Steven R. Smith, MD


June 20, 2014

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Weight Loss: A Fundamental yet Elusive Goal

Hello. I'm Steven Smith from Winter Park, Florida, where I serve as Scientific Director at the Translational Research Institute for Metabolism and Diabetes and Professor at the Sanford-Burnham Medical Research Institute. I am at the American Diabetes Association (ADA) meeting now and wanted to talk about a few interesting topics that we have seen at the meeting around obesity.

I am often asked about obesity medications and why we need them. If people would just eat less and exercise more, everything would be fine. I certainly encourage and recommend for patients with or without diabetes who want to manage their weight to make sure that they do those things -- diet and exercise are critically important. But we all know intuitively that it is really hard. Even for many who do lose weight, sometimes they regain that weight, so it's a real challenge for them as well.

We have 2 approved drugs for the management of weight in patients with and without diabetes, and we have 2 more in the pipeline that I will tell you about. In terms of selecting patients who are right for weight-management drugs, it's important that they first try a lifestyle intervention program and seek help from a dietitian and/or exercise specialist. When those fail, in many patients it is time to move on and consider weight-management treatment with drugs.

The 2 drugs we have on the market right now are lorcaserin and phentermine/topiramate, a combination of 2 drugs. I'm not going to spend a lot of time on those today. Rather, since we are at the ADA meeting, new data have been presented on 2 new drugs that are in the US Food and Drug Administration (FDA) approval process. I want to spend a few minutes talking about those.

Weight-Management Drugs in the Pipeline

The first is a drug that diabetes specialists may be familiar with. It's called liraglutide, and it's a glucagon-like peptide-1 (GLP-1) receptor agonist that is used to treat patients with type 2 diabetes.

We already knew that some patients on the diabetes dose of liraglutide would lose some weight. That led the company, Novo Nordisk, to explore the idea that higher doses of liraglutide might be effective for weight management in patients with and without diabetes. Those data[1] are being presented here, many of the data sets for the first time, on the use of liraglutide for weight management.

The somewhat higher dose that is needed to treat body weight in individuals with obesity has been tested. Many of the pivotal trials are coming out. It looks very effective for treating obesity and has a very nice profile in terms of safety (which we knew from the diabetes studies) and also durability.

What do I mean by that? It's hard for some people to lose weight and easy for others. Once that weight is lost, durability is the ability to keep the weight off for extended periods of time. Liraglutide has been shown to have that durability in some of the early studies. So think about patients with diabetes who need to lose weight who may be at risk for needing more drugs to treat their diabetes, and consider a weight-loss approach.

The other medication that we have in the pipeline at the FDA is called naltrexone/bupropion.[2] These are 2 drugs you may already know about. Basic science studies showed that when they were combined, they produce additive, if not synergistic, effects on body weight reduction in animals.

Naltrexone is an opioid receptor antagonist. Bupropion is a drug that is used for smoking cessation and for depression. Together, they adjust the neurochemistry in the brain to reduce hunger and increase satiety -- and together in this formulation and in an extended-release formulation, they are being tested for obesity management as well.

Not for Everybody

Obesity drugs are not for everybody, and they are certainly not for cosmetic purposes. They do have a special place, we believe, in the management of patients with type 2 diabetes.

When we think about the ways that people develop diabetes -- type 2 diabetes in particular -- weight excess (overweight and obesity) are the primary drivers of our type 2 diabetes epidemic. We also know from many studies that weight reduction, whether it's through diet and lifestyle intervention (for example, exercise) or whether it is with medications such as those I have just mentioned, can help lower glycemic indices, such as the hemoglobin A1c level, and can particularly reduce postprandial excursions of glucose in patients with type 2 diabetes.

We have to pay careful attention to the side-effect profiles of these medications. There has been a lot of interest in and scrutiny of safety, but many of our weight-loss and weight-management drugs are associated with nausea. Some will have other adverse effects that we need to pay attention to, so I would encourage you to spend your time reading that prescribing information. Make sure you understand these medications, and use them properly.

The last thing I want to talk about in terms of weight management is how long and when we should use these medications. In the old days, we used such drugs as phentermine and other stimulant drugs for a short period of time. When we talk about weight management in the current era, we are talking about long-term use. The reason for that is that as soon as we stop weight-management drugs, the weight will come back.

Often, patients will come into the clinic, sit down, and say, "Doc, I don't feel like I need these medications anymore because I have been more physically active. I'm eating right." You might want to consider in some patients who are highly motivated and doing well with their lifestyle modification to make sure that they have that opportunity to come off the drugs, but in general these are medications that will help control glycemia and manage weight when taken long-term. Emerging safety data on these medications should make us feel more comfortable.

In addition, we need to think about other medications and adjusting those medications when we start patients on weight-management drugs, in part because if a patient who has diabetes is taking insulin, sulfonylureas, or other beta-cell secretagogues, the dosages of those may need to be reduced. We have to monitor blood glucose very carefully when people with diabetes start taking weight-management drugs.

So, be careful during the initiation phase, to make sure that you counsel and talk to your patients about this. Depending on their level of glycemic control, you may have to reduce some of these agents. Insulin and sulfonylureas are the 2 agents to pay particular attention to.

As we increase our armamentarium with medications to treat weight in persons with and without diabetes, we should all learn more, and the ADA is a great place to do that. There are some wonderful sessions here on these new medications and, broadly speaking, on weight management in patients with diabetes. Go and learn from the prescribing information and from other sources, and begin to think about how you might incorporate weight management into your diabetes practice or your general endocrine practice as a supplement to the other things that we know are so important, which are lifestyle modifications through diet and exercise.

From the ADA, this is Steven Smith, and it's been great talking to you.


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