GLP-1- The Good, the Bad, and the Ugly!

In recent years, there has been a great deal of interest in GLP-1 medications and its potential to provide therapeutic benefit. GLP-1 for years had been used exclusively for the treatment of type 2 diabetes but has now been found to have multiple beneficial effects on glucose metabolism and has been FDA approved to treat obesity. GLP-1 works by binding to GLP-1 receptors, which are located in a variety of tissues throughout the body including pancreas, brain and fat cells. However, is GLP-1 all that it is made out to be? In this blog post we will discuss what makes GLP-1 so special by delving into its features and effects on our bodies; taking into consideration both the good and bad side of things when discussing each aspect about GLP-1.

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WHAT IS GLP-1?

GLP-1 stands for Glucagon Like Peptide-1 and it is a hormone released from the intestines in response to food intake. GLP-1 is an incretin hormone and its primary role is to stimulate the release of insulin from the pancreas. GLP-1 also increases glucose uptake in the muscle cells, inhibits glucagon secretion from the pancreas and decreases appetite and food intake. GLP-1 acts on specific receptors present in multiple tissues throughout the body, including pancreatic beta cells, brain areas involved in reward processing, and fat cells.

GLP-1 AND DIABETES

GLP-1 is used in diabetes treatment to stimulate the release of insulin from the pancreas and decrease glucagon secretion. GLP-1 agonists (synthetic GLP-1 molecules) are used in combination with other therapies to improve glycemic control and reduce risk of hypoglycemia. GLP-1 agonists are approved for use as injectable medications and GLP-1 receptor antagonists are approved for use as oral medications. GLP-1 agonists have been shown to reduce HbA1c levels, improve glycemic control and reduce risk of hypoglycemia in individuals with type 2 diabetes.

GLP-1 AND OBESITY

In addition to its effects on glucose metabolism, GLP-1 has been found to have beneficial effects on obesity. GLP-1 agonists reduce food intake by decreasing the reward associated with eating. GLP-1 receptors are present in brain areas involved in reward processing, so GLP-1 agonists can decrease the motivation and drive to eat by disrupting these reward pathways. GLP-1 agonists also increase energy expenditure and reduce fat storage in the body. GLP-1 agonists are approved for use as injectable medications to help individuals with obesity achieve weight loss goals.

THE GOOD, THE BAD & THE UGLY OF GLP-1

The “good” of GLP-1 is that GLP-1 agonists have been found to reduce HbA1c levels, improve glycemic control and reduce risk of hypoglycemia in individuals with type 2 diabetes. GLP-1 agonists also have beneficial effects on obesity, reducing food intake and increasing energy expenditure. In a recent study, GLP-1 agonists were found to lead to an average of 7% weight loss in the treatment group versus 2.3 % in the placebo group, with GLP-1 therapy leading to greater reductions in body fat.

The “bad” of GLP-1 is that GLP-1 agonists can be expensive and may not be covered by insurance plans. GLP-1 agonists are injectable medications, so this can be inconvenient for some individuals. GLP-1 receptor antagonists may cause fluid retention and weight gain in some individuals.

The “ugly” of GLP-1 is that GLP-1 agonists can cause gastrointestinal side effects, including nausea and vomiting. GLP-1 receptor antagonists have also been linked to lean mass loss and increased risk of fractures. In a recent study, GLP-1 receptor antagonist therapy was associated with a significantly higher risk of fracture in women compared to GLP-1 agonist therapy. Additionally, in two semaglutide trials , DEXA scans revealed  a significant decrease in lean muscle mass associated with GLP-1 receptor antagonist therapy.

NOT ALL WEIGHT LOSS IS CREATED EQUAL

GLP-1 agonists have been found to be effective for weight loss, but it is important to understand that not all weight loss is created equal. Losing weight in itself  is not a cure for obesity. GLP-1 agonists are only one piece of the puzzle when it comes to weight loss and should be used in combination with lifestyle changes, such as increased physical activity and improved nutrition, to promote long-term success. GLP-1 agonists reduce food intake and increase energy expenditure, but they do not address underlying issues with emotional eating or lifestyle factors such as diet and lack of physical activity.

Body Composition vs Body Weight

When trying to reach weight loss goals, it is important to measure body composition (lean mass and fat mass) rather than just focusing on body weight. GLP-1 agonists have been linked to lean mass loss, so monitoring body composition can help ensure that individuals are losing fat and not muscle. Muscle is important because it helps burn calories and maintain a healthy metabolism, so preserving lean mass is important for long-term weight loss success. Fat loss while increasing muscle mass is the ultimate goal! Before starting these medications, it’s recommended to have a form of body compositional analysis to assess your baseline, such as a DEXA scan.

BODY COMPOSITION AND LONGEVITY

Recently on the blog, we discussed how strength training is a critical piece of the puzzle for optimal longevity.  GLP-1 agonists can be helpful for weight loss, but it is important to understand that GLP-1 agonists cannot replace strength training for optimal longevity. Our body composition and muscle strength are important for maintaining our quality of life and independence as we age, so it is important to focus on building muscle mass and not just the number on the scale.

TOO MUCH OF A GOOD THING

While GLP-1 can be an excellent way to improve glycemic control and reduce risk of hypoglycemia, GLP-1 agonists should not be taken indefinitely. GLP-1 agonists can have serious side effects in some individuals and long-term use of GLP-1 agonists is associated with an increased risk of fractures. Thus, GLP-1 agonists should be used responsibly under the supervision of a healthcare provider after weighing out risks and benefits.