Retatrutide

What is retatrutide?

Retatrutide is an investigational once-weekly injectable drug currently being studied for the treatment of obesity and type 2 diabetes. It is a novel peptide with triple hormone receptor agonist activity, targeting the glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors. By activating all three receptors, retatrutide aims to deliver greater metabolic benefits than drugs targeting only one or two pathways.

How does retatrutide work?

① GLP-1 receptor activation:

● Increases insulin secretion: Retatrutide stimulates the pancreas to release insulin when blood glucose rises, aiding blood sugar regulation.

● Reduces glucagon secretion: Inhibits the release of glucagon (a hormone that raises blood sugar), thereby aiding better glycemic control.

● Suppresses appetite: Activating GLP-1 receptors in the brain decreases appetite and increases satiety, promoting weight loss.

● Slows gastric emptying: Delays the rate at which food leaves the stomach, helping prevent rapid postprandial blood sugar spikes.

② GIP Receptor Activation:

● Enhances insulin release: GIP synergizes with GLP-1 to stimulate glucose-dependent insulin secretion from the pancreas.

● Improves insulin sensitivity: It enhances the body’s insulin response, promoting better glucose uptake by tissues.

③ Activation of Glucagon Receptors:

● Increases Energy Expenditure: Activating glucagon receptors promotes the breakdown of stored fat (lipolysis) and stimulates heat production (thermogenesis), thereby increasing calorie burning.

● Weight Loss: By enhancing lipolysis and energy expenditure, retatrutide significantly reduces body weight beyond appetite suppression.

● Effects on the Liver: While glucagon can stimulate hepatic glucose production, Retatrutide’s balanced activation aims to mitigate adverse impacts on blood glucose levels.

Potential Health Benefits of Retatrutide

● Significant Weight Loss: Clinical trials demonstrate Retatrutide’s ability to achieve substantial weight reduction. Participants lost an average of 24% of their body weight over 48 weeks, outperforming existing weight-loss medications.

● Improved Glycemic Control: Retatrutide effectively lowers blood sugar levels, making it a promising treatment for type 2 diabetes. Studies show reduced glycated hemoglobin (HbA1c) levels in participants, indicating enhanced blood sugar management.

● Enhanced Cardiovascular Health: The drug is associated with improvements in cardiovascular risk factors, including reduced blood pressure and lipid levels. These changes help lower the risk of heart disease.

● Reduces liver fat: Retatrutide has demonstrated potential to decrease liver fat content, benefiting patients with non-alcoholic fatty liver disease (NAFLD). This effect may help slow the progression of liver-related conditions.

Potential Side Effects of Retatrutide

● Gastrointestinal issues: Common symptoms include nausea, vomiting, diarrhea, and constipation. These typically occur early in treatment and may diminish over time.

● Decreased appetite: While beneficial for weight loss, reduced food intake may be challenging for some individuals to manage.

● Potential hypoglycemia: Risk of low blood sugar exists, particularly when used with other glucose-lowering medications.

● Injection site reactions: Some trial participants reported mild to moderate reactions at the injection site, such as redness or irritation.

● Dizziness and headaches: These symptoms occurred in some trial participants, typically during the body’s adjustment to the medication.

● Potential gallbladder issues: As with other weight-loss medications, significant weight loss increases the risk of gallstones and other gallbladder-related conditions.

● Increased heart rate: Some participants reported accelerated heart rate, which may require monitoring, especially for those with a history of heart disease.

● Skin effects: Significant weight loss may lead to skin laxity and increased wrinkling. This is not unique to GLP-1 medications. Any factor causing substantial weight loss can exacerbate wrinkles and skin laxity, as the underlying supportive structures of the skin were stretched by excess weight. The heavier the initial weight, the more pronounced this effect during weight loss.

● If you experience intolerable nausea or vomiting, revert to your previous dose and wait several weeks before attempting to increase it again. You do not need to reach the maximum dose. If you are losing weight without significant side effects, you may maintain your current dose. If you develop severe constipation or abdominal pain, stop the medication and seek immediate care from your primary care physician (PCP) or emergency department. If you experience neck swelling or difficulty swallowing, see your primary care physician (PCP) or go to the emergency department.

Retatrutide Dosage Guidelines

Retatrutide is administered as a weekly subcutaneous injection. The starting dose is 1 mg weekly, with a maximum dose of 12 mg weekly. Very few patients require the maximum dose. The optimal dose is the amount that reduces weight without causing intolerable side effects. Dosing varies for each patient.

If you experience intolerable side effects such as nausea and vomiting, revert to your previous dose for one to two weeks before attempting an increase. If severe nausea or vomiting persists, maintain only the dose you can tolerate.