Several prescription drugs can produce meaningful weight loss, ranging from newer injectable medications that help people lose 14% to 20% of their body weight down to older pills that offer more modest results. The options fall into a few categories: GLP-1 based injectables, combination pills, a fat-blocking capsule, and a handful of medications prescribed off-label. Which ones work best, how they feel to take, and what happens when you stop all vary significantly.
GLP-1 Injectables: The Most Effective Option
The biggest weight loss results come from a class of drugs that mimic a gut hormone called GLP-1. These medications slow stomach emptying, reduce appetite, and change how the brain processes hunger signals. You inject them once a week using a pen device, and the dose gradually increases over several months to reduce side effects.
Semaglutide (sold as Wegovy) produces an average body weight loss of about 13.7% over 72 weeks. Tirzepatide (sold as Zepbound) targets two gut hormones instead of one and delivers roughly 20.2% weight loss over the same period. For someone who weighs 250 pounds, that translates to losing about 34 pounds on semaglutide or 50 pounds on tirzepatide.
The most common side effects are gastrointestinal: nausea, constipation, and abdominal discomfort. These are partly how the drugs work, since they slow the movement of food through your digestive system. More serious but rarer complications include pancreatitis, bowel obstruction, and gastroparesis (a condition where the stomach loses its ability to empty normally). Compared to people taking other weight loss drugs, GLP-1 users had roughly 9 times the rate of pancreatitis and nearly 4 times the rate of gastroparesis in one large analysis. These events are still uncommon in absolute terms, but they’re worth knowing about, especially if you already have digestive issues.
What Happens When You Stop
One of the most important things about GLP-1 drugs is that the weight tends to come back. A meta-analysis of clinical trials found that one year after stopping treatment, people regained about 60% of the weight they had lost. This means these medications work more like blood pressure drugs than antibiotics: they manage the condition while you take them rather than curing it. Many people stay on them long term, which makes cost a major factor.
Without insurance, both Wegovy and Zepbound cost $499 per month when purchased directly from the manufacturers. Zepbound’s lowest starter dose is available for $349. Insurance coverage varies widely, and many plans still don’t cover weight loss medications.
Prescription Combination Pills
Two FDA-approved combination pills offer a middle ground between the dramatic results of injectables and milder options.
Phentermine-topiramate (Qsymia) pairs a stimulant that suppresses appetite with an anti-seizure drug that also blunts hunger. At the higher dose, people lost an average of 9.8% of their body weight over about a year, compared to 1.2% with a placebo. At the lower dose, the result was 7.8%. It’s one of the more effective oral options, though it can cause tingling in the hands and feet, dry mouth, constipation, and changes in taste. It’s not safe during pregnancy because topiramate carries a risk of birth defects.
Naltrexone-bupropion (Contrave) combines a drug used for opioid and alcohol dependence with an antidepressant. It works on brain circuits involved in cravings and reward. Weight loss is more modest than with phentermine-topiramate, typically in the range of 5% to 6% of body weight. Common side effects include nausea, headache, and insomnia. Because it contains bupropion, it shouldn’t be used by people with seizure disorders.
Orlistat: The Fat Blocker
Orlistat takes a completely different approach. Instead of acting on the brain or gut hormones, it blocks enzymes in your intestine from breaking down dietary fat. About 30% of the fat you eat passes through your body undigested. The prescription version (Xenical) and the lower-dose over-the-counter version (Alli) are the only weight loss drugs you can get without a prescription at the lower strength.
The trade-off is that undigested fat has to go somewhere. Oily stools, gas, and urgent bowel movements are common, especially after high-fat meals. Most people learn to eat a lower-fat diet partly to avoid these effects, which itself contributes to the weight loss. Total results are modest, usually around 5% to 7% of body weight over a year.
Off-Label Drugs Used for Weight Loss
Several medications approved for other conditions can cause weight loss as a side effect, and doctors sometimes prescribe them specifically for that purpose.
Phentermine on its own is one of the oldest weight loss drugs, FDA-approved only for short-term use (a few weeks). In practice, some doctors prescribe it longer. In one study, women taking phentermine intermittently lost about 13% of their body weight over 36 weeks, compared to 5% with placebo. It’s a stimulant, so it raises heart rate and blood pressure and can cause insomnia and jitteriness.
Topiramate alone (without the phentermine pairing) can also produce weight loss. A 60-week trial found an 8% placebo-subtracted weight reduction at the highest dose. It’s sometimes prescribed for people who also have migraines or binge eating disorder, since it’s approved for both of those conditions.
Metformin, the most widely prescribed diabetes drug in the world, produces very modest weight loss on its own. In the large Diabetes Prevention Program trial, people taking metformin lost about 4.6 pounds over several years compared to essentially zero with placebo. It works better in people with higher BMIs and at doses above 1,500 mg per day. The weight loss is small, but metformin is inexpensive, well-studied, and has a favorable safety profile, which is why some doctors still suggest it.
Bupropion alone (the antidepressant in Contrave) can produce weight loss of 2% to 5% of body weight, depending on the dose. SGLT2 inhibitors, a class of diabetes drugs that cause you to excrete excess sugar through urine, typically lead to a loss of about 5 to 8 pounds. Zonisamide, another anti-seizure medication, showed a placebo-subtracted loss of about 7 pounds over a year at higher doses.
What May Be Coming Next
Retatrutide, a drug in late-stage clinical trials from Eli Lilly, targets three gut hormones instead of one or two. In a phase 3 trial, participants on the highest dose lost an average of 36.6 pounds. If approved, it could push the weight loss ceiling even higher than current GLP-1 options. Several other drugs with different mechanisms are also in development, though none are available yet.
Comparing Your Options
- GLP-1 injectables (Wegovy, Zepbound): Most effective, 14% to 20% weight loss, weekly injection, $350 to $499/month without insurance, significant GI side effects possible
- Phentermine-topiramate (Qsymia): Best oral option, 8% to 10% weight loss, daily pill, not safe in pregnancy
- Naltrexone-bupropion (Contrave): Moderate results, 5% to 6% weight loss, daily pill, helpful for food cravings
- Orlistat (Xenical/Alli): Blocks fat absorption, 5% to 7% weight loss, available OTC at lower dose, unpleasant GI effects with fatty foods
- Off-label options (metformin, topiramate, bupropion): Smaller effects, 2% to 8% weight loss depending on the drug, often chosen when they also treat another condition
Every weight loss medication works best alongside changes to diet and physical activity. In clinical trials, all groups (including placebo) receive lifestyle counseling, which means the drug results you see reported always include that foundation. The drugs amplify what behavioral changes alone can do, but none of them replace those changes entirely.