Weight Loss Medications

Information on available weight loss drugs, including their efficacy, mechanism, side effects, and costs, is provided at the links below. A table that ranks weight loss treatments (medications and bariatric procedures) by effectiveness is available here - Obesity treatment effects table.

Zepbound and Mounjaro (tirzepatide) 21% weight loss
Efficacy In a 72-week trial enrolling 2539 overweight adults, tirzepatide caused the following weight loss: 15% (5 mg dose), 19.5% (10 mg dose), and 21% (15 mg dose) See tirzepatide (Zepbound) for a comprehensive review
Mechanism Tirzepatide is a once-weekly injection that mimics the actions of GLP-1 and GIP, endogenous hormones released in response to food intake that slow gastric emptying, suppress hunger, and stimulate insulin release
Side effects Side effects of tirzepatide are primarily gastrointestinal. In weight-loss studies, the following was seen: nausea (31%), diarrhea (23%), constipation (12%), vomiting (12%), stomach upset (11%)
Cost Cash pay: Eli Lilly offers a discount card for people whose insurance does not cover Zepbound. In most cases, it will cost $550/month with the card. See Zepbound coverage and cost for more. Insurance: Zepbound: Zepbound is FDA-approved for weight loss, and some plans cover it, while others do not. If prior authorization is required, the form typically asks if the patient meets FDA-approved indications (BMI ≥ 30 or ≥ 27 with comorbidities like hypertension or high cholesterol), and most people are approved. Mounjaro: Mounjaro is only approved to treat diabetes, so its use in weight loss is considered off-label. It is preferred on some insurance plans, which means it can be prescribed without prior authorization. If prior authorization is required, the form will ask if the patient has diabetes and what drugs they have tried. This prevents it from being prescribed for weight loss in nondiabetics.
Availability Eli Lilly has set up a webpage that gives advice on finding Zepbound, along with information on supply issues. See Zepbound availability.

Wegovy and Ozempic (semaglutide) 15 - 17% weight loss
Efficacy In a 68-week trial enrolling 1961 overweight adults, Wegovy caused 15% weight loss. In other similar studies, Wegovy caused 16 - 18% weight loss. Wegovy and Ozempic contain the same active ingredient, semaglutide. The only difference between the products is their dosage forms. Wegovy comes in 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, and 2.4 mg strengths, while Ozempic is available in 0.25 mg, 0.5 mg, 1 mg, and 2 mg strengths. See Wegovy for a comprehensive review
Mechanism Semaglutide is a once-weekly injection that mimics the actions of GLP-1, an endogenous hormone released in response to food intake that slows gastric emptying, suppresses hunger, and stimulates insulin release
Side effects Side effects of semaglutide are primarily gastrointestinal. In weight-loss studies, the following was seen: nausea (44%), diarrhea (30%), vomiting (24%), constipation (24%), abdominal pain (20%)
Cost Cash pay: around $1000/month Insurance: Wegovy: Wegovy is FDA-approved for weight loss, and some plans cover it, while others do not. If prior authorization is required, the form typically asks if the patient meets FDA-approved indications (BMI ≥ 30 or ≥ 27 with comorbidities like hypertension or high cholesterol), and most people are approved. The Wegovy manufacturer has set up a webpage to help determine insurance coverage - Wegovy coverage checker. Some compounding pharmacies offer what has been called "bootleg Wegovy" at a greatly reduced price. It's unclear where these pharmacies are getting semaglutide, and the legality is questionable since it is a patent-protected compound. In May 2023, the FDA issued a warning about these compounded versions - FDA warning on compounded semaglutide Ozempic: Ozempic is only approved to treat diabetes, so its use in weight loss is considered off-label. It is preferred on some insurance plans, which means it can be prescribed without prior authorization. If prior authorization is required, the form will ask if the patient has diabetes and what drugs they have tried. This prevents it from being prescribed for weight loss in nondiabetics.

Phentermine (appetite suppressants) 10% weight loss
Efficacy In 3 to 6 month studies enrolling overweight adults, phentermine and similar appetite suppressants caused about 10% weight loss See appetite suppressants for a comprehensive review
Mechanism Appetite suppressants are stimulants that work by blocking hunger pathways in the hypothalamus. Phentermine has been available since the 1950s and is one of the most widely prescribed drugs ever.
Side effects Side effects of phentermine are related to its stimulant properties and include insomnia, dry mouth, palpitations, anxiety, agitation, and increased heart rate. See phentermine patient information (pdf) for more. In the 1990s, phentermine was combined with a drug called fenfluramine in the popular "Phen-fen" diet pill. Fenfluramine was later pulled from the market because it increased the risk of heart valve disease. In studies, phentermine has not been definitively linked with any type of heart or lung problems.
Cost Cash pay: around $12/month Insurance: insurance coverage isn't relevant since cash pricing is affordable

