I Prescribed a GLP-1. Now What?

Medscape

2 days ago

This transcript has been edited for clarity.
We've got another really important one today. We're going to discuss the new joint recommendations from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and the Obesity Society around nutrition and exercise for people prescribed GLP-1 therapy for obesity. This is a critically important area, as GLP-1 receptor agonists and the GLP-1/GIP dual agonist have become one of the most common medicines that we prescribe. These medicines are powerful and can lead to 15% to 22% weight loss with semaglutide and tirzepatide, respectively. A level of weight loss that I'll venture to say we did not imagine could have been possible just a few years ago.
But as Spider-Man once famously said, 'With great power comes great responsibility.' We need to make sure we're spending the time that it takes to give proper advice to patients about nutrition and exercise if we want our patients to achieve the optimal health outcomes that they can get from this class of medicines. GLP-1 receptor agonists and the GLP-1/GIP dual agonist have absolutely changed the landscape for treating overweight and obesity but also come with powerful side effects, both short- and long-term.
On the good side, these medicines are clearly metabolically healthy. They lead to a decrease in LDL cholesterol and triglycerides, improvement in HDL cholesterol, decreased blood pressure and blood sugar, as well as decreased vascular events in those with existent ASCVD and even improvement in arthritis pain, resolution of obstructive sleep apnea (in half of the people with OSA and obesity that were studied in an important study), and improvement in fibrosis in MASH. Nonetheless, the GLP-1s need to be used carefully and our advice is critically important if the promise of these medicines is to be fulfilled.
Prior to starting weight-loss medicines, a comprehensive weight history should be taken, including asking about identifiable influences to gaining weight. We also need to look for evidence of eating disorders, which would affect the decision of whether to start an appetite-suppressing medicine, as well as influence the way that we're going to monitor people once they're on it. In addition, we should ask about mood disorders because weight loss can either exacerbate or improve depression. Finally, ask about risk of sarcopenia and assess for risk of sarcopenia, which is more common with increasing age, chronic illness, and sedentary lifestyles.
Let me now discuss symptomatic side effects. First, after starting a GLP-1 receptor agonist, about a third of people during the first 1-3 months will have some degree of nausea, vomiting, diarrhea, or constipation, which are usually described as mild to moderate in degree. In order to mitigate those GI side effects, we can remind people of a few tricks.
Eat small meals frequently rather than just one or two large meals a day. Avoid greasy or fatty foods. Practice mindful eating — always has been important, still is. Things like eating slowly and making sure to stop eating when you begin to feel full.
In addition, it's important to remind people to consciously stay hydrated because along with suppression of appetite, there can be alterations in thirst mechanism, which is particularly important this time of year. For people who are experiencing a lot of GI side effects, a slower dose titration can be helpful. If nausea is a challenging issue, antinausea medicines, such as prochlorperazine or ondansetron, can be prescribed to help people get through the first few months. If constipation is an issue, increasing fluids and fiber can be encouraged and medications such as polyethylene glycol can be used.
Let's move on, now, to potential for nutritional deficiencies. When you decrease the amount you eat substantially, you can decrease the amount of vitamins and minerals that you get. Advise patients to eat nutrient-dense, minimally processed foods, including fruits, vegetables, whole grains, legumes, lean proteins, nuts, and seeds. Supplementation can be considered for at-risk nutrients, such as vitamin D, calcium, and B 12 — or just recommend a multivitamin with minerals.
Preservation of muscle and bone is critical. Rapid weight loss can lead to loss of both fat and lean body mass (that is, muscle mass). About a quarter of all the weight that is lost on GLP-1s comes from muscle. It is not the medicines, though, that caused the loss of muscle. It's the rapid weight loss. That same thing happens with a very low-calorie diet, bariatric surgery, or medications. To mitigate the loss of lean body mass, two things are important. The first thing is nutrition. The second thing is exercise.
When you're in a calorie deficit, your body needs to get sufficient amino acids to preserve and build muscle mass. While the recommended daily allowance for protein in adults is 0.8 g/kg/d, when someone is at a significant calorie deficit, a higher intake of protein is recommended. There's not clarity in the literature as to the correct amount of protein. Some recommendations actually go up to 1.2-1.6 g/kg/d during active weight reduction. Some experts recommend protein needs to be calculated based on total weight; others recommend based on lean body weight. There's a lack of clarity here.
As a reasonable compromise to these varied recommendations, I usually recommend that patients take in about 0.4-0.5 grams of protein per pound of body weight during weight loss. This means that a roughly 200-pound individual should aim to get about 70 or 80 grams of protein daily. Don't fret over the exact amount, but just make sure that you're not way undershooting the right amount.
The reality here is that this often requires planning in order to achieve adequate protein intake. I usually recommend to patients that they can try a protein shake in the morning to help them achieve their protein goals. The advisory emphasizes that lower-volume nutrient-dense protein foods can be encouraged. Things like fish, eggs, Greek yogurt, cottage cheese, nuts and seeds, chicken. I want to emphasize that protein alone, though, is not going to be enough to help preserve muscle mass. You need to do resistance exercises, as well.
As for bone health, the relationship between GLP-1 use and bone density is complex and unclear. There's some evidence that GLP-1s may actually protect bone density, while it is clear, though, that rapid weight loss leads to a loss of bone density. What is clear is that exercise is critical for the preservation of both lean body mass — meaning muscle — and bone density.
So, putting it all together: When GLP-1s or dual agonists are prescribed, in order to have optimal outcomes, they should be prescribed with an exercise program, aiming for strength training at least three times weekly, plus at least 150 minutes of moderate-intensity aerobic exercise weekly, as well, to preserve muscle and bone mass.
This is not easy. I'm not saying it is. I am saying it's important. A dietitian can help with nutrition, and a personal trainer or YouTube videos are also resources for learning how to do strength training — that is, resistance exercises.
Finally, for a variety of reasons, people often stop taking GLP-1s. It's clear that most people will put weight back on. Maybe not everyone and maybe not all of the weight — that's going to depend on how you approach these lifestyle issues. When you gain weight back, unless you're exercising you will not gain back muscle that has been lost. And muscle is important for health. It's important to utilize the time on the medications to reinforce healthy habits, healthy food choices, and regular exercise, because doing so increases the likelihood of success in keeping at least some of the weight off and diminishes the loss of bone and muscle over time.
These are powerful medicines. And to make the best use of them, and for patients to achieve the best outcomes, requires input from us, as clinicians, for a significant commitment on the part of patients to do the work, as long as we provide the knowledge in order to achieve those outcomes.
I'm interested in your thoughts. For Medscape, I'm Dr Neil Skolnik.