GLP-1 Receptor Agonist Medication: An Overview

GLP-1 AGONISTS: AN OVERVIEW

In the past two decades, there have been several game-changing advancements in obesity treatment—the most notable being the development of a new class of medications called GLP-1 (glucagon-like peptide-1) receptor agonists. At Calibrate, we use GLP-1s in combination with our proprietary intensive lifestyle intervention (ILI) to impact physiology most important for sustained weight loss and improved metabolic health.

What Are GLP-1 Agonists Prescribed For?

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of prescription medications that have been proven to be effective in the treatment of type 2 diabetes and obesity. These Food and Drug Administration (FDA) approved medications help manage blood glucose levels to treat type 2 diabetes and suppress hunger and appetite while optimizing biology for weight loss.  Promising studies also show the beneficial effects of these medications on cardiovascular disease. 

How Safe Are GLP-1 Agonists?

GLP-1s are FDA-approved, clinically-tested, stimulant-free, and non-habit forming. Not only are they safe, but research shows that they're the most effective medications for sustainable weight loss, especially when combined with lifestyle changes.

GLP-1s are generally very well tolerated, with limited side effects. Many individuals don’t have any side effects at all, but for those who do, nausea is the most common, and this typically resolves over the first few weeks of use. In most recent clinical trials, at the highest dose, less than 5% of people discontinued GLP-1 medications because of side effects. 

Our members have direct access to their Calibrate Medical Team through secure messaging for help with titrating onto prescribed medications and managing any side effects experienced. The member’s Medical Team is also available throughout the program for any questions about medication side effects or other medical concerns.

How Do GLP-1 Agonists Work? 

GLP-1 medications work by stimulating the secretion of insulin and slowing the release of glucagon into the body, influencing blood sugar control. They also help with weight loss by acting on the body’s set point (the weight the body fights to maintain), reducing appetite and increasing satiety.

The effectiveness of GLP-1 medications are best understood through observing the body's naturally occurring GLP-1 hormone. GLP-1 is an incretin hormone that is produced in the gut. Activated by food intake, the GLP-1 hormone stimulates insulin secretion to normalize blood sugars as well as communicate feelings of satiety (feeling full) through action on the hypothalamus and hindbrain. This hormone also causes delayed gastric emptying which can increase and extend feelings of fullness after eating. Research suggests that people who hold onto more weight or chronically diet experience reductions in GLP-1 signaling which can cause persistent feelings of hunger.

Here’s a closer look at the many ways in which the GLP-1 hormone interacts with other organ systems:

• Brain: GLP-1 receptors in the hypothalamus—the part of the brain responsible for appetite and thirst—tell us to stop eating and make food less appealing
• Muscles: GLP-1 increases fatty acid and glucose uptake so it can then be broken down (via beta oxidation or glycolysis) as a fuel source
• Stomach: GLP-1 slows down the rate at which food is digested and is cleared from the stomach, helping prolong the sensation of fullness after a meal and with smaller portions
• Liver:  GLP-1 suppresses hepatic glucose production (gluconeogenesis), which helps lower sugar levels in people with impaired blood sugar metabolism
• Pancreas:  GLP-1 triggers insulin secretion and suppresses glucagon secretion, resulting in improved blood sugar control and utilization of sugar for energy and storage in the body; this is particularly important in people who have impaired glucose tolerance, pre-diabetes, or diabetes

How Effective Are GLP-1 Agonists?

The use of GLP-1 medications can not only lead to weight loss that was previously only achievable with surgery, but can help to reduce the risk of other chronic diseases related to metabolic health such as diabetes, high blood pressure, cholesterol, and fatty liver disease. At one year, Calibrate members lose an average of 15% of their body weight, significantly higher than the 7-8% seen in clinical trial research for the GLP-1 medications taken by more than 95% of our members. These results are only possible by combining the use of clinically appropriate medications with our holistic, proprietary intensive lifestyle intervention that emphasizes lifestyle change.

What GLP-1 Agonists Are Prescribed by Calibrate Doctors?