Qsymia (phentermine + topiramate) 10% weight loss
Efficacy In a 56-week study enrolling 2487 overweight adults, Qsymia (15/92 mg) caused 9.8% weight loss See Qsymia for a comprehensive review
Mechanism Qsymia is a daily capsule containing both immediate-release phentermine and extended-release topiramate. Phentermine is an appetite suppressant, and topiramate is a seizure medication that suppresses hunger through an unknown mechanism. At its highest dose, Qsymia contains 15 mg/day of phentermine, which is less than half the standard daily dose of 37.5 mg.
Side effects Side effects of Qsymia include dry mouth (21%), tingling sensation in the fingers (21%), taste perversion (10%), insomnia (10%), and dizziness (10%). The Qsymia prescribing information recommends that electrolytes be measured before and during therapy to check for metabolic acidosis, a potential side effect of topiramate.
Cost Cash pay: the Qsymia® manufacturer has set up a website that allows cash-pay patients to get Qsymia for $98/month (Qsymia Home Delivery Pharmacy). However, it's usually cheaper to prescribe the individual components (phentermine and topiramate) separately since they both have cheap generics. Insurance: insurance coverage varies

Saxenda (liraglutide) 8% weight loss
Efficacy In a 56-week study enrolling 3731 overweight adults, Saxenda caused 8% weight loss See Saxenda for a comprehensive review
Mechanism Saxenda is a daily injection that mimics the actions of GLP-1, an endogenous hormone released in response to food intake that slows gastric emptying, suppresses hunger, and stimulates insulin release Saxenda is in the same class as Wegovy and Ozempic. It was approved for weight loss in 2014, but its effects are not as pronounced as the newer GLP-1 therapies, so it was not as highly touted.
Side effects Saxenda side effects are primarily gastrointestinal. In weight-loss trials, the following was seen: nausea (40%), diarrhea (21%), constipation (20%), vomiting (16%), and upset stomach (10%).
Cost Cash pay: around $1400/month Insurance: Few insurance plans cover Saxenda. The manufacturer has a webpage to help determine insurance coverage (Saxenda coverage checker).

Xenical and Alli (orlistat) 7.6% weight loss
Efficacy In a two-year study enrolling 729 overweight adults, orlistat caused the following weight loss: 6.8% (60 mg dose) and 7.6% (120 mg dose) See orlistat for a comprehensive review
Mechanism Xenical and Alli, capsules taken three times daily with meals, contain orlistat, a lipase inhibitor. Lipase is an enzyme secreted into the intestinal lumen by the pancreas and stomach. Lipase breaks down dietary fat so that it can be absorbed systemically. Orlistat inhibits lipase, thus reducing intestinal fat absorption by as much as 30% (120 mg dose).
Side effects Reduced fat absorption can cause a variety of gastrointestinal symptoms, including oily rectal spotting (27%), flatus with discharge (24%), fecal urgency (22%), oily evacuation (20%), and fatty/oily stools (17%). These side effects usually improve over time, with all dropping to less than 5% after a year. The absorption of fat-soluble vitamins (A,D,E,K) may also be reduced, so it's recommended that patients take a daily multivitamin at least two hours before orlistat.
Cost Cash pay: Alli (60 mg) is available over-the-counter, and Xenical (120 mg) is by prescription only. Xenical has no generic and costs around $800/month. Alli costs about $50/month. Insurance: Few insurance plans cover Xenical

Plenity (hydrogel) 6.4% weight loss
Efficacy In a 24-week study enrolling 436 overweight adults, Plenity caused 6.4% weight loss See Plenity for a comprehensive review
Mechanism Plenity capsules contain particles of a nonsystemic superabsorbent hydrogel composed of cellulose and citric acid. Once the particles are released in the stomach, they absorb 100 times their original weight and occupy about a quarter of the average stomach. The hydrated particles then mix with ingested food to increase its volume; theoretically, this enhances fullness and satiety. The particles maintain their gel form as they pass through the small intestine into the colon, where they are degraded, and released water is reabsorbed. The degraded particles are then eliminated in the stool. See How Plenity Works (YouTube).
Side effects Plenity side effects include diarrhea (13%), abdominal distension (12%), infrequent bowel movements (9%), flatus (9%), and abdominal pain (5%)
Cost Cash pay: any doctor can prescribe Plenity, but it is only available through GoGoMeds, a mail-order pharmacy (GoGoMeds website). A four-week supply costs $98. Insurance: not covered

Contrave (bupropion + naltrexone) 6.1% weight loss
Efficacy In a 56-week study enrolling 1742 overweight adults, Contrave caused 6.1% weight loss See Contrave for a comprehensive review
Mechanism Contrave is a tablet containing bupropion, an antidepressant, and naltrexone, an opioid antagonist. It's unclear how either drug suppresses hunger, but nonclinical studies suggest that naltrexone and bupropion affect two separate areas of the brain involved in regulating food intake: the hypothalamus (appetite regulatory center) and the mesolimbic dopamine circuit (reward system).
Side effects Common side effects of Contrave include nausea (33%), constipation (19%), headache (18%), vomiting (11%), dizziness (10%), and insomnia (9%) Patients should also be aware that naltrexone blocks the analgesic effect of opioid medications (e.g. morphine, hydrocodone). In emergency situations, the blockage can be overridden with higher opioid doses, or other analgesic classes can be used.
Cost Cash pay: the Contrave manufacturer has set up a website that allows cash-pay patients to get Contrave for $99/month through a mail-order pharmacy (Contrave CurxAccess program). However, it's usually cheaper to prescribe the individual components (bupropion and naltrexone) separately since they both have cheap generics. Insurance: few insurance plans cover Contrave

Other drugs touted as weight loss treatments

Metformin - metformin is a widely-prescribed diabetes medication that increases insulin sensitivity. Even though some providers tout it as a weight-loss drug, it has never been shown in a clinical trial to cause meaningful weight loss. Vitamin B12 - vitamin B12 is recommended by some to promote weight loss. It has never been proven to cause weight loss or increase energy in a clinical trial. Rybelsus (semaglutide) - Rybelsus is an oral form of semaglutide approved to treat diabetes. In a 26-week diabetes study, it caused 4.2% (14 mg dose) weight loss. HCG - HCG (human chorionic gonadotropin) is a hormone released by pregnant women that has been promoted for decades as a weight-loss treatment. In small studies, weight loss with HCG was no better than placebo.

Future therapies

Retatrutide - Eli Lilly is developing a triple-hormone-receptor agonist (GLP, GIP, and Glucagon) called retatrutide that is given as a once-weekly injection. In a 48-week study enrolling 338 overweight adults, the highest dose of retatrutide caused 24.2% weight loss. [PubMed abstract] Oral semaglutide - Novo Nordisk is developing a 50-mg oral version of semaglutide. In a 68-week trial enrolling 667 overweight adults, oral semaglutide caused 15.1% weight loss. [PubMed abstract] Semaglutide + cagrilintide - Novo Nordisk is developing an injection that contains semaglutide and cagrilintide, an amylin analog. In a 32-week study enrolling 92 overweight diabetics, the injection caused 15.6% weight loss. [PubMed abstract] Orforglipron - Eli Lilly is developing a once-daily oral GLP agonist called orforglipron. In a 36-week study enrolling 272 overweight adults, the highest dose of orforglipron caused 14.7% weight loss. [PubMed abstract] Danuglipron - Pfizer is studying an oral GLP-1 agonist called danuglipron, which it hopes to get approved for diabetes and obesity. Weight-loss studies have not been published yet, but development of a twice-daily version was recently abandoned because of excessive side effects. [Medscape article]

• BPD/DS - Biliopancreatic diversion with duodenal switch
• References [PMID: 32202076, 33625476, 28017964, 19564877, 21481449, 26132939, 10678259, 20673995, 30421844, 35658024]

Typical weight loss seen with obesity treatments
Treatment	% weight loss from baseline (length of follow-up)
BPD/DS	35 - 40% (> 10 years)
Gastric bypass	30 - 35% (> 10 years)
Gastric sleeve	25 - 30% (> 10 years)
Gastric banding	20 - 25% (> 10 years)
Zepbound and Mounjaro (tirzepatide)	21% (72 weeks)
Wegovy (semaglutide)	16% (68 weeks)
Endoscopic sleeve gastroplasty	11.4% (104 weeks)
Intragastric balloon	10% (6 months)
Appetite suppressants (e.g. phentermine)	10% (6 months)
Qsymia (topiramate + phentermine)	10% (56 weeks)
Saxenda (Liraglutide)	8% (56 weeks)
Xenical (orlistat)	7.6% (2 years)
Plenity (hydrogel)	6.4% (24 weeks)
Contrave (naltrexone + bupropion)	6.1% (56 weeks)

Weight loss therapies from Texas Telemedicine Doctor