What Medications Can Help Me Lose Weight?

Which Medications Can Facilitate Weight Loss?

“I’ve tried everything, and I just can’t keep the weight off.” How often have you felt this way? You’ve tried multiple diets, reduced your calories, eaten your veggies, worked out faithfully at the gym, taken the stairs instead of the elevator —and yet nothing seems to change, especially over the long term. As we’ve discussed in earlier modules, there are multiple reasons why it can be difficult to lose weight, including our body’s own desire to maintain the status quo. Several theories try to account for why it’s so difficult to lose and to maintain weight. Our brain controls both our energy intake and expenditure through complex signaling of our nervous system with neurotransmitters, endorphins, hormones, reward systems of pleasurable stimuli in the mesocorticolimbic dopamine systems, and through feedback loops with signals, such as leptin and ghrelin. People with obesity have a variety of ways in which they respond to hunger and to satiety cues as well as emotional and reward cues, compared to those who are not obese (Yanowski & Yanowski, 2014). Certainly, there are strong behavioral components, such as eating more calories than needed, losing motivation to maintain a restrictive diet, and failing to exercise regularly. Other factors, including biological factors such as your metabolism slowing down (adaptive thermogenesis) and your hunger increasing, are also involved. There are reductions in leptin and cholecystokinin, and increases in ghrelin. This is our body’s way of maintaining a balance (homeostasis), but it works against our need and desire to decrease fat and improve our health (Ladensheim, 2015). Scientific evidence reveals that the body will try to return to its highest lifetime weight; through neurochemical signaling and hormonal changes, the hypothalamus slows down energy expenditure and increases appetite to try to adapt to a restrictive calorie diet. These hormonal and neurochemical adaptations can be permanent, making it very difficult for a person with obesity to ever maintain weight in a way that a person who has never been obese can. This might be why obesity tends to be a chronic disease that needs long-term management (Sumithran et al, 2011).

People with obesity often believe, and are subject to, the attitude that obesity is a lifestyle, rather than a disease. The science of obesity has been developing, with new findings coming out every day about the complex interplay among genetics, behavior, mood, environment, the mind, the gut, and neurotransmitters and hormones that keep our energy in and energy out; that is, in—or out of— balance. This opinion, that obesity is a lifestyle issue, is prevalent throughout the general population as well as with many clinicians who haven’t had training in obesity management with lifestyle interventions and pharmacology. Many people with obesity have a difficult time finding an appropriate and affordable intervention with professional behaviorists, nutritionists, and exercise specialists, and are left to tackle obesity on their own. The long-term use of medications in other chronic illnesses is well accepted but it is less commonplace with obesity for a variety of reasons. Obesity drugs have a somewhat checkered past, with some removed from the market due to dangerous side effects or the potential for abuse. This leaves many clinicians reluctant to prescribe an anti-obesity medication, especially a newer drug, with limited long- term safety and efficacy data. Their patients might already be on other medications and adding yet another medicine can lead to adverse effects; it might not be clear that the benefits of prescribing outweigh the risks. The medications can be expensive, and insurance is often unwilling to pay for them. From the patient’s perspective, the anti-obesity drugs are not always easy to take, and many have side effects. The effectiveness of the medications vary greatly from individual to individual, and moderate weight loss is not always valued or seen as a “success.” Also, like use of any long-term medication, it requires surveillance, with the time and expense of visiting their clinician periodically (Cefalu et al, 2015).

Although lifestyle interventions, including diet and exercise, will always form the foundation of weight loss and maintenance, there are six US Food and Drug Administration (FDA)–approved medications for the treatment of obesity. These prescription medications can help with the likelihood and the amount of weight lost, beyond what diet and exercise alone can do. These medications include:

For long-term use:

  • Liraglutide 3.0 mg (Saxenda)
  • Lorcaserin (Belviq)
  • Naltrexone/bupropion SR (Contrave)
  • Orlistat (Xenical—prescribed; Alli—over-the-counter) 
  • Phentermine/topiramate (Qsymia)

For short-term use only:

  • Phentermine (Lomaira/Adipex) 
  • Phendimetrazine 
  • Benzphetamine 
  • Diethylpropion

How Do These Medications Work?

Each of these medications works in a different way to help you lose weight. Most are small molecules that cross the blood–brain barrier and activate a neurochemical cascade in the brain, with some efficacy toward causing weight loss but also other central nervous system (CNS) effects, as well. Newer weight- loss medications are more targeted, mimicking the body’s hormones from the gut–brain axis. None are “magic pills,” but in conjunction with a healthy diet and regular exercise, they have been shown to result in some degree of weight loss. Most of the medications work by doing the following:

  • Reducing your appetite so that you eat fewer calories Reducing the absorption of your food, especially fat
  • Increasing your energy expenditure, by boosting your metabolism (e.g., by raising your body temperature)
  • Mimicking calorie restriction (Chiba et al, 2010).

We briefly review the mechanism of action of each FDA-approved obesity medication.

Long-term medications for obesity:

  • Liraglutide 3.0 mg, marketed as Saxenda, is an injectable drug that is used to treat diabetes; it was approved in 2015 for weight loss. It slows down the rate of food leaving your stomach, keeps your liver from making too much glucose and helps your pancreas make more insulin, thereby lowering your blood glucose. The glucagon-like peptide (GLP- 1) mimics a hormone that activates a part of your brain that regulates your appetite. It helps you feel less hungry, leading to eating less, and resulting in weight loss (Ladensheim, 2015).
  • Lorcaserin is sold as Belviq, and it works by selectively activating a type of serotonin receptor found in your brain, the 5-HT2c receptor.
  • Triggering the 5-HT2c receptors in the hypothalamus is thought to
  • stimulate the pro-opiomelanocortin (POMC) brain cells that produce alpha-melanocyte stimulating hormone (α–MSH). The α–MSH activates the melanocortin4 receptors (MC4R), which induces satiety, or a sense that you are not hungry, and might also increase your energy expenditure, burning more calories (https://doi.org/10.1358/dot.2010.46.12.1556433).
  • Naltrexone/bupropion is the generic name for Contrave, a combination of medications that work in the brain in several ways to help with weight loss. The hypothalamic melanocortin system and the mesolimbic reward system regulate food intake and body weight through a feedback loop. The POMC brain cells in the hypothalamus release both α–melanocyte-stimulating hormone (MSH) and β-endorphins. These work in opposite ways to regulate hunger, with the MSH/MC4R decreasing appetite and the β-endorphins encouraging pleasure eating. The α–MSH activates the MC4Rs; the activated MC4Rs decrease your appetite. The POMC cells also release β-endorphins, which are our own natural opioids that are activated by “rewards,” such as sugary and high-fat foods. The β- endorphins can inactivate the anorectic effect of the MC4Rs through feedback loops, leading to your eating foods that activate the internal opioid system. Bupropion is a dopamine and norepinephrine re-uptake inhibitor (NDRI), which increases the dopamine and norepinephrine concentrations in the brain. It is hypothesized that hypothalamic dopamine stimulates the POMC MC4R neurons that can decrease food cravings. Bupropion also influences energy expenditure by increasing the body’s heat production. Naltrexone is a μ-opioid antagonist that prevents β-endorphins from undoing the anorectic effect of the MC4Rs. Naltrexone also prevents an increase in dopamine in the brain’s mesolimbic reward system in the nucleus accumbens. This prevents the pleasure (i.e., increased dopamine) in reward-eating binges on foods high in sugar and fat. The combination of the two drugs, naltrexone and bupropion, produces a greater reduction in food intake than either drug administered alone (Billes et al, 2014).
  • Orlistat is marketed as a prescription drug, Xenical, and as an over-the- counter medication as Alli, which is a reduced dose from the prescribed drug. Orlistat is a pancreatic lipase inhibitor. It works in the gastrointestinal (GI) tract by binding to lipase, an enzyme produced by the pancreas that breaks down fats. Orlistat reduces lipase’s ability to break down triglycerides into components that are normally absorbed. Fats that aren’t absorbed leave your body through bowel movements (Lunagariya et al, 2014; Derosa et al, 2016).
  • Phentermine/topiramate ER, a combination drug prescribed as Qsymia, was the first combination drug approved by the FDA for obesity, in 2012. Phentermine is similar to amphetamine, in that it triggers the release of norepinephrine into the neural synapses and to a lesser extent, dopamine and serotonin. Its main effect is to decrease the sensation of hunger primarily by modulating the effect on the hypothalamus, and it might also increase energy expended to boost metabolism. Topiranate (Topamax) is an anti-seizure drug known to be correlated with weight loss. The mechanism of action of topiramate is unknown, but it is believed to influence the neurotransmitters that regulate appetite and satiety by increasing gamma amino butyric acid (GABA) activity and carbonic anhydrase inhibition (Lonneman et al, 2013).

