GLP-1 Medical Therapy: The Game Changer for Weight Loss and Cardiometabolic Health
This article is provided for informational and educational purposes only, and does not intend to substitute professional medical advice, diagnosis, or treatment.
Let’s start out this discussion first with the most important point: we must approach our patients struggling with overweight and obesity with incredible empathy and compassion — and understand that there is NO one size fits all approach for nutrition, diet, exercise, and weight loss. Often our patients blame themselves, and believe they have failed a certain diet program, when in reality, it’s the diet program that has failed our patients. Not every dietary intervention and weight loss program is going to be suitable for every patient. Obesity is a complex disease, with a complex interplay between genetics, food environment, neurohormonal and various other factors that make treating obesity complex. Shaming patients who are overweight or obese has NO place anywhere in medical care, or elsewhere. The old adage of “pull yourself up by your bootstraps” as a weight loss approach, telling people to just “eat right” and “exercise more”, does not help many patients struggling with weight, and does not align with the scientific evidence as a solution for everyone with obesity.
As a cardiologist who cares deeply about lifestyle change, including nutrition, and exercise, I believe strongly that the false dichotomy of lifestyle change vs medications need not exist. This false dichotomy only harms our patients. We now have many tools to help our patients with obesity. That is why we must discuss the game changer in obesity medical management: GLP1 receptor agonists. (You may know this as semaglutide, otherwise known as Wegovy, or Ozempic)
I want to dive into this first with stating that since Wegovy FDA approval for weight loss in 2021, I have been prescribing it to my patients with PHENOMENAL success. And it is important to reiterate: I have ZERO financial relationship or involvement with the company that makes it. (FYI — because of the Sunshine Act, every physician in the US has ALL financial relationships (and lack-thereof) with pharmaceutical companies publicly available for you to see. You can check the Sunshine Act Database through CMS online and see for yourself that I have taken zero dollars from Pharma!)
As a cardiologist, I frequently use Wegovy (Semaglutide 2.4 mg) with my patients who are overweight, or obese, who desire weight loss and have been struggling with diet and exercise alone — for a few reasons:
1. The incredible evidence-based data showing:
- Unbelievable weight loss: 16.7% weight loss at 2 years! Nothing comes close to this outside of bariatric surgery. Most other weight loss medications AND dietary interventions peak at about 5%, so to say this is a groundbreaking medication is an understatement.
- The incredible reduction in cardiovascular risk factors: improvement in blood pressure, inflammatory markers, fasting glucose and insulin, and triglycerides
- The impressive 2-year safety data results from STEP 5, which support a favorable benefit-risk profile of semaglutide 2.4 mg for long-term weight management in people with overweight or obesity.
2. Anecdotally: I have witnessed SO MANY of my patients, who have had a lifetime of struggling with their weight, finally feel free. Free of fad diets. Free of the anxiety around planning their meals. Free of trying to manage their appetite, and fighting insatiable hunger. The BEST part about this medical therapy, is seeing my patient’s quality of life improve. Seeing them feeling happier, more energized, more hopeful. Seeing them achieve their weight loss and cardiometabolic health goals without struggling. So many of my patients have told me that this medication, through mediating their appetite and satiety, actually helps them choose healthier foods, it helps them eat more fruits, vegetable, legumes, and reduces their cravings for tasty, hyperpalatable processed foods. They feel more confident in their exercise programs, can exercise longer, with less pain and less limitations!
So many of my patients have said this medication has provided them peace of mind. It made me realize that obesity is far more complex than many physicians, dietitians, and health coaches have ever given credit for. It made me realize, that for the right patient, this medication is literally life changing, and helps them to make all of the diet and lifestyle changes they have been fighting to achieve for so long.
The bottom line is: obesity is a complex disease which requires respect from physicians and non physicians: who should understand that patients deserve ALL of the tools we can offer them.
So now… lets dig into the science!
First, why is this an important discussion? Obesity is a common, serious, multifactorial disease. Obesity is the direct result of excessive fat depositions acquired due to a sustained imbalance in energy expenditure and energy consumption (Lam and Ravisson, 2016). Obesity is thus the direct result of the continuous consumption of excessive calories in the absence of the proportionate energy expenditure. Consequentially, the excess energy consumed is stored in the form of white adipose tissue. The body mass index (BMI) is the most commonly utilized way to assess a patient’s weight in context with their height. Although not the most perfect scale, with many caveats, it is the most cost efficient evaluation, in addition to using waist circumference and waist-to-hip ratio. (And before you yell about how terrible BMI is, not every patient can afford, or is interested in, obtaining a Dexa scan to evaluate their adiposity!)
