WEIGHT LOSS DRUGS - Where are we now?
A review of available weight loss drugs, including efficacy, costs, side effects, and insurance coverage
Straight Healthcare
March 2023
With 42% of the U.S. adult population being obese, it's no secret that millions of people struggle with their weight. Our ancestors weren't nearly as fat, so something has changed that has made us pack on the pounds. Experts point to a variety of factors, including contemporary work life (e.g. sitting at computers), widespread availability of high-calorie processed foods, lack of education, busy schedules with no time for exercise, and on and on. I think most realists will agree that people know they should eat less and exercise more, they just don't do it. Whatever the reason, it doesn't really matter because the problem exists and people's health suffers greatly from it.
When diet and exercise fail, patients turn to doctors for help. Weight loss drugs have been around for over half a century, and some had checkered pasts, leaving many providers wary of prescribing them. Besides, if they really worked, wouldn't everyone be skinny? Recently, the GLP-1 drugs have revived the weight-loss-drug discussion, and demand for these "miracle" injections has outpaced supply. So how do the new drugs stack up to the old, and what are the costs, side effects, and availability? We break it down for you below.
First, let's look at their efficacy. The table below shows the average weight loss in trials for every available drug. Weight loss from bariatric procedures is included for comparison's sake.
The two GLP-1 drugs, Mounjaro and Wegovy, are most effective with 16 - 21% weight loss, but not far behind at 10% is phentermine, which has been around since the 1950s and costs less than $10 a month. Qsymia, a combination of phentermine and topiramate, also comes in at 10%, followed by Saxenda (8%), Xenical (7.6%), Contrave (6.5%), and Plenity (6.4%). Below, we examine each drug individually and take a look at side effects and costs.
GLP-1 drugs | 8 - 21% weight loss - The GLP-1 drugs include Mounjaro, Wegovy, Ozempic, and Saxenda. Wegovy, Ozempic, and Saxenda mimic the action of GLP-1, an endogenous hormone released in response to food intake that slows gastric emptying, suppresses hunger, and stimulates insulin release. Mounjaro has a dual action, mimicking GLP-1 and a similar hormone called GIP (see GLP therapies for more). GLP-1 drugs were originally developed to treat diabetes, and when it was noted that they caused significant weight loss, their use in obesity was explored. Saxenda was FDA-approved for weight loss in 2014, and Wegovy was approved in 2021. Weight loss from Saxenda is not as impressive as Wegovy (16% vs 8%), so it did not make as big a splash. Mounjaro is the most effective at 21%, but it is currently only approved for diabetes; a weight loss indication will be coming soon. Wegovy and Ozempic contain the same active drug, semaglutide. But Ozempic is only approved for diabetes, so its use in obesity is considered off-label. The maximum recommended dose of Ozempic was recently increased to 2 mg once weekly, making it similar to Wegovy (2.4 mg once weekly).
Side effects - Side effects from GLP drugs are primarily gastrointestinal. In Wegovy trials, the following was seen: nausea (44%), diarrhea (30%), vomiting (24%), constipation (24%), abdominal pain (20%), and dyspepsia (9%).
Appetite suppressants (e.g. phentermine) | 10% weight loss - Appetite suppressants are believed to work by blocking hunger pathways in the hypothalamus. Phentermine, which has been around since the 1950s, is by far the most popular drug in this class. In the 1990s, it was combined with a drug called fenfluramine in the popular "Phen-fen" diet pill. Fenfluramine was later pulled from the market because it was associated with heart valve disease. This, along with the fact that phentermine is a controlled substance, has created some misconceptions about the drug. You can read more on that here - phentermine myths and realities.
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.
Costs - phentermine typically costs $10/month or less, making it the most cost-effective weight loss drug for cash-pay patients
Qsymia (phentermine + topiramate) | 10% weight loss - Qsymia is a capsule containing both immediate-release phentermine and extended-release topiramate. Phentermine is an appetite suppressant (see above), 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.
Costs - the 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.
Xenical and Alli | 7.6% weight loss - Xenical and Alli 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 with continued use, with all dropping to < 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 concomitant multivitamin at least two hours before orlistat.
Costs - Alli (60 mg) is available over-the-counter, and Xenical (120 mg) is by prescription only. Xenical has no generic and is expensive, and Alli costs about $50 a month.
Contrave (bupropion + naltrexone) | 6.5% weight loss - Contrave is a combination of 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 classes of analgesics can be used.
Costs - the 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.
Plenity | 6.4% weight loss - 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 YouTube video on how Plenity works.
Side effects - Plenity side effects include diarrhea (13%), abdominal distension (12%), infrequent bowel movements (9%), flatus (9%), and abdominal pain (5%).
Costs - Any doctor can prescribe Plenity, but it can only be filled by GoGoMeds, a mail-order pharmacy (GoGoMeds website). A four-week supply costs $98.
When diet and exercise fail, patients turn to doctors for help. Weight loss drugs have been around for over half a century, and some had checkered pasts, leaving many providers wary of prescribing them. Besides, if they really worked, wouldn't everyone be skinny? Recently, the GLP-1 drugs have revived the weight-loss-drug discussion, and demand for these "miracle" injections has outpaced supply. So how do the new drugs stack up to the old, and what are the costs, side effects, and availability? We break it down for you below.