Short-term medications for obesity:

  • Phentermine, also sold as Adipex, is the most frequently prescribed medication for weight loss. It is a sympathomimetic, similar to amphetamine. It was first approved by the FDA in 1959 and marketed for several years as part of fen-phen, which was taken off the market in 1997 because fenfluramine was found to cause pulmonary hypertension and valvular heart disease in a significant number of people taking the drug. Since then, phentermine has been prescribed alone as a psychostimulant that increases your heart rate and blood pressure and decreases appetite.
  • Phendimetrazine is another sympathomimetic that works in your brain to decrease appetite. It is marketed as Bontril and Melfiat.
  • Benzphetamine is marketed as Didrex and Regimex. It is also a sympathomimetic, similar in action to phentermine. It blunts appetite.
  • Diethylpropion, prescribed only as a generic medication, is also a sympathomimetic, similar in action to phentermine. It blunts appetite.

Off-label prescription medications:

  • Metformin is a generic diabetes treatment usually sold as Glucophagae which may help people with diabetes or those who have gained weight (e.g., from use of antipsychotics) lose weight. It’s mechanism of action is not completely understood, but it is believed to be related to lowering blood glucose, which decreases the insulin burden that triggers hunger, leading to a lower calorie intake. It also appears to affect how fat is processed and stored.
  • Topiramate is a generic anti-seizure drug once used for epilepsy and now more commonly for the prevention of migraines. It has multiple effects on the brain that result in a decreased appetite. It is now often used as part of a combination medication, phentermine and topiramate.
  • Zonisamide is an anti-seizure drug that has effects on serotonin and dopamine; it also blocks calcium and sodium channels. It was identified as causing weight reduction during clinical trials for epilepsy, as an adverse effect. Its exact mechanism of action is unknown, but it appears to alter the sense of taste.
  • Fluoxetine, also known as Prozac, is a selective serotonin re-uptake inhibitor (SSRI) that can cause weight loss in some individuals (typically those who are underweight or who have an eating disorder). Its mechanism of action is not known, but it can cause a decrease in appetite, nausea (usually only when first started), and dry mouth.
  • Bupropion, brand named Wellbutrin, is a norepinephrine-dopamine re- uptake inhibitor (NDRI) that works by stimulating the POMC MC4R neurons of the hypothalamus, which can decrease food cravings and increase energy expenditure. It is now marketed as a combination drug along with naltrexone.

What Side Effects Do Anti-Obesity Medications Have?

Each of the anti-obesity medications has side effects, ranging from mild to serious. Several of these medications have been taken off the market due to serious adverse effects; for example, fen-phen in the United States, due to pulmonary hypertension and heart valve damage; rimonabant in the United Kingdom, due to its association with psychiatric disorders, including depression and suicidal tendencies; and sibutramine (used from 1997 through 2010, when the Sibutramine Cardiovascular Outcomes [SCOUT] trials showed an association with an increased risk of major cardiovascular events in patients with obesity as compared to those taking placebo). The drugs that have been removed from the market had a different mechanism of action than the medications that are currently FDA approved, so it is not logical to assume that all obesity drugs are dangerous. As always, it is necessary to be informed about the expected benefit of any medication you might consider taking as well as its risks and then determine whether it has a favorable risk–benefit ratio. There is a framework of stepped interventions based on body mass index (BMI) and co-morbid health issues to guide clinicians in the selection of treatment for patients with overweight and obesity, based on the guidelines of the National Heart, Lung and Blood Institute (NHLBI) in 1998. This is important because these medications are not used for those with normal BMIs (Bray and Ryan, 2014).

