Retatrutide

1. Retatrutide and Obesity

Retatrutide (LY3437943) is a synthetic peptide agonist. To be more precise, it is a Triple Agonist that activates three key receptors for metabolism and energy balance: Glucagon, GIP, GLP-1. These receptors are crucial for regulating blood sugar, appetite and metabolism.

Obese adults were randomly assigned to receive Retatrutide (1, 4, 8 or 12 mg) and a placebo once weekly for 48 weeks in a Phase 2 clinical trial published in The New England Journal of Medicine (2023;389:514-526). ¹ At 24 weeks, people taking Retatrutide lost from 7% to 17% of their body weight, while those taking placebos lost only 1.6%.

• Weight loss continued at 48 weeks, and longer durations might result in greater weight loss. ¹
• Almost 93% of those in the 12 mg group lost at least 10 percent of their body weight, and 83 percent lost at least 15 percent. ¹
• Weight loss was further sustained after 48 weeks: 8.7% (1 mg), 17.1% (4 mg), 22.8% (8 mg), and to 24.2% (12 mg) while  2.1% for placebo. ¹

Figure 1. Average change in body weight over 48 weeks in participants receiving Retatrutide compared to placebo (adapted from NEJM 2023)

2. Heart Health and Metabolic Effects

In addition to its role in weight loss, Retatrutide was observed to have beneficial effects on several health indicators. The levels of better blood sugar and insulin were seen as early as 24 weeks.¹ Nearly 72 percent of study participants who started with prediabetes were back to normal blood sugar at 48 weeks, compared to around 22 percent of those assigned to the placebo. ¹ Better blood sugar and insulin were observed as early as 24 weeks. ¹ Many participants cut back or stopped their usual blood pressure medications (For instance, 41% in the 8-mg group stopped at least one). ¹ Furthermore, Cholesterol levels and waist size also improved across most dose groups.These results indicate a global effect of Retatrutide on multiple aspects of the body’s metabolism beyond weight reduction.

 3. Safety & Findings

Safety:

• No serious safety issues, such as hypoglycemia or thyroid problems, were reported in the study. ¹
• The percentage of participants who had side effects ranged from 73% to 94% in the Retatrutide groups and was 70% in the placebo group. ¹
• Nausea, diarrhea, vomiting and constipation were the most frequent effects that were dose-related and mainly mild to moderate. ¹
• Modest increases in heart rate were observed early in the trial and attenuated after 48 weeks. ¹

Findings:

• Generally, those participants with the higher BMI values had greater decreases in weight. ¹
• The researchers initially began patients on lower doses and then worked their way up to minimize side effects. ¹
• However, in certain groups, females lost more amount of weight compared with males. ¹

4. Research-Use-Only Notice 

Retatrutide is available for research purposes only. The information above summarizes results from published scientific studies. This product is not intended for human or medicinal use yet. Scientists should adhere to all local and federal regulations in working with and researching this compound.

¹ Jastreboff et al. “Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial.” New England Journal of Medicine, 2023; 389:514-526.