When it comes to losing weight, pills alone rarely do the job. But in the last few years, a new wave of medications has changed the game. GLP-1 agonists like Wegovy, Zepbound, and Saxenda aren’t just another trend-they’re reshaping how we treat obesity. Yet they’re not the only option. Older drugs like orlistat, Qsymia, and Contrave have been around for decades. So which one actually works better? And more importantly, which one works 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 food leaves your stomach. It also helps your pancreas release insulin only when you need it, which is why these drugs were first developed for type 2 diabetes.
Now, they’re being used for weight loss because they cut cravings hard. People don’t just eat less-they stop thinking about food as much. Semaglutide (Wegovy) and tirzepatide (Zepbound) are the heavyweights here. In clinical trials, people lost 15% to 21% of their body weight. That’s not a few pounds. For someone weighing 200 pounds, that’s 30 to 40 pounds gone. And it’s not magic. It’s biology.
These drugs are injected once a week. You start with a tiny dose-0.25 mg for semaglutide-and slowly increase it over four to five months. This slow ramp-up is key. It’s not just about getting to the right dose; it’s about letting your body adjust so you don’t end up sick. About half of users get nausea, vomiting, or diarrhea early on. Most of it fades as your system gets used to it.
Older Weight Loss Drugs: The Basics
Before GLP-1s, the options were limited. Orlistat (Xenical, Alli) works by blocking fat absorption. Whatever fat you eat that your body can’t digest just... exits. It’s messy. You might notice oily stools or urgent bowel movements, especially if you eat fried food. It’s not glamorous, but it works-on average, people lose 5% to 10% of their weight.
Phentermine-topiramate (Qsymia) is a combo pill. Phentermine is an old-school stimulant that suppresses appetite. Topiramate, originally an anti-seizure drug, also reduces hunger and makes you feel full faster. Together, they help people lose around 10% of their body weight. But they come with side effects: dry mouth, tingling in fingers and toes, trouble sleeping, and in rare cases, mood changes.
Naltrexone-bupropion (Contrave) targets the brain’s reward system. It doesn’t make you feel full-it makes food less rewarding. You still eat, but you don’t crave it as much. It’s effective for about 5% to 8% weight loss, but it can cause headaches, constipation, and nausea. And like all these drugs, it only works if you stick with it.
Head-to-Head: Efficacy
Let’s cut through the noise. Numbers don’t lie.
Wegovy (semaglutide) led to 14.7% weight loss in 36 weeks. Zepbound (tirzepatide) pushed past 20% in 72 weeks. That’s not a small difference. It’s the difference between fitting into one size smaller and going down two sizes.
Compare that to Saxenda (liraglutide), an earlier GLP-1 drug. It averages 8% weight loss. Still better than most older drugs, but nowhere near the newer ones.
Now look at the old guard:
- Orlistat: 5-10% weight loss
- Qsymia: ~10% weight loss
- Contrave: 5-8% weight loss
Even the best of the old drugs struggle to hit double digits. GLP-1 agonists aren’t just slightly better-they’re in a different league.
And here’s something shocking: a direct comparison showed Wegovy users lost 16% of their weight versus 6% with Saxenda. That’s more than double the results. It’s not even close.
Cost: The Hidden Barrier
There’s a reason you hear so much about these drugs on social media-and so little about them at your local pharmacy. Price.
Without insurance, GLP-1 agonists cost $1,000 to $1,400 a month. That’s $12,000 to $16,800 a year. For most people, that’s impossible. Even with insurance, many plans won’t cover them unless you have diabetes or a BMI over 40 (or 35 with other health issues). A 2024 poll found only 28% of commercial insurance plans cover these drugs for weight loss without strict rules.
Older drugs? Not even close. Orlistat costs $50 a month. Qsymia runs $100-$150. Phentermine? As low as $10-$30. Many are available as generics. Insurance covers them more often. They’re not perfect, but they’re affordable.
And let’s not forget: manufacturer coupons exist for GLP-1s, but they cap savings at $500-$1,000 a year. That’s still thousands out of pocket.
Real-World Results vs. Clinical Trials
Here’s where things get messy. Clinical trials are run under perfect conditions: patients are monitored, dosed precisely, and followed closely. Real life? Not so much.
A study from NYU Langone Health tracked people on GLP-1s for a year. The average weight loss? Just 7%. That’s less than half of what the trials promised. Why? Two big reasons: side effects and cost.
Up to 70% of people stop taking GLP-1 drugs within a year. Some can’t handle the nausea. Others just can’t afford it. And if you stop? Weight comes back fast. Studies show 50% to 100% of lost weight returns within a year of stopping.
Older drugs have lower dropout rates-not because they’re better, but because they’re cheaper and easier to tolerate. You can take a pill without needles. You can skip a day without feeling like you’re losing control. But they also don’t deliver the same results.
Who These Drugs Are For
Not everyone needs-or should-take a GLP-1 agonist.
If you’re looking for dramatic weight loss and can afford it, these drugs are the most powerful option we have outside of surgery. They’re especially helpful if you also have type 2 diabetes, high blood pressure, or heart disease-because they help with those too.
If you hate needles, can’t handle nausea, or are on a tight budget, older drugs might be your best bet. They’re not glamorous, but they’re real. And for some people, losing 8% of their body weight is life-changing.
And here’s something important: even if you’re considering bariatric surgery, GLP-1s are now being used before and after. Johns Hopkins found one in seven post-surgery patients started these drugs to maintain weight loss. They’re not replacing surgery-they’re complementing it.
What’s Coming Next
The science is moving fast. Retatrutide, a triple-acting drug targeting GLP-1, GIP, and glucagon, showed 24.2% weight loss in early trials. That’s more than bariatric surgery in some cases. MariTide, a new monoclonal antibody, is now in Phase 3 trials with promising early results.
But with innovation comes questions. What happens when patents expire after 2030? Will generics bring prices down? Will insurance finally cover these drugs for more people? Right now, the system is broken. The drugs work. But access is uneven.
Final Thoughts
GLP-1 agonists are a revolution. They’re not perfect, but they’re the most effective weight loss drugs ever developed. They’re not magic. They’re medicine. And like all medicine, they come with trade-offs.
Older drugs are still useful. They’re affordable. They’re accessible. They’re real. But they don’t compete with the power of semaglutide or tirzepatide.
The real question isn’t which drug is better. It’s: what’s your goal? What’s your budget? What can you live with? Because no pill works unless you can stick with it.