Following are some common and serious adverse medication effects of FDA-approved anti-obesity medications:

Liraglutide 3.0 mg (Saxenda)

Common side effects of liraglutide include nausea, diarrhea, constipation, headache, vomiting, low blood sugar (hypoglycemia), decreased appetite, upset stomach, fatigue, dizziness, stomach pain, and changes in enzyme (lipase) levels in your blood. There is a Black Box warning suggesting that it might induce thyroid cancers.

Lorcaserin (Belviq)

Common reactions include hypoglycemia (low blood sugar), headache, anemia, dizziness, nausea, vomiting, fatigue, hyperprolactinemia, diarrhea, dry skin, bradycardia, and cognitive impairment. Serious reactions include the risk of serotonin syndrome, pulmonary hypertension, valvular heart disease risk, bradycardia, and psychiatric disorders (including depression and thoughts of suicide).

Naltrexone/bupropion SR (Contrave)

Common reactions include nausea/vomiting, headaches, dizziness, insomnia, diarrhea, increased blood pressure and heart rate, anxiety, flushing, fatigue, tremor, ringing in the ears, and irritability. Serious adverse effects include neuropsychiatric symptoms, suicidality, Stevens-Johnson syndrome, severe hypertension, hepatotoxicity, and seizures.

Orlistat (Xenical—prescribed; Alli—over-the-counter)

Common reactions to orlistat include oily stool spotting, flatus with discharge, fecal urgency and incontinence, fatty stools, an increased number of stools, fatigue, dizziness, and rectal discomfort. Adverse effects that can be severe include fat-soluble vitamin deficiency, hepatotoxicity, nephrotoxicity, and oxalate nephropathy.

Phentermine/topiramate (Qsymia)

Common side effects include paresthesias (a burning or prickling sensation of your hands, feet, or other parts of the body), dry mouth, constipation, a metallic taste, insomnia, dizziness, headache, nausea, back pain, fatigue, diarrhea, blurred vision, depression, anxiety, attention disturbance, and cognitive impairment. Serious reactions can include severe metabolic acidosis

(a disturbance of the electrolytes in your blood), kidney stones, adverse effects on your bones (such as osteoporosis), increased body temperature, rapid heart rates, pulmonary hypertension, Stevens-Johnson syndrome, suicidal thinking, and seizure (if stopped abruptly).

For short-term use only (less than 12 weeks):

Phentermine (Lomaira/Adipex)

When first beginning phentermine/topiramate extended release (ER), the dose is titrated up over 14 days to improve its tolerability. Common side effects include palpitations, rapid heart rate, elevated blood pressure, restlessness, dizziness, insomnia, a change in mood, tremor, headache, dry mouth, an unpleasant taste, impotence, and a change in libido. Serious adverse events include cardiac ischemia (i.e., a condition in which the heart does not receive enough blood flow), elevated blood pressures and heart rates, pulmonary hypertension, psychosis, symptoms of dependency and withdrawal (if it is abruptly discontinued).

Phendimetrazine, benzphetamine, diethylpropion

Similar common and serious side effects as phentermine.

Following are common and serious adverse medication effects of off-label anti-obesity medications:

