Researchers might still be navigating the nuances of the appropriate retatrutide dosage for their studies, considering how novel the peptide is.

This peptide is still under clinical investigation, but the data already shows promising potential for managing obesity and improving metabolic health due to its unique mechanism of action.

Emerging research highlights its efficacy at therapeutic doses in:

• Reducing body weight and altering body composition.
• Enhancing metabolic parameters, including glucose and lipid metabolism.
• Improving liver health and cardiovascular parameters.

To fully leverage retatrutide's therapeutic potential, it's imperative for researchers to be well-informed about the most recent evidence on dosing and safety strategies.

In this overview, we aim to provide researchers with a retatrutide dosage calculator informed by the latest clinical trials. Additionally, we offer guidance on sourcing research-grade retatrutide, ensuring that studies are conducted according to the highest scientific standards.

What is Retatrutide | Overview

Retatrutide (LY3437943) is an innovative peptide under development by Eli Lilly for therapy in overweight, obesity, and type 2 diabetes (T2D).

Functioning as a triple-agonist, the peptide has the ability to simultaneously engage with three key receptors: glucagon (GCGR), as well as the receptors for the incretin hormones GLP-1 (GLP-1R) and GIP (GIPR) [1].

This compound is a 39-amino-acid, single-chain peptide, meticulously crafted from a GIP peptide structure to facilitate triple agonist capabilities. It primarily favors GIPR activation, while its influence on GLP-1R and GCGR is moderately less pronounced [1].

Here is what researchers should know about these receptors:

• GIPR (Glucose-Dependent Insulinotropic Polypeptide Receptor) is found in the pancreas, adipose tissue, and the brain, among other organs. The hormone activating these receptors plays a role in regulating insulin synthesis, appetite regulation, and fat metabolism [2].
• GLP-1R (Glucagon-Like Peptide-1 Receptor) is found in the pancreas, adipose tissue, heart, digestive system, and brain, among other organs. The hormone targeting them plays a role in insulin synthesis, gastric emptying, and appetite regulation [3, 4].
• GCGR (Glucagon Receptor) is found in liver and adipose tissues, among other organs. Glucagon plays a role in preventing hypoglycemia regulating fat metabolism and overall metabolic rate [5].

Early-phase clinical studies, specifically phase 1b, indicate that retatrutide exhibits promising pharmacokinetic properties, enabling its administration through subcutaneous injection once every week [6].

Further exploration in phase 2 clinical trials has demonstrated the compound's safety and substantial efficacy in enhancing metabolic health and facilitating weight reduction [7, 8].

Eli Lilly is actively pursuing the potential of retatrutide against obesity through its TRIUMPH phase-3 clinical program. The program encompasses four ongoing trials (TRIUMPH 1-4), all in the participant recruitment stage [9].

Retatrutide Dosage Chart | Quick Breakdown

Timeline	Weeks 1-4	Weeks 5-8	Weeks 9-12	Weeks 13-(full dose)
Retatrutide Weight Loss Dose for Research [1x weekly]	2mg	4mg	8mg	12mg

Recommended Dosage for Retatrutide Research

Drawing from extensive clinical trial data, retatrutide has demonstrated several advantages when dosed properly in research trials. 

Specifically, its efficacy is highlighted in areas such as weight management, blood sugar control, and effects on metabolic health.

Retatrutide Dosage for Weight Management Research

Currently, there is only one published clinical trial on retatrutide dosed specifically for weight loss. It is a 48-week phase 2 trial in 338 non-diabetic adults with overweight and obesity [8].

The participants were split into 6 groups receiving the following dosages:

• 1mg/weekly for 48 weeks
• 2mg/weekly for 4 weeks, then 4mg/weekly for 44 weeks
• 4mg/weekly for 48 weeks
• 2mg/weekly for 4 weeks, 4mg/weekly for another 4 weeks, then 8mg/weekly for 40 weeks
• 4mg/weekly for 4 weeks, then 8mg/weekly for 44 weeks
• 2mg/weekly for 4 weeks, 4mg/weekly for another 4 weeks, then 8mg/weekly for 4 weeks, and 12mg/weekly for 36 weeks

The researchers reported dose-dependent effectiveness, reaching a -8.7% weight reduction in the 1mg/weekly group, -17.1% in the 4mg/weekly groups, -22.8% in the 8mg/weekly groups, and -24.2% in the 12mg/weekly group, versus -2.1% in the placebo group.

Moreover, 100% of the participants in this trial receiving a maximum dose of 8mg/weekly or 12mg/weekly lost at least 5% of their initial body weight. There were also reductions in waist circumference, blood pressure, glycated hemoglobin, fasting glucose, insulin, and lipid levels (except HDL cholesterol) [8].

Currently, the ongoing TRIUMPH 1 trials aim to confirm and build on these results, as it aims to test the effectiveness of the peptide in 2100 non-diabetic individuals for a total of 89 weeks [10].

Retatrutide Dosage for Diabetes Research

Retatrutide has been dosed for diabetes in phase 1b and phase 2 trials, with phase 3 trials currently being underway. 

