Does it work?

We all know that obesity is on the rise across the country. This has led to many different trends related to losing weight. Unfortunately, all of them aren’t effective, and many aren’t safe. Recently, a new medication has been advertised as a specific treatment for obesity. Does it really work? Who is it for? What are other things to consider?

Close to 70% of American adults have obesity or overweight. Experts attribute this rise in weight over the past 40 years to increasingly processed foods and sedentary lifestyles. Obesity raises the risk of the leading causes of death, including heart disease, stroke, diabetes, Covid-19, and certain types of cancer. Studies show that losing 5% to 10% of body weight is associated with a reduced risk of cardiovascular disease. So, it’s no wonder that Americans spend $70 billion on weight loss products every year, including gym memberships, apps that count calories and track exercise, and premade diet meals and shakes. However, these traditional approaches make it easy to see where the current ideas about weight loss are failing dieters. When restricting food intake, the body fights the process through metabolic adaptation, which is thought to be an evolutionary defense against starvation. The result is that weight regain is far more likely.

One of the major problems is that most doctors and people with obesity still believe it’s just the person’s fault, and if they could just eat a little less, it would fix the problem. However, the medical community has said that obesity is a disease. The American Medical Association stated this almost a decade ago, and so did the National Institutes of Health. Research has shown that obesity is a complex metabolic disease with a clear biological basis. Starting in the 1980s and continuing into the 1990s, scientists discovered the hormones leptin (tells the brain how much fat the body has stored), ghrelin (stimulates hunger), and Glucagon-like peptide 1 (or GLP-1), which is the satiety hormone). These findings helped explain how much eating and weight gain are hard-wired and supported an earlier hypothesis that each person’s body has its own “set point” for weight. While you have to lift the fork, the drive to eat is physiologically regulated. So, even though successful weight loss is partly a function of behavior, genetics and environmental factors can make it extremely difficult for some people without outside help.

Realizing a potential market for weight loss medication, pharmaceutical companies started developing some. The first medication to be approved by the Food and Drug Administration (FDA) was phentermine in 1959. Since then, this area of drug development has had many instances of therapeutics being unable to demonstrate sufficient safety data to warrant approval or of adverse effects necessitating market withdrawal. In recent years, the primary focus has been on GLP-1. The hormone prompts the pancreas to release insulin after meals and decrease blood sugar. Two parts of the brain, the hypothalamus and hindbrain, explain why GLP-1 can aid weight loss. The hindbrain activates the hypothalamus, which helps control energy regulation, including eating. When GLP-1 reaches and binds to receptors in these areas, they release chemicals that tell other parts of the brain to stop eating. The problem with GLP-1 is that it doesn’t last long in the human body. Its natural half-life is only about 90 seconds. However, in the 1990s, researchers found that Gila monsters carry a similar, longer-lasting hormone in their venom. Using this data, drug companies began developing synthetic GLP-1s. In 2005 the FDA approved one to help control patients’ blood sugar levels with Type 2 diabetes. Besides phentermine, there are nine other FDA-approved anti-obesity medications, including diethylpropion, benzphetamine, phendimetrazine, orlistat, phentermine/topiramate ER (Qsymia), bupropion/naltrexone (Contrave), liraglutide (Saxenda), setmelanotide (Imcivree), and semaglutide (Wegovy). Other medications, like metformin or zonisamide, which are generally used for treating diabetes, are often prescribed “off label” and at the prescriber’s discretion to treat obesity.

Anti-Obesity Medications

Phentermine (Adipex or Suprenza) is an amphetamine that curbs your appetite. It’s approved for short-term use (a few weeks) because there’s a risk of becoming dependent upon the drug. Since it may cause insomnia, don’t take it in the evening.

Qsymia combines phentermine with the seizure/migraine drug topiramate. Topiramate produces weight loss in several ways, such as helping you feel full, making foods taste less appealing, and burning more calories. Since it has much lower amounts of phentermine and topiramate than when these drugs are given alone, you can take it long-term. According to the FDA, if you don’t lose at least 3% of your weight after taking Qsymia for 12 weeks, you stop taking it or increase your dose for the next 12 weeks. If that doesn’t work, you should gradually stop taking it.

Liraglutide (Saxenda) is a higher dose of the type 2 diabetes drug Victoza. It imitates an intestinal hormone that tells the brain your stomach is full. While it can be taken long-term, it’s unlikely to work for you if you don’t lose 4% of your weight after taking it for 16 weeks.

Naltrexone HCl and bupropion (Contrave) is a combination of drugs in an extended-release formula. Naltrexone is used to treat alcohol and opioid dependence. Bupropion is for depression, seasonal affective disorder, and smoking cessation. It can be used long-term. However, if you don’t lose 5% of your weight after 12 weeks, it’s unlikely to work.

Orlistat blocks your body from absorbing about a third of the fat you eat. The prescription-strength version is called Xenical. If you get it without a prescription, it’s called Alli (has half of Xenical’s dose). It’s vital to point out that you should be on a low-fat diet, meaning less than 30% of your daily calories come from fat. Also, it’s vital to take a multivitamin at least 2 hours before or after because the drug temporarily makes it harder for your body to absorb vitamins A, D, E, and K. You can take orlistat long-term.

