According to the World Health Organization (WHO), overweight and obesity are defined as “abnormal or excessive fat accumulation that presents a health risk. A body mass index (BMI) over 25 is considered overweight, and over 30 is obese.”1 The United States Centers for Disease Control and Prevention cites poor diet and low physical activity levels as risk factors for obesity, affecting approximately 42% of adults and 20% of children.2
The prevalence of obesity is climbing in segments of the population and areas of the world in which it has not previously been a concern, including a fourfold increase in obesity rates in children since the mid-1970’s.1 The current approach to weight loss by medical providers focuses initially on treating underlying causes and then on optimizing lifestyle factors such as diet and exercise.
Surgical options for treating obesity have been around for decades (eg. Gastric bypass, gastric sleeve). In recent years, the pharmaceutical industry has introduced a number of medications that have been proven effective at reducing weight compared to placebo. There are two glucagon-like peptide-1 (GLP-1) receptor agonists that have been approved for the treatment of obesity in the United States: semaglutide and liraglutide. Both of these medications are injectable. The brand names for semaglutide include: Ozempic, Rybelsus, and Wegovy. The brand names for liraglutide include: Saxenda and Victoza.
These medications work by allowing your body to use insulin more effectively, slowing down your digestion, and by acting on areas of the brain involved in managing your appetite.3 Insulin is a hormone that allows your cells to use the glucose from your food. One diagnosis commonly associated with obesity is type 2 Diabetes. In type 2 Diabetes, your body becomes less able to make insulin and less responsive to the insulin it does make. This makes it difficult for all your body’s cells to function properly. The GLP-1 agonists can be used as a treatment option for type 2 Diabetes in certain patients.
The most common side effects from GLP-1 agonists include abdominal pain, constipation, nausea, vomiting, and diarrhea. The slowed digestion caused by these medications is also known as delayed gastric emptying. Delayed gastric emptying leads to people feeling fuller after each meal for longer.3 Nausea can result if you attempt to eat while feeling full. GLP-1agonists should not be used in people with a history of pancreatitis, people with type 1 diabetes, and those who are pregnant or planning to become pregnant.
GLP-1 agonists are not meant to be prescribed for everyone. People who qualify for this medication as a weight management treatment must have a BMI of greater than or equal to 30. Alternatively, patients who have a BMI greater than or equal to 27 AND another medical condition due to being overweight (eg. High blood pressure, high cholesterol) will qualify.
A combination of lifestyle modifications and anti-obesity medications has shown efficacy in clinical trials.4,5 The response to GLP-1 agonists varies widely between patients. People need to work closely with a healthcare provider to find the optimal dose of the medication that is right for them. Not only will you need to have your weight closely monitored, but many providers will likely also monitor your blood pressure and heart rate regularly. If you do not lose 4-5% of your body weight after 3 months of medication at the highest tolerated dose, your healthcare provider will likely assist you in slowly stopping the medication. There are not currently clear guidelines for trying alternative GLP-1 agonists or other medication therapies if the initial medication did not work. The decision to trial other therapies will be up to each individual patient and provider.
At a certain point, people will stop losing weight while on these medications and may need additional strategies for more weight loss. Weight gain can be expected when these medications are stopped. This weight gain occurs because our bodies work very hard to maintain their preferred weight. Our baseline ability to burn calories will decrease with weight loss6 and the hormones that tell us we are hungry will go into overdrive to return to our internal set point.7 Scientists continue to study the long-term effects of weight loss on our metabolism and hormones because most people regain lost weight within 2-3 years.8 Therefore, if weight loss is successfully achieved with a GLP-1 agonist, continuing them longer term may be necessary to maintain the benefits.
Are these medications right for you? You will need to consult your healthcare provider to determine if you qualify for these medications and if they are right for you.
1. Obesity (who.int)
2. HOP 2023 | NOFO | DNPAO | CDC
3. Glucagon-Like Peptide-1 Receptor Agonists – StatPearls – NCBI Bookshelf (nih.gov)
4. Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, Loomba R, Camilleri M, Singh S. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016 Jun 14;315(22):2424-34. doi: 10.1001/jama.2016.7602. Erratum in: JAMA. 2016 Sep 6;316(9):995. PMID: 27299618; PMCID: PMC5617638.
5. Rubino DM, Greenway FL, Khalid U, O’Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150. doi: 10.1001/jama.2021.23619. PMID: 35015037; PMCID: PMC8753508.
6. Rosenbaum M, Hirsch J, Gallagher DA, Leibel RL. Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. Am J Clin Nutr. 2008 Oct;88(4):906-12. doi: 10.1093/ajcn/88.4.906. PMID: 18842775.
7. Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, Proietto J. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011 Oct 27;365(17):1597-604. doi: 10.1056/NEJMoa1105816. PMID: 22029981.
8. Maintaining Weight Loss | Johns Hopkins Medicine