Bring GLP-1 Activity into the conversation to help your T2D patients better understand their disease

GLP-1 Activity is an element of type 2 diabetes and should be included when talking with your patients in order to help them understand what is happening in their body when it responds to high blood sugar.1-3

GLP-1=glucagon-like peptide-1

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Experts Richard Pratley, MD, and Ralph DeFronzo, MD, explain more about native GLP‑1 and other factors that contribute to type 2 diabetes.


Richard Pratley, MD


Ralph DeFronzo, MD

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GLP-1 Activity in a healthy person:

Sufficient signals to lower blood glucose levels1-3

GLP-1 is released from the gut in response to food intake.3

Experimental models of diabetes have shown that the GLP-1 Activity signal, among other signals,* helps to lower blood glucose and regulate metabolic responses by facilitating the communications among organs.1-3

*Additional signals include increased plasma concentrations of amino acids such as arginine, leucine, and lysine, as well as parasympathetic stimulation via the vagus nerve.3

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GLP-1 Activity in type 2 diabetes:

Insufficient signals to lower blood glucose levels12-14

The response to food is no longer appropriate because the GLP-1 Activity signal strength is inadequate. This contributes to, among other things, inadequate insulin secretion from the pancreas.12-15

Subpar GLP-1 Activity may be directly or indirectly linked to metabolic defects in type 2 diabetes.4

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GLP-1 RAs help boost GLP-1 Activity1,4,16

GLP-1 RAs mimic native GLP-1, inducing GLP-1 Activity in the pancreas, liver, and stomach1,4,16

Like native GLP-1, GLP-1 RAs directly stimulate GLP-1 receptors. Boosted GLP-1 Activity helps ensure the communications are received and acted upon.1,4,17

GLP-1 RAs=glucagon-like peptide-1 receptor agonists.

The role of GLP-1 Activity and GLP-1 RAs

In patients with type 2 diabetes,

GLP-1 Activity is insufficient to signal the lowering of blood glucose levels12-14


GLP-1 RAs mimic native GLP-1, inducing GLP-1 Activity in the pancreas, liver, and stomach1,4,17

Learn more about how GLP-1 works in the body

Understanding the role of GLP-1 in type 2 diabetes


Richard Pratley, MD

Diabetes Program Lead
AdventHealth Translational Research Institute for Metabolism and Diabetes
Orlando, Florida

The progressive nature of type 2 diabetes: beta-cell dysfunction and apoptosis


Ralph DeFronzo, MD

Professor of Medicine
Chief, Diabetes Division
University of Texas Health Science Center
Texas Diabetes Institute
San Antonio, Texas

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References:

  1. Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740-756.
  2. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131-2157.
  3. Aronoff SL, Berkowitz K, Shreiner B, Want L. Glucose Metabolism and Regulation: Beyond Insulin and Glucagon. Diabetes Spectrum. 2004;17(3):183-190.
  4. Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanism of incretin hormone action. Cell Metab. 2013;17(6):819-837.
  5. Muscogiuri G, DeFronzo RA, Gastaldelli A, Holst JJ. Glucagon-like peptide-1 and the central/peripheral nervous system: crosstalk in diabetes. Trends Endocrinol Metab. 2017;28(2):88-103.
  6. Nauck MA, Quast DR, Wefers J, Pfeiffer AFH. The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: a pathophysiological update. Diabetes Obes Metab. 2021. [in press].
  7. Kimura T, Obata A, Shimoda M, et al. Down-regulation of vascular GLP-1  receptor expression in human subjects with obesity. Sci Rep. 2018;8(1):10644.
  8. Müller TD, Finan B, Bloom SR, et al. Glucagon-like peptide-1 (GLP-1). Mol Metab. 2019;30:72-130.
  9. Li J, Zheng J, Wang S, Lau HK, Fathi A, Wang Q. Cardiovascular benefits of native GLP-1 and its metabolites: an indicator for GLP-1-therapy strategies. Front Physiol. 2017;8:15.
  10. Druce MR, Small CJ, Bloom SR. Minireview: gut peptides regulating satiety. Endocrinology. 2004;145(6):2660-2665.
  11. Kanoski SE, Hayes MR, Skibicka KP. GLP-1 and weight loss: unraveling the diverse neural circuitry. Am J Physiol Regul Integr Comp Physiol. 2016;310(10):R885-R895.
  12. Herzberg-Schäfer S, Heni M, Stefan N, Häring H-U, Fritsche A. Impairment of GLP1-induced insulin secretion: role of genetic background, insulin resistance and hyperglycaemia. Diabetes Obes Metab. 2012;14(suppl 3):85-90.
  13. Kjems LL, Holst JJ, Vølund A, Madsbad S. The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes. 2003;52(2):380-386.
  14. Calanna S, Christensen M, Holst JJ, et al. Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: systematic review and meta-analyses of clinical studies. Diabetologia. 2013;56(5):965-972.
  15. Højberg PV, Vilsbøll T, Rabøl R, et al. Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia. 2009;52(2):199-207.
  16. Hinnen D. Glucagon-like peptide 1 receptor agonist for type 2 diabetes. Diabetes Spectrum. 2017;30(3):202-210.
  17. Wick A, Newlin K. Incretin-based therapies: therapeutic rationale and pharmacological promise for type 2 diabetes. J Am Acad Nurse Pract. 2009;21(suppl 1):623-630.

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