost under $50 a month. Phentermine is often $10-$30. Qsymia and Contrave run $100-$150, but many insurance plans still cover them. GLP-1s? Only 28% of commercial insurance plans cover them for weight loss without strict requirements-like a BMI over 35 and at least one other health condition like high blood pressure or diabetes.
That’s why so many people stop. A 2024 study from NYU Langone found that after six months on a GLP-1 drug, patients lost only 4.7% on average-not the 15% you hear about in trials. Why? Many ran out of money. Others couldn’t handle the nausea. Some just didn’t lose enough to justify the cost.
Side Effects: Nausea, Vomiting, and the Reality of Adjustment
GLP-1 agonists aren’t magic. About half of users experience nausea, especially when starting or increasing the dose. Some get vomiting, diarrhea, or constipation. A few report severe stomach issues that feel like gastroparesis-where food just sits in the stomach. In rare cases, people need medical help.
The trick is patience. Doctors recommend starting low and going slow. It can take 4-5 months to reach the full dose. During that time, anti-nausea meds like ondansetron can help. Eating smaller meals, avoiding greasy food, and staying hydrated also makes a big difference.
Older drugs have side effects too. Orlistat causes oily spotting and urgent bowel movements. Qsymia can cause tingling in hands and feet, dry mouth, and mood swings. Contrave can raise blood pressure. But none of them cause the same level of digestive disruption as GLP-1s. If you can’t tolerate nausea, you won’t stick with it.
Real-World Results vs. Clinical Trials
It’s easy to get excited reading about 20% weight loss in a trial. But trials aren’t real life. In trials, people are closely monitored, given counseling, and have access to support. In real life, most people are left to figure it out on their own.
That’s why real-world data tells a different story. The same NYU Langone study found that after one year, patients on GLP-1 drugs lost only 7% on average. And 70% stopped taking the drug within a year. Why? Cost, side effects, or just not seeing the results they expected.
Compare that to bariatric surgery. In the same study, patients who had gastric bypass lost 24% of their body weight after two years. And they kept it off longer. Surgery isn’t perfect-it’s invasive, risky, and requires lifelong changes. But for people who’ve tried everything else, it often works better than any pill.
Who Benefits Most From GLP-1 Agonists?
These drugs aren’t for everyone. But they’re a game-changer for some:
- People with type 2 diabetes who need to lose weight and control blood sugar at the same time
- Those with a BMI over 30 (or 27 with weight-related health issues) who’ve tried diet and exercise without success
- People who can afford the cost-or have insurance that covers it
- Those willing to deal with injections and side effects for the chance at major weight loss
If you’re looking for a quick fix, or you hate needles, or you can’t pay $1,000 a month, GLP-1s probably aren’t right for you. But if you’ve been struggling for years and want real, lasting change, they might be the best option you’ve ever had.
What’s Coming Next?
The next wave of weight loss drugs is already here. Retatrutide, a triple agonist that targets GLP-1, GIP, and glucagon, showed 24% weight loss in early trials. MariTide, a new antibody from Amgen, is in late-stage testing and looks promising too. These could push weight loss beyond 25%.
But they’ll also be even more expensive. And when semaglutide’s patents expire after 2030, generic versions may drop prices. Until then, access remains limited. For now, GLP-1 agonists are the most powerful tool we have outside of surgery. But they’re not the only tool.
Final Thoughts: It’s Not Either/Or
GLP-1 agonists aren’t replacing older drugs-they’re raising the bar. Some people will do fine on Qsymia or orlistat. Others will need the power of Wegovy or Zepbound. And for many, surgery remains the most effective long-term solution.
The key is matching the tool to the person. If you’re struggling to lose weight and your doctor hasn’t talked to you about GLP-1s, ask. If you’re worried about cost, ask about patient assistance programs. Novo Nordisk and Eli Lilly both have programs that can help cut the price. If you’re scared of needles, talk to your doctor about oral semaglutide (Rybelsus)-it’s not as strong, but it’s a pill.
Weight loss isn’t about finding the best drug. It’s about finding the right one-for your body, your budget, and your life.
Are GLP-1 agonists better than older weight loss drugs?
Yes, in terms of weight loss effectiveness. 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 reduce heart risks, which older drugs don’t. But they’re more expensive and require injections.
How much do GLP-1 weight loss drugs cost?
Without insurance, GLP-1 agonists like Wegovy and Zepbound cost $1,000-$1,400 per month. With manufacturer coupons, you might save up to $1,000 a year, but that still leaves $200-$1,000 monthly. Older drugs like phentermine or orlistat cost $10-$150 monthly and are more likely to be covered by insurance.
Do GLP-1 agonists cause nausea?
Yes, nausea is common-20-50% of users experience it, especially when starting or increasing the dose. Vomiting and diarrhea can also occur. Most people adjust over time with slow dose increases, eating smaller meals, and using anti-nausea medication if needed. If side effects are severe, talk to your doctor about lowering the dose or switching.
Can I take GLP-1 agonists if I don’t have diabetes?
Yes. Wegovy and Zepbound are FDA-approved specifically for weight loss in adults with obesity or overweight (BMI ≥30 or ≥27 with at least one weight-related condition), even without diabetes. They were originally developed for diabetes, but their weight loss benefits led to separate approvals for obesity treatment.
What happens if I stop taking a GLP-1 agonist?
Most people regain the weight they lost. Studies show 50-100% of weight loss is regained within a year of stopping. That’s because these drugs don’t cure obesity-they manage it. To keep the weight off, you’ll need to continue the medication, change your eating habits, and stay active. Stopping without lifestyle changes almost always leads to weight regain.
Are there alternatives to injections?
Yes. Oral semaglutide (Rybelsus) is available as a daily pill, but it’s currently only approved for type 2 diabetes-not weight loss. It’s less effective than the injectable versions for weight loss. For now, injectables are the most potent option. Other oral weight loss drugs like Qsymia and Contrave are available but less effective than GLP-1s.
Next Steps
If you’re considering a GLP-1 agonist, start by talking to your doctor. Ask if your BMI qualifies, whether your insurance covers it, and what your out-of-pocket cost might be. Ask about patient assistance programs-Novo Nordisk’s NOW program and Eli Lilly’s Lilly Cares can reduce costs significantly.
If cost is too high, consider older options. Orlistat and phentermine are still useful for some. And if you’ve tried everything and still can’t lose weight, ask about bariatric surgery. It’s not a last resort-it’s a proven solution for severe obesity.
Weight loss isn’t one-size-fits-all. The best drug is the one you can stick with-safely, affordably, and consistently.
Andrea Jones
November 28, 2025 AT 16:12Okay but have you seen the price tag on these things? I’m not even mad-I’m just impressed someone thinks $1,400/month is ‘affordable’ for a pill that makes you feel like you swallowed a live eel.