Calibrate doctors prescribe a select number of GLP-1 agonists that are either indicated specifically for weight loss or indicated for off-label use for weight loss. These medications include the following, listed in alphabetical order by brand name: 

Mounjaro® (tirzepatide)

• Drug class: GLP-1 Agonists
• What is Mounjaro®? Mounjaro™ is a once-weekly injectable medication that helps regulate blood sugar levels. Currently, it is indicated for use in patients with type 2 diabetes, but it shows promise as a weight-loss drug as well.
• Dose: The starting dosage of Mounjaro® is 2.5 mg. After 4 weeks, doses may be increased in 2.5 mg increments, as tolerated, up to a maximum of 15 mg once weekly.
• Manufacturer: Eli Lilly and Company

Ozempic® (semaglutide)

• Drug class: GLP-1 Agonists
• What is Ozempic®? Ozempic® is a once-weekly subcutaneous injectable medication and one of the GLP-1 medications prescribed by Calibrate doctors. It has been FDA-approved since 2017. While Ozempic® is currently FDA-approved for use in patients with type-2 diabetes, there is proof that its active ingredient is safe and effective in treating overweight or obesity. Just as it does in adults with type-2 diabetes, Ozempic® can improve blood sugar levels in adults with insulin resistance or prediabetes, and is an effective tool for weight loss among both groups. 
• Dose: The starting dose of Ozempic® is 0.25 mg once a week and titrates up to 2.0 mg once a week. This medication comes in a pre-filled pen.  
• Manufacturer: Novo Nordisk

Rybelsus® (oral semaglutide)

• Drug class: GLP-1 Agonists 
• What is Rybelsus®? Rybelsus® is a once-daily oral prescription medicine and one of the GLP-1 medications prescribed by Calibrate doctors. Unlike many other GLP-1 medications, Rybelsus is taken orally (in tablet form) each morning on an empty stomach. While Rybelsus® is currently FDA-approved for use in patients with type-2 diabetes, there is proof that its active ingredient is safe and effective in treating overweight or obesity. Just as it does in adults with type-2 diabetes, Rybelsus® can improve blood sugar levels in adults with insulin resistance or prediabetes, and is an effective tool for weight loss among both groups. 
• Dose: The beginning dose of Rybelsus® is 3 mg once daily and titrates up to 14 mg once daily. 
• Manufacturer: Novo Nordisk

Saxenda® (liraglutide)

• Drug class: GLP-1 Agonists
• What is Saxenda®? Saxenda® is a safe, FDA-approved GLP-1 medication prescribed for weight loss. It is a once-daily subcutaneous injectable prescription medicine indicated for adults with excess weight who also have weight-related medical problems or obesity, and children aged 12-17 years with a bodyweight above 132 pounds (60 kg) and obesity to help them lose weight and keep the weight off. Saxenda® should be used in conjunction with intensive lifestyle interventions including healthy food choices and exercise. Saxenda® is one of the GLP-1 medications prescribed by Calibrate doctors.  
• Dose: The beginning dose of Saxenda® is 0.6 mg and titrates up to 3.0 mg. This medication comes in a prefilled pen. 
• Manufacturer: Novo Nordisk

Trulicity® (dulaglutide)

• Drug class: GLP-1 Agonists
• What is Trulicity®? Trulicity® is a once-weekly subcutaneous injectable medicine and one of the GLP-1 medications prescribed by Calibrate doctors. While Trulicity® is currently FDA-approved for use in patients with type-2 diabetes for glycemic control, there is proof that its active ingredient is safe and effective in treating overweight or obesity. Just as it does in adults with type-2 diabetes, Trulicity® can improve blood sugar levels in adults with insulin resistance or prediabetes, and is an effective tool for weight loss among both groups. 
• Dose: Patients start with 0.75 mg subcutaneous injections weekly; doses titrate up to a maximum of 4.5 mg weekly. This medication comes in a prefilled autoinjector. 
• Manufacturer: Eli Lilly and Company

Wegovy® (semaglutide)

• Drug class: GLP-1 Agonists
• What is Wegovy®? Wegovy® is a once-weekly subcutaneous injectable GLP-1 that was approved by the FDA for weight loss in June 2021. It is one of the medications prescribed by Calibrate doctors to work in conjunction with the Calibrate One Year Metabolic Reset. It is one of only six medications currently approved by the FDA for the treatment of obesity.
• Dose: The beginning dose of Wegovy® is 0.25 mg subcutaneous once weekly and titrates up to a maintenance dose of 2.4 mg once weekly. This medication comes in a prefilled pen. 
• Manufacturer: Novo Nordisk