Episode 96: Tirzepatide.
By Maria Beuca, MS3, Ross University School of Medicine. Comments by Hector Arreaza, MD.
Today is May 19, 2022, and we want to talk about a new drug that was recently approved by the FDA on May 13, 2022, for the treatment of type 2 diabetes.
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This drug is known as tirzepatide, also known by the brand name Mounjaro®. It is an injection given once a week that mimics the effects of two hormones: GIP (Glucose-dependent Insulinotropic Polypeptide) and GLP-1 (Glucagon-Like Peptide-1). These two hormones are involved in lowering blood glucose levels after eating by stimulating insulin release, they are “incretin” hormones.
What is unique about this new drug, tirzepatide, is that it is the first and only approved single molecule that binds and activates BOTH GIP and GLP-1 receptors. Because of this dual incretin action, it has also been referred to as a “twincretin.” It increases first and second-phase insulin secretion AND decreases glucagon levels in a glucose-dependent manner, and this lowers both fasting blood glucose levels and post-meal glucose levels.
It is also an appetite suppressant, causing significant weight loss in patients with type 2 diabetes.
Tirzepatide vs semaglutide: Semaglutide (Ozempic®) was approved for the treatment of type 2 Diabetes in December 2017, and then approved for weight loss in June 2021 under the brand name Wegovy®.
Semaglutide is a GLP-1 receptor agonist, but it does not work on GIP receptors. Due to this dual incretin action of tirzepatide, it has now been shown to be superior at all doses to semaglutide.
Evidence: There was a 40-week study done in July 30, 2019- February 15, 2021, called “SURPASS-2” where 1879 patients were assigned in a 1:1:1:1 ratio to either semaglutide 1 mg or to the 3 different doses of tirzepatide (5 mg, 10 mg, 15 mg). The patients all had a mean HbA1c of 8.28% at the start of the study.
By the end of the study, the patients on tirzepatide at the different doses had an A1c of 6.2% for the 5mg dose, 6 % for the 10 mg dose, and 5.9% for the 15 mg dose, whereas the patients on semaglutide had their HbA1c at 6.42%.
On tirzepatide, about 82-86% of patients decreased their HbA1c below 7.0%, compared to 79% of the patients on semaglutide.
Comment: It seems like a race: All GLP-1 RA are competing to reach the lowest A1C and get the lowest weight. What is more amazing is that up until now, an A1c level < 5.7% without a risk of hypoglycemia was not considered attainable with current treatment options, but with tirzepatide, this goal was met.
Fasting Serum glucose levels prior to treatment: 173. Fasting Serum glucose after treatment with:
Tirzepatide 5 mg: 117.0, 10 mg: 111.3, 15 mg: 109.6. Semaglutide 1 mg: 124.4.
Comment: No hypoglycemia.
Weight loss for patients on Tirzepatide was also greater, patients lost about 4 to 12 lbs more (1.9 to 5.5 kg) than with semaglutide. Weight loss in 40 weeks: Tirzepatide: 5mg: 16 lbs (7.6 kg), 10 mg: 20 lbs (9.3 kg), 15 mg: 24 lbs (11.2 kg). Semaglutide: 12 lbs (5.7 kg).
Other positive effects that many patients experience were: improved lipid profile, blood pressure, liver enzymes, and improved biomarkers of insulin sensitivity.
Another Phase 3 clinical trial of tirzepatide that is currently ongoing is the SURMOUNT-1, which focuses on the weight loss benefits of the drug, and results are expected in 2023. Preliminary data shows that tirzepatide has similar weight loss as bariatric surgery.
Cost: Tirzepatide (Mounjaro) is a rival for Novo Nordisk’s semaglutide sold as Ozempic and Wegovy.
Institute for Clinical and Economic Review (ICER) released the final report for tirzepatide cost: $5,500-5,700/year. Semaglutide: Ozempic, Wegovy ~ $16,000/year without insurance.
Comment: [3 times cheaper]. 4x more expensive in the US, rarely covered by health insurance for weight loss
Administration: 1x week, any time, with or without meals. Doses: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg. Week 1-Week 4: Start with 2.5 mg injection 1x week. Treatment initiation, not intended for glycemic control. Week 5-Week 8: Increase to 5.0 mg 1x week. >Week 9: may increase dose another 2.5 mg every 4 weeks as needed for glycemic control. Maximum dose: 15 mg 1x week.
Adverse Reactions: Nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, abdominal pain.
Drug Interactions: Delays gastric emptying, can affect absorption of oral medications taken at the same time. Warfarin = monitor more closely.
Contraindications: Type 1 diabetes, pregnancy, personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2: medullary thyroid cancer, parathyroid tumors, and pheochromocytoma). Thyroid c-cell tumors were noticed in rats. Symptoms of thyroid cancer: mass in neck, dysphagia, dyspnea, persistent hoarseness.
Warnings & Precautions:
Pancreatitis: Has been reported in clinical trials. Discontinue if suspected.
Hypoglycemia: May cause hypoglycemia if used with insulin or insulin secretagogues (sulfonylurea). Reducing dose of these may be necessary.
Hypersensitivity is possible.
Acute Kidney Injury: No dosage adjustment needed, but monitor renal function if patient has renal impairment with severe GI reactions. It may cause nausea, vomiting and diarrheaà dehydrationà acute kidney injury. Can worsen chronic renal disease or renal impairment.
Severe gastrointestinal disease: May cause Gastrointestinal adverse reactions, sometimes severe. Not recommended in patients with severe gastrointestinal disease, may aggravate symptoms, has not been studied.
Acute gallbladder disease: Also has occurred in 0.6% of patients in trials. monitor and follow-up if cholelithiasis is suspected.
Diabetic retinopathy: Not studied, monitor for complications. Rapid glucose control can cause temporary worsening of diabetic retinopathy, monitor these patients.
Pregnancy: May cause fetal harm.
Females of Reproductive potential: If using oral contraceptives, switch to non-oral contraceptive or add a barrier method for 4 weeks after starting drug and for 4 weeks after increasing dose.
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Now we conclude our episode number 96 “Tirzepatide.” Maria explained that tirzepatide has a dual effect on both GLP-1 and GIP receptors. The medication has been approved for the treatment of type 2 diabetes, but it has been proven to be very effective for weight loss also, almost comparable to bariatric surgery. Remember the contraindications and side effects of this medication to use it appropriately. The good news with tirzepatide is the cost —almost 3 times lower cost than its main competitor. Even without trying, every night you go to bed being a little wiser.
This week we thank Hector Arreaza and Maria Beuca.
Audio edition: Suraj Amrutia. Thanks for listening to Rio Bravo qWeek Podcast. If you have any feedback, contact us by email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week!
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References:
Dockrill, Peter. “Experimental Drug Breaks Record for Weight Loss in Latest Clinical Trial Results.” ScienceAlert, 9 May 2022, https://www.sciencealert.com/experimental-drug-breaks-record-for-weight-loss-in-latest-clinical-trial-results.
Frías, Juan P., et al. “Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes: Nejm.” New England Journal of Medicine, 5 Aug. 2021, https://www.nejm.org/doi/full/10.1056/NEJMoa2107519.
“Label as Approved by FDA. - Pi.lilly.com.” Mounjaro Prescribing Information, Lilly USA, LLC, May 2022, https://pi.lilly.com/us/mounjaro-uspi.pdf.
Mounjaro. Prescribing Information. Lilly USA, LLC. May 2022. https://pi.lilly.com/us/mounjaro-uspi.pdf?s=pi
