Episode Details

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,