  • Metformin has several common side effects, including diarrhea, nausea, vomiting, abnormal weakness or a lack of energy, indigestion, decreased appetite, headache, a metallic taste, and rash. More serious adverse effects include lactic acidosis, megaloblastic anemia, and liver toxicity.
  • Topiramate has a long list of possible side effects, including metabolic acidosis, tingling of the extremities, sleepiness, dizziness, fatigue, nervousness, a lack of appetite, cognitive dysfunction, problems with balance, and ataxia, mood disturbances, and others. Serious adverse reactions can include severe metabolic acidosis, kidney stones, problems with bones (such as osteoporosis), hyperammonemic encephalopathy, psychosis, suicidal thinking, anemias, glaucoma, Stevens-Johnson syndrome, and withdrawal seizures (if abruptly discontinued).
  • Zonisamide can cause sleepiness, dizziness, nausea, headaches, irritability, agitation, fatigue, impaired concentration, impaired memory, confusion, depression, insomnia, double vision, speech disturbance, and diarrhea. Serious reactions include Stevens-Johnson syndrome, changes in your blood (e.g., aplastic anemia), hyperthermia and heat stroke, pancreatitis, depression, suicidality, psychosis, rhabdomyolosis, status epilepticus, and withdrawal seizures if abruptly discontinued.
  • Fluoxetine can cause insomnia, nervousness, nausea, headache, diarrhea, dry mouth, a decrease in libido, yawing, tremor, dizziness, and sweating. Serious reactions can include suicidal thinking, hypomania/mania, heart rhythm problems (such as torsades de pointes), serotonin syndrome, hyponatremia, and other adverse effects.
  • Bupropion commonly causes a dry mouth, headache, agitation, nausea, and dizziness. Some might experience tremor, sweating, abnormal dreams, insomnia, and ringing in the ears. Serious reactions include suicidal thinking, mania, homicidal ideation, seizures, severe hypertension, myocardial infarction, arrhythmias, Stevens-Johnson syndrome, and hepatotoxicity.

What Over-The-Counter Weight-Loss Medications Are Available and Should I Use Them?

For many reasons, only a small percentage of people with obesity who could benefit from prescribed medications to enhance weight loss ever receives a prescription. As noted earlier, this can be from a number of causes, including worry about side effects, a lack of knowledge of available options, the financial burden of expensive medications and surveillance, and the time it takes and sometimes the embarrassment of talking to a physician about treatment options. There is also a growing interest in complementary and alternative medicine (CAM). A quick search of the internet or a drug store aisle quickly reveals numerous “magic pills” available for purchase. This offers privacy and generally a lower price point to start treatment, but there are some very serious things to consider before beginning your own “natural” treatments.

Diet supplements, vitamins, minerals, herbal remedies, and nutraceuticals are considered dietary supplements and are not FDA approved. Therefore, the industry is largely unregulated and can make claims without scientific studies to back up their claims. The purity of the ingredients can be questionable, and it is possible that not all ingredients are listed accurately. Caffeine is sometimes added to increase the stimulant effect. One study found that 47% of the samples analyzed contained more than 400 mg of caffeine, above the safe limit; excess amounts of caffeine can lower your seizure threshold, cause palpitations, and increase your blood pressure (Neves and Caldas, 2017). The dose of the supplement is not necessarily correct, particularly given that there are seldom any quality clinical trials done to determine dose and efficacy.

“Natural” does not equal “safe.” Many of the herbs and nutraceuticals have very significant side effects on the heart and liver or can have interactions with medications you are currently taking. A common “natural” product we sometimes use is grapefruit juice, which can interfere with other medications, especially cholesterol and drugs to lower your blood pressure, which could lead to severe adverse effects. It is very important to discuss any supplement you are thinking about taking with your health-care provider. You can also do some research on your own via the internet at the National Center for Complementary and Integrative Health (https://nccih.nih.gov/). 

This is a government organization that provides unbiased information on alternative and complementary non-prescription medications, including reviews of clinical trials and safety information.

The American Association of Clinical Endocrinologists established medical guidelines for the clinical use of dietary supplements and nutraceuticals in 2003. Many studies of alternative dietary supplements and nutriceuticals (DS/N) were reviewed, and none were found to have demonstrated safety and efficacy by more than one peer-reviewed study. This is its statement:

“Because the principle of ‘do no harm’ cannot be guaranteed in light of (1) the multiplicity and complexity of DS/N-food-medication interactions and (2) the lack of sufficient scientific substantiation to outweigh potential risks, AACE cannot recommend the use of any DS/N or nonprescription product for obesity management (grade D).” 

