Session: Retatrutide (LY3437943), a Novel GIP/GLP-1/Glucagon Receptor Triagonist—Obesity, NAFLD, and T2D Phase 2 Trial Results
Speakers at this ADA Scientific Sessions presentation included: Lee Kaplan, MD, Ph.D. (The Obesity and Metabolism Institute), Matthias Tschöp, MD (Helmholtz Zentrum München), David D’Alessio, MD (Duke Division of Endocrinology), Arjun J. Sanyal, MD (Virginia Commonwealth University), Julio Rosenstock, MD (Director of the Dallas Diabetes Research Center at Medical City and Clinical Professor of Medicine on the University of Texas Southwestern Medical Center) and Ania M. Jastreboff, MD, Ph.D. (Associate Professor, Yale University).
This panel of experts presented exciting research for a brand new medication that could possibly be used for diabetes management. Here’s what it is advisable learn about Retatrutide now, so you may confer with your providers if it becomes available!
Retatrutide, the brand new kid on the block
Retatrutide is an experimental, once-weekly injectable medication that’s currently in phase 2 of clinical trials.
It’s a single peptide that targets the receptor of three hormones: glucagon, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). It just isn’t yet approved by the Food and Drug Administration (FDA).
Unlike other GIP/GLP-1 receptor agonist medications like Mounjaro or GLP-1 receptor agonist medications like Ozempic—this medication is the primary of its kind to also goal glucagon.
Leveraging using three hormones
Dr. D’Alessio discussed that utilizing GIP, GLP-1 and glucagon receptor triagonists together has impactful advantages for individuals with type 2 diabetes (T2D).
Targeting glucagon doesn’t only impact blood sugar levels. A chronic infusion of glucagon may also end in suppressed appetite. Activating glucagon may need useful effects on energy balance (satiety and weight maintenance).
Dr. D’Alessio suggests that contrary to popular belief, giving a glucagon agonist to patients has the potential to greatly improve health. High levels of glucagon enhance insulin secretion and reduces how briskly the body uses up that insulin. Adding glucagon to a GLP-1 can assist by:
- Causing more energy for use (calories)
- Not leading to higher blood sugars
- Improving weight reduction and suppressing appetite
- Improving lipids, triglycerides and levels of cholesterol
- Improving liver health
Phase 2 trial efficacy and safety results
The phase 2 trial consisted of 338 participants, all adults from ages 18-75 with either a body mass index (BMI) over 35, or over 27 with one other chronic health condition—hypertension or type 2 diabetes.
The phase 2 study checked out the differences between weekly injections of retatrutide versus a placebo over a 48-week trial. Doses of retatrutide were evaluated at 1 mg, 4 mg, 8 mg, and 12 mg.
Effects on obesity
Dr. Jastreboff shared that participants within the study saw remarkable leads to weight reduction. At 24 weeks (halfway through the study), participants lost a mean of 17.9% of their body weight on 12mg of retatrutide weekly.
At 48 weeks, participants on the weekly 12mg dose lost a mean of 24.2% of their total body weight. Which means the typical participant on the very best dose of the medication lost a few quarter of their body weight at 11 months.
The common weight reduction was 58 kilos, and weight reduction continued even after the study ended and the medication stopped. 100% of study participants lost no less than 5% of their body weight on the 8 mg and 12mg retatrutide doses. Women on average lost more weight than men.
These initial results show that it is a more powerful medication than anything currently available on the market for weight reduction. On condition that people living with T2D are continually told to “just drop some weight” but are never given support or the tools needed to assist achieve any weight reduction goals, retatrutide has the potential to assist many individuals.
Effects on NAFLD
Dr. Sanyal showed that non-alcoholic liver fat was lowered on all doses of the retatrutide versus the placebo.
80% or more of participants on each the 8mg and 12 mg doses had a greater than 70% relative reduction in liver fat. The impacts of retatrutide on NAFLD proved to be dose-dependent, with 86% of participants on the 12 mg weekly dose resolving their hepatic steatosis at week 48.
Moreover, the medication improved lipid and blood pressure levels at 48 weeks.
Effects on T2D management
Individuals with obesity and diabetes typically have a harder time losing a few pounds than individuals with obesity and no diabetes. Nevertheless, within the study, retatrutide helped improve each blood sugars levels and resulted in significant weight reduction.
Dr. Rosenstock showed the next improvements in blood sugar levels were seen:
- Average A1C at baseline was 8.3% and was reduced to six.1% with the 12 mg dose at 36 weeks.
- The common A1C reduction was 0.45%, with 76% of participants achieving higher A1C outcomes.
- A1C of <6.5% was achieved in as much as 82% of study participants.
- A1C of <5.7% was achieved in as much as 31% of study participants.
Hostile unintended effects
As with many medication, even retatrutide showed some not-so-great unintended effects. Between 73-90% of the study participants experienced antagonistic unintended effects, including gastrointestinal issues, nausea, vomiting, diarrhea, constipation, fatigue, early satiety and decreased appetite.
Nevertheless, the unintended effects were largely mild to moderate, and went away over the duration of study. TRIUMPH phase 3 trials are actually underway with the hope of FDA approval soon.
These are exciting study results which have the potential to transform the health outcomes of people that live with NAFLD, obesity and kind 2 diabetes. At Beyond Type 2, we’re committed to following these advancements to maintain the community informed, so be sure that to enroll in our newsletter and follow our news coverage for retatrutide updates!