New Weight-Loss Drugs
How new antiobesity drugs can be part of diabetes management
Unlike a rash or an earache, obesity is not a problem that can be fixed with a short course of treatment. Just as there is no cure for diabetes, there is no cure for obesity.
“And if you think of it that way, then you really think about long-term management,” says Robert Kushner, MD, professor of medicine at the Northwestern University Feinberg School of Medicine in Chicago.
About 35 percent of adults in the United States are considered obese, and 69 percent are either overweight or obese. The terms “overweight” and “obese” define ranges of weight greater than what is thought to be healthy for a given height. They also identify weight ranges that could increase the likelihood of certain health problems, such as type 2 diabetes and heart disease. Weight ranges are determined based on body mass index, a ratio of height to weight. According to the Centers for Disease Control and Prevention, an adult with a BMI between 25 and 29.9 is overweight, and an adult with a BMI greater than 30 is considered obese.
There are three new drugs that may aid in obesity management: the recently approved weight-loss medications lorcaserin (Belviq), phentermine and topiramate (Qsymia), and naltrexone and bupropion (Contrave). All three kick-start and maintain weight loss, which can also help improve blood glucose levels in overweight and obese individuals with prediabetes and type 2 diabetes.
The three medications have been shown to improve A1C levels of people with type 2 diabetes in clinical trials, says W. Timothy Garvey, MD, professor of medicine and chair of the Department of Nutritional Sciences at the University of Alabama at Birmingham. “In each case, [the medication] led to the lowering of the hemoglobin A1C, and at the same time there was decreased need for conventional diabetes medication,” he says.
The weight-loss meds were also associated with a decrease in blood pressure and an improvement in abnormal lipids (blood fats such as cholesterol), an amazing result for people with type 2 diabetes, Garvey says.
Although these drugs all suppress appetite—by blunting feelings of hunger—to induce weight loss, they use completely different mechanisms, says Louis Aronne, MD, FACP, director of the Comprehensive Weight Control Center at Weill Cornell Medical College, vice chairman of the American Board of Obesity, and author of The Skinny: On Losing Weight Without Being Hungry.
Belviq works by targeting a hunger receptor, or serotonin receptor, in the brain and helps you feel full sooner, which reduces food intake and causes weight loss.
Qsymia is a combination of two medications that have been around for a long time and work in two different ways, though the exact mechanism is unknown. They have been shown to produce greater weight loss together than when used alone, Aronne says.
Contrave is a combination of a drug used for the treatment of alcoholism and another one used for depression and smoking cessation. Although researchers don’t know exactly how the medication works, scientists think that each drug acts on two areas of the brain involved in regulating how much food you eat. Individually, these medications produce a small amount of weight loss, says Aronne, but when taken together, weight loss doubles.
There are a couple ways to think about suppressing appetite, particularly in people who are obese, says Aronne. One is to reduce cravings, and the other is to create a greater sense of fullness. “We see people who have no sense of fullness,” he says. “They may not be thinking about food, but they just keep eating because they never really feel full.” Both of those issues can be addressed by taking these medications, he says.
Weight Loss Link
In light of these new drugs, it’s important to understand why weight loss is an essential part of managing type 2 diabetes in people who are overweight and obese. Multiple studies have shown that modest weight loss, a drop of between 3 and 7 percent of body weight, will improve diabetes control, says Kushner. And as you lose body weight, the insulin resistance found in type 2 is reduced, so your body is able to take glucose out of the blood more easily.
Other lifestyle factors are also at play, which is why all three weight-loss drugs must be prescribed in combination with changes to diet and exercise. “Hopefully you are also reducing simple carbohydrates, so you have less glucose that you’re taking in for your diet,” Kushner says. Also, as you increase physical activity “your body is able to more readily take sugar out of the blood stream for your active muscles,” he says.
One thing to keep in mind is that weight loss will be modest when taking one of these drugs. People may not reach an ideal body weight or see the exact cosmetic change they want, but it will make a big difference in their metabolism and diabetes, says Garvey. “These medicines produce between 5 to 10 percent loss in body weight, on average, in people with diabetes, and it’s always over and above whatever the lifestyle intervention does by itself,” he says. “It’s huge in terms of benefits that the patients accrue in terms of their metabolism.”