First, let's look at their efficacy. The table below shows the average weight loss in trials for every available drug. Weight loss from bariatric procedures is included for comparison's sake.
| Average weight loss in trials for 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) |
| 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) |
| Contrave (naltrexone + bupropion) | 6.5% (28 weeks) |
| Plenity (hydrogel) | 6.4% (24 weeks) |
GLP-1 drugs | 8 - 21% weight loss - The GLP-1 drugs include Mounjaro, Wegovy, Ozempic, and Saxenda. Wegovy, Ozempic, and Saxenda mimic the action of GLP-1, an endogenous hormone released in response to food intake that slows gastric emptying, suppresses hunger, and stimulates insulin release. Mounjaro has a dual action, mimicking GLP-1 and a similar hormone called GIP (see GLP therapies for more). GLP-1 drugs were originally developed to treat diabetes, and when it was noted that they caused significant weight loss, their use in obesity was explored. Saxenda was FDA-approved for weight loss in 2014, and Wegovy was approved in 2021. Weight loss from Saxenda is not as impressive as Wegovy (16% vs 8%), so it did not make as big a splash. Mounjaro is the most effective at 21%, but it is currently only approved for diabetes; a weight loss indication will be coming soon. Wegovy and Ozempic contain the same active drug, semaglutide. But Ozempic is only approved for diabetes, so its use in obesity is considered off-label. The maximum recommended dose of Ozempic was recently increased to 2 mg once weekly, making it similar to Wegovy (2.4 mg once weekly).
Side effects - Side effects from GLP drugs are primarily gastrointestinal. In Wegovy trials, the following was seen: nausea (44%), diarrhea (30%), vomiting (24%), constipation (24%), abdominal pain (20%), and dyspepsia (9%).
Costs / Insurance coverage - Cash pricing for each drug is around $1000 a month. For people with insurance, the following is typically true:
- Wegovy - The Wegovy manufacturer has a webpage to help determine insurance coverage (Wegovy coverage checker). Anecdotally, my patients have had mixed results getting correct information from it. If insurance requires a prior authorization, it typically goes one of two ways: (1) the form asks if the patient meets approved indications (BMI ≥ 30 or ≥ 27 with comorbidities like hypertension or high cholesterol), in which case, most people are approved, (2) the form asks if the patient has tried a long list of other therapies (proof is often required), in which case, most people don't qualify and it is denied. 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. See this NBC News article for more - People are buying copycat versions of Ozempic and Wegovy. Is that safe?, NBC News, Mar 19th, 2023
- Ozempic and Mounjaro - Ozempic and Mounjaro are only approved to treat diabetes, so their use in weight loss is considered off-label. They are preferred on some insurance plans, which means they can be prescribed without a prior authorization. If a prior authorization is required, it will ask if the patient has diabetes and what drugs they have tried. This prevents them from being prescribed for weight loss in nondiabetics.
- Saxenda - The Saxenda manufacturer has a webpage to help determine insurance coverage (Saxenda coverage checker). Saxenda contains liraglutide, which is also found in the diabetes drug Victoza. Dosage forms and dosing are different, though, so they are not typically substituted for each other.
Appetite suppressants (e.g. phentermine) | 10% weight loss - Appetite suppressants are believed to work by blocking hunger pathways in the hypothalamus. Phentermine, which has been around since the 1950s, is by far the most popular drug in this class. In the 1990s, it was combined with a drug called fenfluramine in the popular "Phen-fen" diet pill. Fenfluramine was later pulled from the market because it was associated with heart valve disease. This, along with the fact that phentermine is a controlled substance, has created some misconceptions about the drug. You can read more on that here - phentermine myths and realities.
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.
Costs - phentermine typically costs $10/month or less, making it the most cost-effective weight loss drug for cash-pay patients
Qsymia (phentermine + topiramate) | 10% weight loss - Qsymia is a capsule containing both immediate-release phentermine and extended-release topiramate. Phentermine is an appetite suppressant (see above), 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.
Costs - the 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.
Xenical and Alli | 7.6% weight loss - Xenical and Alli 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 with continued use, with all dropping to < 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 concomitant multivitamin at least two hours before orlistat.
Costs - Alli (60 mg) is available over-the-counter, and Xenical (120 mg) is by prescription only. Xenical has no generic and is expensive, and Alli costs about $50 a month.
Contrave (bupropion + naltrexone) | 6.5% weight loss - Contrave is a combination of 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 classes of analgesics can be used.
Costs - the 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.
Plenity | 6.4% weight loss - 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 YouTube video on how Plenity works.
Side effects - Plenity side effects include diarrhea (13%), abdominal distension (12%), infrequent bowel movements (9%), flatus (9%), and abdominal pain (5%).
Costs - Any doctor can prescribe Plenity, but it can only be filled by GoGoMeds, a mail-order pharmacy (GoGoMeds website). A four-week supply costs $98.