In June 2021, the FDA approved Wegovy (semaglutide) for chronic weight management in adults with obesity or overweight (a body mass index, or BMI, over 27 kg/m2) with at least one weight-related condition (such as high blood pressure, type 2 diabetes, or high cholesterol) or a BMI of 30 kg/m2 or greater. It’s to be used in addition to a reduced-calorie diet and increased physical activity. Semaglutide is in a class of medications known as glucagon-like peptide-1 receptor agonists, or GLP-1 RAs, because it works by mimicking GLP-1. The drug was previously approved in 2017 under the brand names Rybelsus (oral) and Ozempic (lower-dose injection) to treat type 2 diabetes. Wegovy is given via injection, starting with a low dose of .25 milligrams a week and gradually working up to the target dose of 2.4 milligrams. The process takes about five months. The most common side effects are nausea, diarrhea, vomiting, and constipation. These usually subside after taking the medication for a while.

What’s the big deal with Wegovy?

Wegovy is the first drug approved for chronic weight management in adults with general obesity or overweight since 2014, and it’s the first GLP-1 RA medication to gain approval since 2005. It received significant media attention in the months preceding approval due to the widely reported STEP 1 trial results published in the New England Journal of Medicine. According to the data, participants had an average of 14.9% bodyweight reduction after 68 weeks of therapy in those assigned to the medication group, versus only 2.4% weight loss in those assigned to the placebo group. These outcomes are impressive because the average weight loss seen with existing anti-obesity medications is about 5% to 9%. Those who engage in lifestyle and behavioral therapy alone usually lose only 3% to 5% of their body weight. Wegovy’s performance suggests that anti-obesity medications could approach the 25% to 30% weight loss mark, which is huge since that has only been achieved with bariatric surgery. Since surgery is an invasive solution that permanently alters the digestive system, only 1% of those who qualify go through with the procedure. While medication treatment works more gradually, it’s definitely less invasive.

What’s the goal of anti-obesity medication?

The goal of anti-obesity medications is to reset “the set point,” which is the weight range the body tries to maintain. This point is elevated in obese and overweight individuals. If you restrict calories, your body thinks it’s starving, so it cues you to keep eating to maintain the elevated set point. Anti-obesity medications work in the brain to help bring that point down, enabling individuals not only to lose weight but also to maintain the weight loss.

It’s vital to point out that any of the drugs can take more than a year to reach full effectiveness. There needs to be a weight loss of 5% of total body weight in the first three months for any anti-obesity medication, which indicates whether the drug will continue to work. Also, individuals aren’t ‘cured’ once they lose weight. To continue maintaining weight loss, they need to continue taking anti-obesity medications. Research demonstrates that you gain the weight back when you stop the medication.

All anti-obesity medications are prescribed along with a lifestyle program. Key elements are consuming healthy food options, increasing physical activity, getting good quality sleep, and reducing stress. In addition, individuals need to keep in touch with a professional who can monitor their progress and tweak their program. One huge component of obesity treatment is therapy since the behavioral aspects of the condition can only be addressed through this. Several startups offer apps that can coordinate remote patient visits/coaching with doctors/dietitians and dispense prescriptions for regularly prescribed on- and off-label meds. They’re charging about $100 a month out of pocket for these remote services. It’s essential to note that none of these young outfits have released much data on outcomes, especially when it comes to long-term weight loss.

What are the challenges?

Many overweight people and all obese people are candidates for a prescription. However, less than 3% of qualifying Americans take weight loss medications. One of the significant challenges is the high cost of some newer therapeutics and the refusal of many private and public insurers to cover them. Insurers classify the drugs as lifestyle medications. If you have Medicare or Medicaid, there’s currently no coverage for anti-obesity medications. In 2012, the Treat and Reduce Obesity Act was a bill introduced to Congress. It was recently reintroduced in 2021. The goal is to amend the Medicare Social Security Act to authorize insurance coverage of obesity counseling services and FDA-approved anti-obesity medications.

Without coverage, patients aren’t left with many options. One is to pay out of pocket for a lower-cost generic anti-obesity medication. Another alternative is to take a medication primarily intended for treating other medical conditions that may also help with weight loss. The final choice is to have bariatric surgery, which is a more widely covered insurance benefit. However, the person’s BMI and health status must be severe enough to satisfy insurance requirements.

Considerable opposition to weight-loss drugs that must be overcome is the lack of buy-in from the community. In the 1990s, the drug combination fenfluramine/phentermine (or fen-phen) was pulled from the market after cases of heart damage in some patients. Since then, the public has seen obesity medications as risky. Despite numerous studies on GLP-1s showing no such concerns, many clinicians are hesitant to use them.

The Future

It’s undeniably bright when it comes to the future of anti-obesity medicines. Novo Nordisk, the maker of Wegovy, is working on a pill version. In addition, they’re focusing on a medication that combines Wegovy with an experimental drug, cagrilintide, which replicates another satiety hormone (amylin). The new treatment helped patients taking the highest dose lose an average of 17% of their body weight in an early-stage trial.

Pfizer is studying obesity treatments that could be derived from genetic data. Eli Lilly is perfecting an experimental drug, tirzepatide, which is a part of a new class of medicines that scientists think will replicate the effects of GLP-1 and another hormone, glucose-dependent insulinotropic polypeptide (GIP). So far, studies done in rodents indicate that GIP works together with GLP-1 better than GLP-1 alone.

In the fight against obesity, willpower is not enough! To help the greatest number of people, we need to change the misconceptions that people should be able to control the condition on their own. It’s vital to look at this as a medical issue and not a personal problem. Anti-obesity medications must be available to everyone who needs them. So, we must also address the lack of insurance coverage; otherwise, many patients will be left out. Given the current obesity health crisis we’re having, this is unacceptable.