According to the BMI scale, the average adult is considered to be within a healthy range with a BMI of 18.5kg/m2 to 24.9kg/m2. A patient is considered to be overweight with a BMI between 25kg/m2 and 29.9kg/m2 and is considered obese between a BMI of 30kg/m2 and 39.9kg/m2. A patient with a BMI over 40kg/m2 is considered severely obese. Central obesity is most commonly assessed via waist circumference (WC) and waist-to-hip ratio (Spreckley, 2018).
According to the CDC, the US obesity prevalence was 41.9% in 2017 — March 2020. From 1999 –2000 through 2017 –March 2020, US obesity prevalence increased from 30.5% to 41.9%. During the same time, the prevalence of severe obesity increased from 4.7% to 9.2%. Obesity-related conditions include heart disease, stroke, type 2 diabetes and certain types of cancer. These are among the leading causes of preventable, premature death. Although overall cancer rates in the US are decreasing, according to the Obesity Society, cancers that are linked to overweight are on the rise, including: Breast cancer • Colon cancer • Endometrium and uterus cancer • Esophageal cancer • Gallbladder cancer • Kidney cancer • Pancreatic cancer • Prostate cancer • Thyroid cancer • Head and neck cancers.
But, as time goes on, and our understanding of obesity and metabolic health advance, we are learning that obesity and weight loss are far more complex, nuanced, and multifactorial than previously thought. Losing weight is not as simple as “eat less, exercise more.” Many individuals have tried numerous dietary and exercise interventions to lose weight, only to be met with incredible frustration, as weight loss continues to be difficult for them to achieve, and maintain.
What is GLP-1?
Glucagon like peptide-1 (GLP-1) is a 30 or 31 amino acid long peptide hormone mainly secreted by 3 tissues in the human body: enteroendocrine L cells in the distal intestine, alpha cells in the pancreas, and the central nervous system. Through its interaction with the GLP-1 receptor (GLP-1R), GLP-1 participates in the regulation of glucose homeostasis. Initially, when GLP-1 receptor agonists (GLP-1RAs) were studied for treatment of diabetes, this was the main focus. Although the pancreas is the main target organ for the action of GLP-1RAs in diabetes treatment, it turns out they do SO much more. GLP-1 is likely best described as a neuropeptide with physiologically and pharmacologically relevant effects on food intake and body weight, and potential neuromodulatory roles. Research has found that the GLP-1R is most abundantly expressed in the hypothalamus, the brain stem and the septal nucleus, where mRNA expression is also seen! Food calories trigger the release of GLP-1 in both the gut and brain. GLP-1 decreases gastric emptying and intestinal motility and contributes to the ileal break, an inhibitory feedback mechanism that functions to optimize nutrient digestion and absorption.
So…what does the research show us?
First: a once-weekly subcutaneous injection of semaglutide 1.0 mg (Ozempic), a glucagon-like peptide 1 analogue, was approved for the treatment of type 2 diabetes, and has proven to reduce the risk of cardiovascular events in people with type 2 diabetes and cardiovascular disease.
Then following this, the ground breaking STEP 1 Trial, demonstrated that a higher dose of semaglutide, 2.4 mg (now known as Wegovy) could result in unbelievable weight loss and improvements in cardiometabolic health. This randomized, double blind trial, evaluated participants with overweight or obesity, without diabetes, and randomized them to 2.4 mg of semaglutide, a GLP-1 receptor agonist, once weekly + lifestyle intervention, or placebo + lifestyle intervention.
The individuals on semaglutide had almost 15% weight loss in 68 weeks, compared to just 2.4% weight loss in the placebo group!
In June 2021, this groundbreaking medication Wegovy was approved by the FDA for weight management in adults with obesity or overweight with ≥1 weight-related comorbidity (such as hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease.)
Then the question remained, what happens after 68 weeks? This question was investigated in the STEP 5 trial.
STEP 5 Trial
A 104-week trial (the longest duration trial of the STEP program) which investigated the long-term effect of semaglutide 2.4 mg compared with placebo on body weight and cardiometabolic risk factors in adults with overweight or obesity.
Who was studied?
Adults (≥18 years) with overweight or obesity
• BMI ≥30 kg/m2 *OR* BMI ≥27 kg/m2 with ≥1 weight-related comorbidity (hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease)
• This trial was for patients without type 2 diabetes
Objective of the 2 year trial:
• To compare the 2-year effect of semaglutide 2.4 mg once weekly, vs placebo, on body weight, cardiovascular risk factors, and glucose metabolism.
• To compare the 2-year safety and tolerability of semaglutide 2.4 mg once weely, vs placebo.
