Incretin Hormones: The role of GIP and GLP-1  

Written by Kelsey Schaffstall Young MS, RDN, LDN

On May 13 2022, the Food and Drug Administration approved a new medication called Mounjaro (tirzepatide) for the treatment of Type 2 diabetes.1 Results from clinical trials have shown that it is even more effective at regulating blood glucose and promoting weight loss than existing diabetes drugs.1 What sets Mounjaro apart is its unique formulation which combines the effects of two naturally occurring hormones that are responsible for blood glucose management, also known as incretin hormones.

What are Incretin hormones?

Incretin hormones are naturally occurring and they work to enhance insulin secretion and regulate blood glucose. They are produced and secreted in the gut and bind to receptors throughout the body; in the brain, on the pancreas, on adipose tissue, etc.1,3 Known as the “the incretin effect”, these hormones are responsible for the enhanced insulin secretion that is seen in response to glucose delivered to the gastrointestinal tract vs the same amount of glucose if it were administered directly into the bloodstream by an infusion.3

There are two Incretin hormones, GLP-1 and GIP. GLP-1 works by stimulating insulin secretion, promoting pancreatic beta cell growth, and decreasing glucagon release at meals.3 It also promotes satiety by slowing gastric emptying.3 GIP works to lower blood glucose by increasing insulin sensitivity, enhancing GLP-1 activity, and regulating appetite.3

How does diabetes affect Incretin hormones?

In Type 2 diabetes, there is little to no incretin-mediated insulin secretion due to the decreased secretion of GLP-1 and the decreased effect of GIP.3 Because of this, existing diabetes drugs work to enhance the effect of the Incretin hormones and reboot the Incretin Effect. GLP-1 analogs such as Semaglutide and Dulaglutide are popular medications that mimic the action of GLP-1. DPP-4 Inhibitors are also widely available and these medications work to inhibit an enzyme that breaks down GLP-1 and GIP, thereby extending their effects. 

A new class of drugs to treat diabetes

Mounjaro (tirzepatide), a once-weekly injectable, is the first of its kind in a new class of diabetes medications known as GLP-1 and GIP agonists. Meant to be used along with diet and exercise, it mimics both of the Incretin hormones producing a systemic glucose lowering effect similar to the naturally occurring Incretin effect.1

Clinical trials have shown that a 15mg dose of Mounjaro lowered HbA1c by 1.6% more than placebo when used alone and 1.5% more than placebo when combined with long-acting insulin.1,2 It lowered HbA1c by 0.5% more than Semaglutide, 0.9% more than Insulin Degludec and 1.0% more than Insulin Glargine.1,2 It also produced a weight loss effect, with 15 pounds more weight lost than placebo without insulin and 23 pounds more than placebo with insulin.1,2 

As research continues to evolve, there are more pharmaceutical options than ever for diabetes management that can help to prevent long term complications and promote longevity. If you are living with diabetes, consider working with a Registered Dietitian who can support you in making lifestyle changes to complement your treatment plan.

  1. A1C and weight change results: Mounjaro™ (tirzepatide). Mounjaro. (n.d.). Retrieved July 29, 2022, from 
  2. Commissioner, O. of the. (n.d.). FDA approves novel, dual-targeted treatment for type 2 diabetes. U.S. Food and Drug Administration. Retrieved July 29, 2022, from 
  3. Samms, R. J., Coghlan, M. P., & Sloop, K. W. (2020). How may GIP enhance the therapeutic efficacy of GLP-1? Trends in Endocrinology & Metabolism, 31(6), 410–421. 

Leave a Reply

%d bloggers like this: