Mounjaro banner

GIP Is 1 of 2 Incretin Hormones—Along With GLP-1—That Has Diverse Metabolic Roles1

GIP and GLP-1 drive the incretin effect, which leads to insulin release and postprandial glucose clearance1

These hormones are secreted by the gut in response to nutrient load. They are responsible for the incretin effect, which enhances the secretion of insulin after a meal.2

GIP is responsible for nearly two-thirds of the incretin effect in healthy humans, contributing more to insulin secretion than GLP-1.1

The incretin effect is diminished in patients with T2D1

blood glucose icon

A diminished incretin effect is associated with hyperglycemia. Over time, hyperglycemia is associated with nephropathy, retinopathy, neuropathy, and cardiovascular disease.1,3

Recent studies suggest several additional functions for GIP and GLP-14-7

GLP-1 is known to regulate body weight via its actions in the CNS. Similarly, GIP receptors are found in areas of the CNS that may regulate body weight through appetite and food intake mechanisms.8-10

Preclinical studies have also shown GIP receptors in areas of the brain known to act on appetite control centers, which may reduce caloric consumption.8,11,12

While GLP-1 RAs can improve insulin sensitivity in patients with T2D, it may be the result of weight loss. But GIP has displayed direct effects on insulin sensitivity in preclinical studies.4-5

Comparison of Proposed Actions of GIP And GLP-15

Mounjaro is the first and only approved single-molecule GIP and GLP-1 receptor agonist

Discover the efficacy of Mounjaro

LEARN MORE

CNS=central nervous system; GIP=glucose-dependent insulinotropic polypeptide; GLP-1=glucagon-like peptide-1; RA=receptor agonist; GLP-1 RA=glucagon-like peptide-1 receptor agonist; T2D=type 2 diabetes.

References:

  1. Nauck MA, Meier JJ. GIP and GLP-1: stepsiblings rather than monozygotic twins within the incretin family. Diabetes. 2019;68(5):897-900.
  2. Nauck MA, Meier JJ. The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions. Lancet Diabetes Endocrinol. 2016;4(6):525-536.
  3. American Diabetes Association. Standards of medical care in diabetes—2022. Diabetes Care. 2022;45(suppl1):S1-S264.
  4. Mohammad S, Ramos LS, Buck J, et al. Gastric inhibitory peptide controls adipose insulin sensitivity via activation of cAMP-response element-binding protein and p110β isoform of phosphatidylinositol 3-kinase. J Biol Chem. 2011;286(50):43062-43070.
  5. Samms RJ, Coghlan MP, Sloop KW. How may GIP enhance the therapeutic efficacy of GLP-1? Trends Endocrinol Metab. 2020;31(6):410-421.
  6. Finan B, Müller TD, Clemmensen C, et al. Reappraisal of GIP pharmacology for metabolic diseases. Trends Mol Med. 2016;22(5):359-376.
  7. 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;23(suppl 3):5-29.
  8. Adriaenssens AE, Biggs EK, Darwish T, et al. Glucose-dependent insulinotropic polypeptide receptor-expressing cells in the hypothalamus regulate food intake. Cell Metab. 2019;30(5):987-996.e6.
  9. Samms RJ, Coghlan MP, Sloop KW. How may GIP enhance the therapeutic efficacy of GLP-1? Trends Endocrinol Metab. 2020;31(6):410-421.
  10. van Bloemendaal L, ten Kulve JS, la Fleur SE, et al. Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS. J Endocrinol. 2014;221(1):T1-T16.
  11. Adriaenssens AE, Gribble FM, Reimann F. The glucose-dependent insulinotropic polypeptide signaling axis in the central nervous system. Peptides. 2020;125(3):170194
  12. Samms RJ, Sloop KW, Gribble FM, et al. GIPR function in the central nervous System: implications and novel perspectives for GIP-based therapies in treating metabolic disorders. Diabetes. 2021;70(9):1938-1944.

Indication

Mounjaro (tirzepatide), an injectable prescription medicine, is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Limitations of Use: Mounjaro has not been studied in patients with a history of pancreatitis. Mounjaro is not indicated for use in patients with type 1 diabetes mellitus.