Likewise, we cannot recommend any over-the-counter supplement for weight loss. Many have drug-like effects that are unpredictable and could be dangerous. Some are toxic in larger doses, and most have not been well studied. Here, we have chosen a few of the many dietary supplements on the market and discuss the purported benefits and known risks.

  • Garcinia cambogia is hydroxycitric acid that is extracted from dehydrated fruit rind, commonly used in cooking in Southern India. It works by preventing the activity of an enzyme in the body that lessens appetite. There are no side effects, based on the fact that it has been taken for centuries. Studies show a modest effect on weight loss in humans in short trials; that is, more than 12 weeks.
  • Camellia sinensis is a green tea produced from the C. sinensis plant that contains polyphenols that influence the sympathetic nervous system. This increases energy expenditure, which is the only effect that has been proven in studies to affect weight. There is very little evidence that is suppresses appetite.
  • Chromium picolinate is thought to boost glucose metabolism and affect the neurotransmitters that regulate food cravings and eating behaviors. There is not enough evidence found in a recent review (Esteghamati et al, 2015) to verify any claims of efficacy or safety of this product.
  • Hoodia gordonii is one of the most popular “natural” weight-loss products. It has been used in South Africa by the bushmen of the Kalahari Desert traditionally to suppress thirst and hunger during hunts. It was initially investigated by the South Africa Council for Scientific and Industrial Research, which licensed an agreement with a British pharmaceutical company, PhytoPharm, which then collaborated with Pfizer to study the extract. Pfizer ended its collaboration in 2003 due to difficulty with synthesizing the extract into a drug. Unilever then collaborated with PhytoPharm, but it ended the collaboration in 2008 saying that the extract could not meet expectations for safety and efficacy. There are very few scientific studies on Hoodia; nevertheless, it enjoys robust sales to unwary consumers (Misra, 2013).
  • Other over-the-counter products on the market are Hydroxycut, which contains caffeine and some herbs, caffeine, Raspberry Ketones, Green Coffee Bean Extract, Glucomannan, Meratrim, Green Tea Extract, Conjugated Linoleic Acid (CLA), Forskolin, Bitter Orange/Synephrine, Meltdown, One XS, F.A.S. Lean, Xtreme Lean, and numerous others. Most of these products have little or no safety or efficacy data for short- or long-term use, and they are not regulated by the FDA.

The quest for safe and effective medications to treat the chronic disease of obesity is an ongoing search. We now have several options to choose from, including medications that can be used long term, with at least some safety data. As we learn more about the complex signaling and feedback loops in our bodies, researchers can create other drugs that target some of the factors that lead to obesity. A healthy lifestyle will always be an essential part of any treatment of obesity. However, for some people with obesity, adding a medication to their regimen might help them achieve and maintain the health benefits of weight loss.

Should You Try Weight Loss Supplements?

Certainly, a person cannot rely on a single food or supplement to burn fat. They should also decrease their calorie intake and increase physical activity. However, when used as part of a healthy diet and lifestyle, natural fat burners may accelerate weight loss by either increasing metabolism or decreasing appetite.

Traditional approaches to weight loss cannot be substituted by natural supplements. That said, they may help people burn slightly more calories every day, gradually increasing weight loss.

Resurge is of the most popular weight loss supplements that promise to help you shed pounds and sleep better. Because studies have shown that sleep deprivation is associated with deficiencies of growth hormone and elevated levels of cortisol, both of which contribute to obesity.

While other supplements promote nutritional factors, meal replacement forms, appetite suppression, or similar effects, Resurge boosts your body’s metabolism by increasing your core temperature. However, before making any purchases, you might want to read some Resurge reviews because the supplement industry is rife with scams.

It should be noted that pills or supplements are usually not recommended for children, pregnant and breastfeeding women because some of their ingredients e.g. caffeine can have serious side effects when consumed in large amounts. For example, if a pregnant woman consumes over 200 mg of caffeine per day, her baby is at an increased risk of fetal growth restriction and/or miscarriage, though caffeine can boost your weight-loss efforts.

Although the formula of Resurge doesn’t have any stimulants, you should still talk with your doctor before you start taking the supplement, especially if you have health concerns.

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