What did they find?
At 2 years, individuals who were adherent taking their semaglutide 2.4 mg once weekly (wegovy) lost 16.7% of their body weight, and sustained this weight loss!
At 2 years, 83.3% individuals who were adherent taking their semaglutide 2.4 mg once weekly (Wegovy) maintained greater than 5% weight loss.
But even more impressive:
56.8% of individuals maintained GREATER than 15% weight loss, and almost 40% of individuals maintained greater than 20% weight loss!
Let’s be clear: no medication, no diet or exercise program, to date, has ever demonstrated this result. Outside of bariatric surgery, this is the most effective weight loss intervention to date!
This is life changing for our patients!
What about cardiovascular risk factors? As a cardiologist — to me, this is by far the most important finding of this study!
Patients on semaglutide at 2 years, significantly decreased their cardiovascular risk! They significantly decreased their waist circumference, their blood pressure, and their inflammatory markers. So impressive!
Patients on semaglutide at 2 years, significantly improved their metabolic health. They improved their HgbA1c, their fasting plasma glucose and serum insulin, and their triglycerides!
Many patients on semaglutide at 2 years, significantly reduced their risk of developing Type 2 Diabetes! Participants with prediabetes at baseline dropped from 50.7% to 20.3% at the end of the trial!
Additionally, the 2 year trial provided not only robust data on semaglutide efficacy, but also safety. No new safety signals with semaglutide 2.4 mg were identified at 2 years! Safety and tolerability were consistent with the GLP-1RA class in general, which have been used safely and on the market for >16 years (since 2005).
What are the most common side effects? During the Step 1 trial, similar percentages of participants in the semaglutide and placebo groups reported side effects(89.7% and 86.4%, respectively). Gastrointestinal disorders (typically nausea, diarrhea, vomiting, and constipation) were the most frequently reported events and occurred in more participants receiving semaglutide than those receiving placebo (74.2% vs. 47.9%). Most gastrointestinal events were mild-to-moderate in severity, were transient, and resolved without permanent discontinuation of the regimen.
How can we reduce side effects? First of all — many patients go through the dose adjustment period in months 1–4 with no side effects, and breeze through with ease. But for those who do experience side effects, in my own anecdotal experience treating patients for weight loss with Wegovy over the last year, I have found some methods that have really helped to reduce side effects during the dose adjustment phase (months 1–4).
- Since semaglutide slows gastric emptying, if patients experience nausea, acid reflux, or GI upset, my patients often improve with reducing meal size, and increasing meal frequency. Most of my patients have found improvement in GI side effects by eating several smaller meals throughout the day, rather than eating the larger size meals that they were previously accustomed to.
- Increase dietary fiber intake, and encourage adequate hydration, to help reduce the chance of developing constipation. Most patients can tolerate increasing their fiber intake by 3-5 grams per day. Slow, but steady!
- Frequent follow up and support: we see our weight loss patients on semaglutide every 4 weeks before dose adjustment. We take side effects seriously, even though they generally are mild, and we monitor all patients closely during the first 4 months of medical therapy.
For full Wegovy safety data — click here
Results from STEP 5 support a favorable benefit-risk profile of semaglutide 2.4 mg for long-term weight management in people with overweight or obesity.
As a cardiologist who cares deeply about prevention, I am thrilled to have a medication that helps my patients achieve their weight loss goals, while reducing their risk for type 2 diabetes, and improving their cardiovascular risk factors.
I will always continue to emphasize to all of my patients the importance of eating a healthful diet, as nutrition and exercise are both incredibly important in cardiovascular disease prevention. But for the right patient — this once a week injection can be a game changer, not only for weight loss, but it can help empower our patients to make the lifestyle changes that will reduce their risk for developing chronic disease.
Dr. Danielle Belardo is a preventive cardiologist in Los Angeles, California, who helps patients across the United States & internationally, to optimize their weight and cardiovascular health through her practice Precision Preventive Cardiology. Dr. Belardo sees patients for cardiovascular disease, preventive cardiology, advanced lipidology, hypertension, cardiometabolic health, and weight loss. Dr. Belardo and her team partner with their patients through a unique and evidence based approach, blending the latest cutting-edge, medical care with comprehensive lifestyle changes, emphasizing nutrition, exercise, and stress management, to help her patients achieve optimal health.
Dr. Belardo is the co-chair of the American Society of Preventive Cardiology Nutrition Committee, a member of the American College of Cardiology Nutrition and Lifestyle Committee, and the Communications Catalyst for the California Chapter of American College of Cardiology.
Learn more about Dr. Belardo by clicking here.
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