Before you get started with one of these prescriptions, your health care provider may want to discuss realistic weight-loss goals. “By talking about this modest weight loss, you’re hopefully going to prevent the unrealistic expectation that someone is going to lose an enormous amount of body weight, only to be disappointed.”
Aside from that, both Garvey and Kushner agree that modest weight loss is enough to make a big difference in the management of type 2 diabetes. It’s also possible that certain people will respond much better to these medications, which could produce more dramatic weight loss, says Aronne.
The indications for use, as defined by the Food and Drug Administration (FDA), are the same for all obesity drugs, including these three. Restrictions aim to weed out people who are looking to lose a few pounds and to ensure those who get the medication really need it. Anyone with a BMI of 30 or above and anyone with a BMI between 27 and 29.9 who has an obesity-related complication—such as diabetes, high blood pressure, or abnormal cholesterol—qualifies.
Garvey says that people who are at high risk for developing diabetes—such as those with impaired fasting glucose, impaired glucose tolerance, and metabolic syndrome—should be considered, too.
The tricky part is finding the right medication for each individual.
Side Effects May Vary
If given according to the prescribing instructions, these weight-loss medications are generally safe for use—the FDA wouldn’t have approved them otherwise. But some experts still have concerns. “The long-term cardiovascular safety is unknown,” says Adam Tsai, MD, MSCE, chair of public affairs for the Obesity Society and an internal medicine and weight management physician with Kaiser Permanente in Denver. “I think there have been some failures in the past with pharmacotherapy and safety, and so I think there are at least some theoretical safety concerns.”
Despite that, Tsai says that since Contrave and Qsymia are combinations of drugs that have been around a while, they are probably safe. That doesn’t mean they’re free of side effects, though. The most common side effects for Belviq and Contrave include nausea, dizziness, and headache, and all three come with some risk of psychiatric reactions, such as anxiety and memory problems. Qsymia has the benefit of significant blood pressure improvement.
You and your provider should have a conversation about side effects and contraindications (interactions with your other medications) and current medical problems, when choosing a weight loss drug.
The Price Is Right
The last factor to consider is cost. “They are all fairly costly,” Kushner says, “and it depends on your health plan coverage.” The average out-of-pocket cost for Qsymia and Belviq is between $180 and $210 a month, and many health insurance companies do not yet cover antiobesity drugs. Contrave is around the same price out of pocket, but the manufacturer offers a savings program that can cut the cost to $45 after the third consecutive month of prescription refills, depending on insurance coverage. Anyone who qualifies for the program, even if they do not have insurance, will pay no more than $70, according to a Takeda representative.
However, Kushner says some plans are allowing patients to get the medications as long as they seek approval from their insurance company first. This would reduce the cost, but would likely still require a higher co-pay.
“If you are paying out of pocket, they are really expensive,” says Kushner, “and that may prohibit many individuals’ ability to afford these medications.”
The Problem With Lows
One problem that can occur when taking antiobesity drugs in conjunction with blood glucose–lowering medications—such as insulin and two classes of drugs, called sulfonylureas and meglitinides, which stimulate the release of insulin—is hypoglycemia. “We usually decrease these medications up front when we put them on one of these weight loss medications,” says Garvey, because people become more sensitive to insulin.
Aronne says reduction of diabetes medication and close follow-up is key, and he would prefer to err on the side of letting someone’s glucose run a little higher at first. If for some reason diabetes medications were not initially reduced, Kushner says he’d insist that the individual monitor his or her blood glucose very carefully and anticipate that it will be lower
In the past, Garvey says weight loss was not emphasized as a primary indication for the use of medications because safe and effective drugs weren’t available. “We have three new medications, and perhaps a fourth [Saxenda, below] on the way, and the weight loss indication increases our options for [diabetes] therapy,” he says.
