Dual acting GLP-1 and GIP Receptor Agonist - Tirzepatide

A synthetic dual-acting GIP and GLP-1 receptor agonist (Tirzepatide) is available for the treatment of hyperglycemia in patients with type 2 diabetes]. The effect of Tirzepatide is largely mediated by its GIP component. Tirzepatide has a half-life of five days, allowing for once-weekly administration.

Tirzepatide: All of the information above re: GLP-1 receptor agonists apply to Tirzepatide as well as Semaglutide, as the risks, benefits, and side effects are synonymous; but here are some specifics from Mounjaro’s website.

❖ In both male/female rats causes dose-dependent thyroid C-cell tumors
❖ Unknown whether Mounjaro causes thyroid C-cell tumors including medullary thyroid carcinoma (MTC) in humans
❖ Mounjaro is contraindicated in pt’s w/ personal or family hx of MTC or in pt’s w/ MEN 2 (multiple endocrine neoplasia type 2)
❖ Risk of Pancreatitis
➢ Do baseline labs for Lipase/Amylase
➢ Repeat labs every 3 months
➢ If symptoms of Pancreatitis DC Rx refer to PCP
➢ If slightly elevated and asymptomatic evaluate and use clinical judgment
➢ Exacerbated with alcohol use; discourage pt’s from excessive drinking
❖ Risk of hypoglycemia w/ concomitant use of insulin secretagogues or insulin
❖ Hypersensitivity rxn’s sometimes severe have been reported
❖ Acute kidney injury related to gastrointestinal conditions secondary to dehydration have been reported
❖ Associated w/ gastrointestinal adverse rxn’s, sometimes severe
❖ Diabetic retinopathy complications in patients w/ Hx of diabetic retinopathy
➢ The rapid improvement in glucose control has been associated with the temporary worsening of diabetic retinopathy
❖ Acute gallbladder disease was reported by 0.6% of users in a study
❖ Drug interactions- the potential impact on medications as they delay gastric emptying
❖ Pregnancy- Limited data. Based on animal studies there may be risks to the fetus; use only if the potential benefit justifies the potential risk to the fetus

Clinical Pearls- Tirzepatide:
❖ Same as above for the GLP-1 section
❖ We have seen Tirzepatide work better than Semaglutide for weight loss in some patients, as it should on paper; but there are some people who respond better to Semaglutide as well.
➢ Generally we can tell by the first few doses (2.5mg, 3.5mg, and 5mg)
➢ For our patients that are looking to lose > 30lbs we encourage Tirzepatide (though we have had pt’s lose > 30lbs w/ Semaglutide as well)
➢ For those who only need to lose 10-15 lbs, we have found Tirzepatide to be too aggressive at times (they lose too much too fast, and don’t feel so great)
➢ For the patients who need between 20-30 lbs weight loss, our decision is subjective based on all of our information (H&P, BCA, Labs, medications, lifestyle, financial consideration)
➢ We have had very few pt’s need to go up to 7.5mg, 10mg, or above; we think this is because of 1) the efficacy of the medication working on 2 receptors, compared to just one (Semaglutide), 2) our combination proprietary protocols, and 3) our advisement and monitoring
➢ Patient’s who struggle to get the most optimal results
■ Check on their alcohol habits; daily drinkers (2-3 glasses wine/evening) have struggled
■ Sedentary patients unwilling to exercise
■ Patients w/ gut inflammation (constipation, bloating, distended, poor diets)
For the best results they need to have a healthy gut; address the microbiome
◆ Enforce that they use a prebiotic (more important than a probiotic) every day; not just stop after 2 weeks
◆ If you suspect prior to start, also recommend Prolon for 5 days (fasting-mimicking diet- great to do while they are waiting for their medication to arrive; as we don’t think it is safe for them to do together-> hypoglycemia concerns
◆ Hx of GERD: Alka Seltzer Gold- AM/ PM (amazing longevity hack)
◆ Hx Barrett’s Esophagus: Alka Seltzer Gold and Oral BPC 157 (very successful protection; heals ulcers, prevents new damage)

Tirzepatide Dosage:
❖ Advitam dosing:
➢ Our pharmacy compounds Tirzepatide w/ BPC 157 & Vit B6
➢ One of our other pharmacies compounds Tirzepatide w/ Vit B12
➢ The vials come in different strengths and volumes
➢ Depending on the H&P, labs, body composition analysis, medications, and goals of the patient, there are different options
■ For the typical patient, titrate:
● Inject 2.5mg SubQ q 7d x 4 wks
● Inject 3.5mg SubQ q 7d x 4 wks (at 7 week f/u determine if needs to increase or hold here)
● Inject 5.0mg SubQ q 7d (until further consultation- either by phone or office visit)
➢ Depending on the Strength compounded in the vial (which varies from pharmacy to pharmacy and sometimes within different strengths from the same pharmacy) will determine the volume to be administered in units. For example:
➢ Pharmacy A: 10 units equals 0.25mg
➢ Pharmacy B: 12 units equals 0.25mg
➢ Don’t worry we have worked hard in trying to make it easy for you and we will teach you how to make adjustments if necessary.