The researchers have investigated its effectiveness regarding the reduction of glycated hemoglobin (HbA1c) which is a major indicator for glycemic control in T2D.

The phase 1b trial lasted just 12 weeks and involved the five retatrutide groups based on dosage, each with a unique effectiveness profile [11]:

• 0.5mg/weekly – no difference compared to placebo
• 1.5mg/weekly – HbA1c improved by -1.2% from baseline; mean body weight dropped by -2.4kg
• 3mg/weekly – HbA1c improved by -1.7% from baseline; mean body weight dropped by -4.7kg
• 3mg/weekly for 4 weeks followed by 8 weeks of  6mg/weekly – HbA1c improved by -1.9% from baseline; mean bodyweight dropped by -7.8kg
• 3mg/weekly and 6mg/weekly for 2 weeks each followed by 9mg/weekly and 12mg/weekly for 4 weeks each  – HbA1c improved by -1.6% from baseline; mean bodyweight dropped by -9kg

The phase 2 trial lasted for 36 weeks and included 281 T2D patients [7]:

• 1mg/weekly for 36 weeks
• 2mg/weekly for 4 weeks, then 4mg/weekly for 32 weeks
• 4mg/weekly for 36 weeks
• 2mg/weekly for 4 weeks, 4mg/weekly for another 4 weeks, then 8mg/weekly for 28 weeks
• 4mg/weekly for 4 weeks, then 8mg/weekly for 32 weeks
• 2mg/weekly for 4 weeks, 4mg/weekly for another 4 weeks, then 8mg/weekly for 4 weeks, and 12mg/weekly for 24 weeks

The highest dosage group (12mg/weekly) saw greater improvement in both HbA1c and body weight. The participants in this group had a mean -2.16% reduction in HbA1c levels and lost -16.94% of their baseline weight.

Further, the slow escalation group reaching 8mg/weekly saw greater improvements in HbA1c and body weight compared to the group reaching 8mg/weekly after just 4 weeks [7].

Currently, a phase 3 trial (TRIUMPH-2) aims to investigate the effectiveness of 89 weeks of retatrutide therapy in 1000 T2D patients who are overweight or obese. The exact dosing protocol to be used in this trial is not published [12].

Retatrutide Dosage for Other Research Objectives

Retatrutide is currently under investigation for weight loss in other medical conditions, such as cardiovascular and orthopedic conditions. Specifically, Eli Lilly has initiated the following studies alongside TRIUMPH-1 and TRIUMPH-2:

• TRIUMPH-3: A 113-week study estimated to enroll 1300 participants. The trial will investigate retatrutide therapy effectiveness in overweight or obese individuals with a history of heart attack, stroke, or peripheral arterial disease [13].
• TRIUMPH-4: A 77-week study aimed to examine the effectiveness of retatrutide therapy in 405 overweight or obese individuals with knee osteoarthritis [14].

Unfortunately, the dosing protocols in these phase 3 trials are not yet published, but the most likely protocol to be used will likely involve the following dosing regime:

• 2mg/weekly for 4 weeks, 4mg/weekly for another 4 weeks, then 8mg/weekly for 4 weeks, and 12mg/weekly for the remainder of the trial period.

Retatrutide Dosage Calculator

Researchers must follow specific recommendations when dosing retatrutide injections in experimental settings and studying its weight loss effects [7, 8].

Retatrutide must be dosed carefully, as the dose must be increased gradually to minimize side effects. 

A typical starting dose for the first four weeks in phase 2 trials is 2mg/week. The gradual increase in dosage must last for at least 12 weeks.

The maximum recommended dosage of retatrutide in research settings is up to 12 mg/week. Designed for once-weekly administration, it can be administered at any time of the day, with or without meals. 

To date, retatrutide has been evaluated in clinical trials for periods extending up to 48 weeks. Longer trials, lasting up to 113 weeks, are expected to be published in 2026.

Here is a sample dosing guide based on the available data [7, 8]:

• Retatrutide Dose: Initiated at 2mg/weekly for the first four weeks of the study period, followed by an increase to 4mg/weekly in weeks 5-8, 8mg/weekly in weeks 9-12, 12mg/weekly in weeks 13 and beyond.
• Frequency: Once weekly; subcutaneously.
• Study Duration: up to 48 weeks.
• Notes: Dosage should never exceed 12mg/weekly. Missed doses should be administered within 5 days or skipped, and consequent doses should taken according to the initial schedule

Retatrutide Benefits | Overview

As mentioned, the available phase 1b and phase 2 trials report that the peptide is highly effective for weight loss and improved glycemic control in T2D. 

Moreover, a substudy of one of the phase 2 trials also reports that the peptide is highly effective for reducing liver fat in people with obesity who also have metabolic-dysfunction-associated steatohepatitis (MASH).

