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Genetic Obesity Management: FAQs
Expert Answers to FAQs About Genetic Obesity Management Across Syndromic and Monogenetic Obesity

Released: December 07, 2022

Expiration: December 06, 2023

Stephanie Sisley
Stephanie Sisley, MD
Fatima Cody Stanford
Fatima Cody Stanford, MD, MPH, MPA, MBA
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Key Takeaways

  • Testing for genetic causes of obesity can be offered to patients for free in the United States through a sponsored website.
  • Positive genetic tests may provide validation to patients who are struggling with genetic causes of obesity, even if no treatments are available.
  • It is essential to counsel patients on all available treatment options for genetic forms of obesity, including off-label treatments and clinical trials for which they may qualify.

In this commentary, Stephanie Sisley, MD, and Fatima Cody Stanford, MD, MPH, MPA, MBA, answer learners’ questions about the management of genetic forms of obesity from the live symposium “Advances in Genetic Obesity Management Across Syndromic and Monogenetic Obesity.”

Where do you typically send patients for genetic testing?

Fatima Cody Stanford, MD, MPH, MPA, MBA:
Free testing for genetic causes of obesity is available for anyone in the United States, and it is free for healthcare professionals to register. You can register at rhythm.preventiongenetics.com. 

I do this for my patients presenting with symptoms that lead me to believe they may have a genetic cause for their obesity. We need to test for these causes. Sometimes the results indicate POMC or PCSK1 deficiency, for which we have an approved treatment. Still, sometimes the results indicate an even more rare genetic cause of obesity, such as a heterozygote for which we don’t know what to do. But your patient may qualify for a clinical trial in your area, so I encourage you to look into that if no approved treatment is available.

When do you test for monogenic obesity in adults?

Fatima Cody Stanford, MD, MPH, MPA, MBA:
That an excellent question. When looking at adult patients, we must look at their whole history. Unfortunately, we only have a little time within a short office visit to do this thoroughly. But suppose we see a patient who has struggled with obesity, has tried many therapies, and has a history of early-onset obesity with significant hyperphagia. In that case, that may indicate there is something else going on. That is not a simple obesity presentation.

For example, one of the patients I referred to a clinical trial was a 32-year-old woman who struggled. She has had multiple forms of treatment—metabolic and bariatric surgery, sleeve, and gastric bypass. We have tried all forms of FDA-approved treatment—some for obesity and some not—and her response has been minimal at best. When we tested her, 5 positive results appeared in her genetic test, which reassured her and made her understand that she’s not just someone who has failed at these therapies—that the treatments failed her.

When you change that thought process and get people to understand that this isn’t about something they are doing wrong—this is about how their body is functioning—it really is helpful. She plans to enroll in a trial to get some answers, and I am hoping we see some positive results.

Another thing to note is that even if your patient has had a whole exome and it comes back negative, that does not mean you have ruled out all genetic forms of obesity, because you have no idea what gene is going to be discovered next year, which won’t show up on the current test. So, for patients with negative tests in the past, you may want to repeat the genetic testing because new things might have come up, and the repeat test may show something positive.

Does insurance approve glucagon-like peptide-1 (GLP-1) receptor agonists for use in patients with syndromic obesity?

Fatima Cody Stanford, MD, MPH, MPA, MBA:
Unfortunately, they do not get approved very often. The GLP-1 inhibitors are approved only for obesity, and there is no secondary indication for specific genetic forms of obesity. I live in Massachusetts, where we tend to have a more favorable environment with approvals. All of our employer-sponsored insurance in Massachusetts does cover these agents.

Now, we cannot get these medications approved when we are talking about patients with Medicare or Medicaid as their primary insurance. That is definitely frustrating for populations who tend to have high vulnerability and high rates of obesity at large, not just these genetic forms of obesity.

How do you counsel families about drugs that are off label?

Stephanie Sisley, MD:
I tell them FDA-approved options for treatment, but sometimes patients do not qualify for those treatments based on age. If there are no options, then I explain that we could use a drug off label, which means the FDA has not approved the drug in the way I want to use it or for this indication, but I want to use it for your child to help them with their weight gain. The most common treatment I use off label is an attention-deficit/hyperactivity disorder (ADHD) stimulant because it tends to be affordable for people. I make it very clear in my note, though, that I am doing it for hyperphagia, not ADHD. I also put in my note that I have discussed with the family that the recommended drug is not FDA-approved for obesity, and that the patient or patient’s family has agreed to the treatment. However, ADHD medications are controlled substances, so check your state law for prescribing guidance.

Fatima Cody Stanford, MD, MPH, MPA, MBA:
In addition to that, I often have used drugs such as topiramate. What we find is that topiramate is excellent for evening hunger. I dose the topiramate in the evening and discuss with the parents why we are using it. Unfortunately, in many of these situations we often deal with families with obesity. So, even if we are not dealing with the genetic and syndromic forms of obesity or are unsure of the cause, we know obesity is highly inheritable. If we have parents with obesity, there is a 50% to 80% likelihood that the child will have obesity. So, in my care of patients who range in age from 2-90 years, I often am caring for children, parents, grandparents, and—in certain situations—even great-grandparents. This helps build trust with patients and allows me to start other agents for patients as young as 2-3 years of age if they present 2 or 3 standard deviations above the growth chart with a strong family history of severe obesity but no genetic testing that confirms this is secondary to any known genetic causes.

Are there quantitative or semiquantitative instruments for the assessment of hyperphagia?

Stephanie Sisley, MD:
I do most of it clinically. I have my set questions, but if I use a questionnaire, I tend to use the Children’s Eating Behavior Questionnaire. I like it because there also is an adult version (Adult Eating Behavior Questionnaire, AEBQ). So, if I have an 18-year-old or a 19-year-old, I can switch to the adult version. It has multiple scales, and one is a food satiety scale. You also can pull specific questions from the questionnaire to use if needed.

Fatima Cody Stanford, MD, MPH, MPA, MBA:
Those are great resources and tools. Often the patients and family give you the answers you need on their own if you listen to them. They may say, “I have to lock the refrigerator” or “I place certain items out of reach.” These statements give you a sense that the patient has an insatiable desire to eat and consume.

Stephanie Sisley, MD:
One of my favorite questions to ask, especially for kids, is, “Do they have favorite foods?” I have parents who will say their kids are hungry all the time, but they eat only pizza, chicken nuggets, and French fries. To me, that is not hyperphagia. I do not doubt they are hungry, but the kids with true hyperphagia have never met a food they do not like. They will eat broccoli, salad, fruit, and anything in front of them.

How do you counsel patients who have heterozygous forms of obesity?

Fatima Cody Stanford, MD, MPH, MPA, MBA:
This is a challenging issue. Most of the genetic tests I have sent off come back with heterozygotes. There are no approved therapies for heterozygotes. Still, many heterozygotes often are more likely to respond to more traditional forms of treatment, whether it be metabolic and bariatric surgery, pharmacotherapy, or a combination. So that is important.

If we look at homozygotes for melanocortin 4, there are fewer than 20 documented case reports—one of which is mine—from around the world. They respond less to a heterozygote for melanocortin 4 than traditional therapies. So, I tell them we can try traditional medicines and see how effective they are.

Stephanie Sisley, MD:
Some data show that you have increased weight if you are heterozygous for POMC, PCSK1, or leptin receptor. Knowing that—even if no specific therapy is available—gives the patient validation that they are fighting against something real. It is not them being a failure, and it is not that they have made poor choices. Something physiologic is going on that is causing weight gain and obesity.

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