There are two classes of newer diabetes drugs that also promote modest weight loss: GLP-1 agonists and SGLT-2 inhibitors. GLP-1 agonists, such as exenatide (Byetta) and liraglutide (Victoza), act as mimics to a particular hormone in the body that signals the pancreas to produce more insulin after you eat. It may help you feel full sooner, which could cause you to eat less and lose weight.
SGLT-2 inhibitors, such as canagliflozin (Invokana) and dapagliflozin (Farxiga), act on the kidneys, sending excess glucose, and therefore calories, into the urine, which promotes weight loss. “I think the advantage [of using these drugs] is that you can treat two conditions at the same time,” says Tsai.
A New Approach
Garvey says we now have tools that can prevent or delay the progression to type 2 diabetes in overweight and obese people. “We are in the middle of a diabetes epidemic,” he says. “The only way we’re going to deal with [the] diabetes epidemic is to prevent it.”
This mentality has laid the groundwork for a new specialty called “obesity medicine,” which recognizes obesity as a disease and sees specialists working as a team with cardiologists and endocrinologists. And, because obesity drives many other conditions and diseases—including diabetes—it makes more sense to treat weight first than to wait for complications to develop before improving health. “The time has come to manage the obesity,” Aronne says. “This is the approach we are beginning to see.”
New Antiobesity Drugs
Brand Name: Belviq
Drug Name: Lorcaserin HCI
Dosage: One 10-milligram tablet twice daily
Companies: Eisai Inc. and Arena Pharmaceuticals Inc.
Status: FDA approved in 2012
Common Side Effects: Headache, dizziness, fatigue, nausea, dry mouth, constipation, cough, and back pain
Brand Name: Contrave
Drug Name: Naltrexone HCI and bupropion HCI
Dosage: Tablet with 8 milligrams of naltrexone HCI and 90 milligrams of bupropion HCI once daily for the first week, twice daily for the second week, three times daily for the third week, and four times daily for the fourth week and beyond.
Companies: Orexigen Therapeutics Inc. and Takeda Pharmaceuticals USA Inc.
Status: FDA approved in 2014—with a requirement that the company conduct post-marketing trials on the drug’s effect on the heart, two looking at pediatric patients and another one evaluating the interaction between Contrave and other drugs. In March 2015, the LIGHT trial was halted partway through after Takeda released incomplete data. For now, the cardiovascular risks and benefits of Contrave remain inconclusive. A new trial will start this year and end in 2022, says Steven Nissen, MD, chairman of the Robert and Suzanne Tomsich Department of Cardiovascular Medicine at the Cleveland Clinic’s Sydell and Arnold Miller Family Heart & Vascular Institute and lead investigator for the study. Nissen will serve as study chairman for the new trial.
Common Side Effects: Nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea
Brand Name: Qsymia
Drug Name: Phentermine and extended-release topiramate
Dosage: Capsule with 3.75 milligrams of phentermine and 23 milligrams of topiramate daily for 14 days. After that, capsule with 7.5 milligrams of phentermine and 46 milligrams of topiramate daily
Companies: Vivus Inc.
Status: FDA approved in 2012
Common Side Effects: Dizziness, insomnia, loss of taste, constipation, dry mouth, and numbness or tingling in the hands, arms, feet, and face
Brand Name: Saxenda
Drug Name: Liraglutide
Dosage: 3 milligrams daily
Companies: Novo Nordisk
Status: FDA approved in December 2014
Common Side Effects: Nausea, diarrhea, constipation, vomiting, low blood sugar and decreased appetite
Robert Kushner, MD, is on the advisory board for Vivus (Qsymia) and Takeda Pharmaceuticals (Contrave) and is a consultant for Eisai (Belvia). W. Timothy Garvey, MD, is a consultant for the pharmaceutical companies Vivus, Eisai, Takeda Pharmaceuticals, and Novo Nordisk (Saxenda). He is principal investigator for Eisai. Louis Aronne, MD, has received research support from Novo Nordisk. He serves as a consultant and advisor for Novo Nordisk, Eisai, and Vivus.