Should the 1 mL retatrutide pen be allowed to reach room temperature before subcutaneous administration, or can it be injected directly from the refrigerator?

Retatrutide Temperature Before Injection

You should allow the 1 mL retatrutide pen to reach room temperature for 30–60 minutes before injecting it, rather than administering it cold directly from the refrigerator. 1

Why Warming Is Recommended

Warming retatrutide to ambient temperature (approximately 15–30°C or 59–86°F) before injection provides several important clinical benefits:

• Markedly reduces injection-related pain compared with injecting a cold solution directly from the refrigerator 1
• Lowers the risk of lipodystrophy (abnormal fat distribution at injection sites), which can develop with repeated cold injections 1
• Optimizes molecular stability and absorption, supporting consistent therapeutic effect 1

These recommendations for retatrutide mirror established guidelines for other injectable medications like insulin and GLP-1 receptor agonists, where cold injections have been shown to cause local irritation and contribute to tissue changes at injection sites. 2, 3

Proper Warming Protocol

The correct warming procedure is straightforward:

• Remove the retatrutide pen from the refrigerator and leave it at room temperature for 30–60 minutes before injection 1
• The medication can be gently rolled between the palms to facilitate warming 2
• Never use direct heat sources such as microwaves, hot water, heating pads, or other accelerated warming methods, as these can degrade the medication 1

Storage Requirements

While the medication is warming, keep these storage principles in mind:

• Unopened retatrutide must be refrigerated at 2–8°C (36–46°F) and never frozen, as freezing can alter the drug's molecular structure and reduce efficacy 1
• Keep the medication away from direct sunlight, heat sources, and excessive agitation during storage 1
• If room temperatures exceed 30°C (86°F), return the medication to refrigeration after warming and before the next dose 2, 1

Pre-Injection Safety Checks

Before administering the warmed retatrutide, always perform these visual inspections:

• Check for any clumping, frosting, precipitation, or changes in clarity or color—any such abnormalities mean the product should not be used 1
• Verify the expiration date; expired retatrutide should be discarded 1
• Ensure the injection site is clean and dry to minimize infection risk 1

Common Pitfalls to Avoid

Several mistakes can compromise medication quality or increase injection discomfort:

• Do not inject cold retatrutide directly from the refrigerator, as this causes unnecessary pain and may contribute to lipodystrophy development 1, 3
• Avoid storing retatrutide in refrigerator doors due to temperature fluctuations from frequent opening and closing 1
• Never use frost-free freezers where temperature cycling can compromise drug integrity 1
• Do not rush the warming process with artificial heat sources 1

Supporting Evidence from Related Medications

The recommendation to warm injectable medications before administration is well-established across multiple drug classes. For insulin and other GLP-1 receptor agonists, guidelines consistently recommend allowing refrigerated medications to reach room temperature before injection to limit local irritation. 2, 3 Pending further retatrutide-specific studies, patients should follow these established recommendations for injectable therapies regarding temperature management. 2