Important Safety Information

WARNING: RISK OF THYROID C-CELL TUMORS

In both male and female rats, tirzepatide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Mounjaro causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined.

Mounjaro is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Mounjaro and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Mounjaro.

Mounjaro is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, and in patients with known serious hypersensitivity to tirzepatide or any of the excipients in Mounjaro.

Risk of Thyroid C-cell Tumors

Counsel patients regarding the potential risk for MTC with the use of Mounjaro and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Mounjaro. Such monitoring may increase the risk of unnecessary procedures, due to the low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin values may indicate MTC and patients with MTC usually have calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.

Pancreatitis

Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists. Pancreatitis has been reported in Mounjaro clinical trials. Mounjaro has not been studied in patients with a prior history of pancreatitis. It is unknown if patients with a history of pancreatitis are at higher risk for development of pancreatitis on Mounjaro. Observe patients for signs and symptoms, including persistent severe abdominal pain sometimes radiating to the back, which may or may not be accompanied by vomiting. If pancreatitis is suspected, discontinue Mounjaro and initiate appropriate management.

Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin

Concomitant use with an insulin secretagogue (e.g., sulfonylurea) or insulin may increase the risk of hypoglycemia, including severe hypoglycemia. The risk of hypoglycemia may be lowered by reducing the dose of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.

Hypersensitivity Reactions

Hypersensitivity reactions, sometimes severe, have been reported with Mounjaro in clinical trials. If hypersensitivity reactions occur, discontinue use of Mounjaro; treat promptly per standard of care, and monitor until signs and symptoms resolve. Do not use in patients with a previous serious hypersensitivity to Mounjaro. Use caution in patients with a history of angioedema or anaphylaxis with a GLP-1 receptor agonist because it is unknown if such patients will be predisposed to these reactions with Mounjaro.

Acute Kidney Injury

Mounjaro has been associated with gastrointestinal adverse reactions, which include nausea, vomiting, and diarrhea. These events may lead to dehydration, which if severe could cause acute kidney injury. In patients treated with GLP-1 receptor agonists, there have been postmarketing reports of acute kidney injury and worsening of chronic renal failure, sometimes requiring hemodialysis. Some of these events have been reported in patients without known underlying renal disease. A majority of reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. Monitor renal function when initiating or escalating doses of Mounjaro in patients with renal impairment reporting severe adverse gastrointestinal reactions.

Severe Gastrointestinal Disease

Use of Mounjaro has been associated with gastrointestinal adverse reactions, sometimes severe. Mounjaro has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients.

Diabetic Retinopathy Complications in Patients with a History of Diabetic Retinopathy

Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Mounjaro has not been studied in patients with non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy.

Acute Gallbladder Disease

In clinical trials, acute gallbladder disease was reported by 0.6% of Mounjaro-treated patients and 0% of placebo-treated patients. If cholelithiasis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated.

The most common adverse reactions reported in ≥5% of Mounjaro-treated patients in placebo-controlled trials were nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, and abdominal pain.

Drug Interactions

When initiating Mounjaro, consider reducing the dose of concomitantly administered insulin secretagogues (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia. Mounjaro delays gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications, so caution should be exercised.

Pregnancy

Limited data on Mounjaro use in pregnant women are available to inform on drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Based on animal reproduction studies, there may be risks to the fetus from exposure to tirzepatide. Use only if potential benefit justifies the potential risk to the fetus.

Lactation

There are no data on the presence of tirzepatide in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Mounjaro and any potential adverse effects on the breastfed infant from Mounjaro or from the underlying maternal condition.

Females of Reproductive Potential

Advise females using oral hormonal contraceptives to switch to a non-oral contraceptive method, or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation.

Pediatric Use

Safety and effectiveness of Mounjaro have not been established and use is not recommended in patients less than 18 years of age.

Please click to access Prescribing Information, including Boxed Warning about possible thyroid tumors, including thyroid cancer, and Medication Guide.
Please see Instructions for Use included with the pen.

TR HCP ISI MAY2022