Here are more details regarding the most notable benefits:

• The phase 1b and phase 2 trials in T2D patients reported that retatrutide reduced triglycerides, non-HDL cholesterol, and other cardiometabolic parameters compared to baseline. The improvements were greater compared to both dulaglutide and placebo [7, 11].
• The 24.2% weight loss reported by the 48-week phase 2 trial in 338 non-T2D patients reported that 12mg/weekly retatrutide therapy is the highest weight loss reported by a pharmacological agent in a clinical trial. The majority of participants lost at least 10% of their initial weight, with almost two-thirds losing 20% or more, nearly half losing 25% or more, and about a quarter losing 30% or more [8].
• This 48-week phase 2 trial also focused on a subgroup of 98 patients with at least 10% liver fat (assessed via MRI) and a MASH diagnosis. The 12mg/weekly retatrutide therapy resulted in an average reduction of 82.4% in liver fat within the first 24 weeks, whereas the placebo group showed no change. Additionally, 86% of these patients reached normal liver fat levels (<5%). There were also decreases in inflammation markers, liver enzymes, triglyceride levels, and insulin resistance [15].

Retatrutide Side Effects | Overview

Retatrutide has not been explored in phase-3 studies or received approval for human use as of 2024. The forthcoming TRIUMPH phase-3 clinical program is set to offer comprehensive insights into the efficacy and safety profile of retatrutide.

However, existing data from phase 2 trials indicate that the rate of side effects associated with retatrutide aligns with those observed for other incretin mimetics such as the FDA-approved dulaglutide [7, 11].

One of the phase 2 trials which compared retatrutide to dulaglutide reported that within 36 weeks of therapy, 12mg/weekly retatrutide led to side effects in 76% of subjects, compared to 67% for the GLP-1 agonist. The incidence of serious side effects was also similar [7]. 

The largest of the two most notable trials, included 338 non-diabetic subjects 6% to 16% of which dropped out from the study due to side effects, depending on the retatrutide dose. In comparison, there were no dropouts due to adverse events in the placebo group [8]. 

The most common reasons for discontinuing treatment were gastrointestinal adverse events. Here is a list of the most common adverse events experienced by the 62 people who received the highest 12mg/weekly dose of the peptide:

• Nausea: 28 participants (45%)
• Vomiting: 12 (19%)
• Constipation: 10 (16%)
• Diarrhea: 9 (15%)
• Cardiac arrhythmia: 7 (11%)
• Fatigue: 6 (10%)
• Early satiety: 6 (10%)
• Increase in lipase level: 5 (8%)
• Injection-site reaction: 5 (8%)
• Hepatic disorder: 2 (3%)
• Pancreatitis: 1 (2%)

Here is what researchers should know about the risk of more serious side effects [7, 8]:

• Fifteen serious adverse events occurred in 13 participants, with a similar frequency in both the retatrutide and placebo groups (4%). 
• Transient increases in alanine aminotransferase (ALT) levels to more than three times the upper limit were observed in 1% of retatrutide recipients. 
• There were asymptomatic increases in amylase and lipase levels, except for one case of acute pancreatitis in the highest dose group.

These findings highlight the importance of careful dose management and monitoring for adverse events in the research use of retatrutide.

Safety Considerations and Contraindications

Retatrutide is under clinical development as part of the TRIUMPH program, which aims to provide comprehensive data on its efficacy and safety. The program's findings could support the potential approval of retatrutide for medical use [9]. 

However, the peptide is currently unapproved for human use and researchers must carefully consider the risks associated with using retatrutide in laboratory settings, emphasizing the need for professional oversight during its handling and experimentation.

One common concern with previous GLP-1 agonists and GLP-1/GIP agonists has been the risk of medullary C-cell carcinoma of the thyroid gland.

While this risk has been observed in mice studies, it is important to note that no cases of this type of thyroid cancer or any other malignancy have been reported in humans, despite the widespread use of GLP-1 agonists over the past decade.

Nevertheless, a history of thyroid cancer is considered to be one of the contraindications against participating in retatrutide trials, such as the one in the TRIUMPH program [9].

Other contraindications include pregnancy and lactation. Animal studies suggest this could be problematic, although these findings also have not been confirmed in human studies.

Where to buy Retatrutide online? | 2024 edition

Many online vendors offer retatrutide, providing researchers with numerous options.

However, not all vendors are legitimate, To ensure you receive high-quality retatrutide, it is recommended to use only vetted sources.

Our peptide review team has evaluated multiple vendors by purchasing retatrutide, and the following consistently meets high standards for peptide purity, delivery, and customer support.

Polaris Peptides

Polaris Peptides is a newer peptide source supplying high-quality peptides designed exclusively for research and development endeavors of professionals. The vendor offers several key benefits, including:

• Transparency: Detailed lab results accompany every Polaris peptide for sale, providing you with the assurance of retatrutide’s quality and integrity. 
• Purity and Precision: Polaris retatrutide for sale is crafted with the utmost precision, ensuring a purity level of over 99%.
• Customer Support: Polaris Peptides is committed to providing fast shipping and personalized support, ensuring a seamless purchasing experience