Retatrutide Side Effects
Tuesday, March 26th, 2024

Retatrutide is a potential triple agonist of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and glucagon receptors (1). Developed by Eli Lilly and the company, Retatrutide is aimed to be one of the most effective weight loss medications.

The unique mode of action allows Retatrutide to be used for chronic weight management while concomitantly improving glycemic control.

While it is still under phase iii clinical trials, and waiting for FDA approval, there are promising results published in the New England Journal of Medicine (NEJM) (2). Data show that Retatrutide causes substantial weight reduction in the participants with higher body mass index (BMI).

Not only this, consistent use of the peptide by the participants has been shown to significantly mitigate the risk of cardiovascular disease.

While trial results are considerably in favor of Retatrutide, it is worth mentioning that no pharmacological intervention is safe enough to not cause any adverse effects. Understanding and mitigating these adverse reactions are paramount for safe and effective patient care.

Gastrointestinal Disturbances:

gastrointestinal disturbances - Retatrutide Side Effects

Among the most commonly reported adverse effects of Retatrutide are nausea and vomiting, which can range from mild to severe in intensity. These symptoms typically manifest shortly after administration and may persist for varying durations.

Retatrutide administration may also precipitate diarrhea, characterized by loose stools and increased frequency of bowel movements. Dehydration and electrolyte imbalances are potential complications of severe diarrhea.

Dermatological Reactions:

dermatological reaction - Retatrutide side effect

A notable dermatological adverse effect of Retatrutide is the development of skin rash, presenting as erythematous or pruritic lesions. In some cases, the rash may be accompanied by itching or burning sensations, warranting prompt medical evaluation.

Rarely, Retatrutide may elicit severe hypersensitivity reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, characterized by extensive skin detachment and mucosal involvement. These reactions constitute medical emergencies and require immediate cessation of Retatrutide therapy and appropriate supportive measures.

Cardiovascular Effects:

ecg - retatrutide side effect

Retatrutide administration has been associated with transient episodes of hypotension, particularly during the initial phases of therapy. Patients with pre-existing cardiovascular conditions or those receiving concomitant antihypertensive medications may be at increased risk.

Rare instances of cardiac arrhythmias, including tachycardia or bradycardia, have been reported following Retatrutide administration. Close monitoring of cardiac function is warranted in susceptible individuals.

Metabolic Disturbances:

Metabolic disturbances through retatrutide

Retatrutide may induce transient increases in blood glucose levels, particularly in individuals with underlying diabetes mellitus or impaired glucose tolerance. Regular monitoring of blood glucose levels is essential during Retatrutide therapy.

Imbalances in electrolyte levels, including hyponatremia or hyperkalemia, may occur as a consequence of Retatrutide therapy. Close monitoring and appropriate supplementation are essential to prevent complications.

Respiratory Complications:

Respiratory Complications

Some individuals may experience dyspnea or respiratory distress following Retatrutide administration, possibly due to bronchoconstriction or pulmonary edema. Prompt assessment and intervention are imperative to alleviate symptoms and prevent respiratory compromise.

Neurological Symptoms:

Headache is a frequently reported adverse effect of Retatrutide, often transient and mild in nature. However, persistent or severe headaches warrant further evaluation to rule out underlying intracranial pathology.

Retatrutide may precipitate episodes of dizziness or lightheadedness, potentially compromising patient safety, especially during activities requiring concentration or coordination.

While Retatrutide offers least health risks and is generally seen as a safe weight loss drug compared to other weight loss medications, it is important to symptomatically manage the patients in case of any adverse effects experienced after the weekly injection of Retatrutide.


  1. Urva, S., Coskun, T., Loh, M. T., Du, Y., Thomas, M. K., Gurbuz, S., Haupt, A., Benson, C. T., Hernandez-Illas, M., D’Alessio, D. A., & Milicevic, Z. (2022). LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet (London, England), 400(10366), 1869–1881.
  2. Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML; Retatrutide Phase 2 Obesity Trial Investigators. Triple-Hormone-Receptor Agonist Retatrutide for Obesity – A Phase 2 Trial. N Engl J Med. 2023 Jun 26. doi: 10.1056/NEJMoa2301972. Epub ahead of print.

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