Why Injection Site Matters for GLP-1 Medications

We have spent a lot of time exploring “glucagon-like peptide-1 receptor agonists” (GLP-1 agonists); please visit my previous articles for a refresher. We have covered how these medications work, including their side effects. Now, I want to discuss the actual method of administration in detail with you. 

Understanding Absorption: Subcutaneous vs. Intramuscular Injection

All GLP-1 injectables are administered via subcutaneous injection, but what does that mean?! Human skin is composed of three main layers. The outer layer is the epidermis, the middle layer is the dermis, and the third layer is the subcutaneous layer or hypodermis. Technically, there are many sublayers within each layer, but we do not need to get into that. Under the subcutaneous layer is muscle. When someone is getting a subcutaneous injection, it simply means the medication is being injected into the third layer, the subcutaneous layer, and not deeper into the muscle. If the injection is deeper, it is then called an intramuscular injection. The depth of the injection is determined by the length of the needle. The autoinjectors or syringes and needles provided with the GLP-1 medications will be for the correct length to ensure a subcutaneous injection.

Best Practices for GLP-1 Injection Placement

The four common subcutaneous injection sites are the abdomen, thighs, back of the upper arms, and upper buttocks. Some general tips include not injecting into or near scar tissue. Always make sure you use the correct needle, clean the area with alcohol, and allow it to dry (do not blow on it!) for about 10-15 seconds before inserting the needle. Make sure the area has enough fat underneath for the medication to absorb into. It is unnecessary to pinch the skin when injecting, this is sometimes recommended if there is a concern about injecting into muscle instead of fat. Always use a clean new needle! 

An important aspect of care when taking a medication that must be regularly injected subcutaneously is to rotate the injection sites. If this is not done, skin-related adverse reactions may develop. The most common of these is a type of lump that can form under the skin, called lipohypertrophy, made out of a thickened, hardened combination of fatty (adipose) tissues and fibrous tissues that form when an area is repeatedly injected into. Prevention is simple by rotating sites for repeated injections. This can mean rotating sides of the body if you prefer one site, for example, the abdomen, or rotating sites, for example, the abdomen, the upper arm, etc. Rotating sites does not have to be a large change in location, a difference of ½ inch is enough.

Some people are more sensitive than others to injections, and different techniques may be of benefit to decrease any discomfort. Some people use a combination of applying a cold pack to numb the skin for five minutes prior to the injection, a vibration device at the injection site when injecting, or a slightly pinching sensation close to the injection site, which can be done with a clothes pin or even your non-injecting hand. Some people find applying a warm, moist cloth or massaging over the injection site with your clean hand helps to decrease any discomfort from the injection. However, keep in mind that applying heat or massage may increase the absorption rate of medication.

Common Injection Sites: Abdomen, Thighs, and Upper Arms

The abdomen is the most used injection site, likely due to its ease of access, greater surface area, and usually less pain than other sites. It may be injected anywhere above the pelvic bones and below the rib bones. The needle should stay away from the belly button by about two inches, from the “love handle” area on each side and all the way across the front. The abdomen generally has the fastest absorption rate of the various sites. 

The thighs are often the second choice for subcutaneous injections; again, they are easy to access and have a large surface area. The front, or top if you are seated and the sides of the thighs are easily accessible areas for self-injection. The area to inject into is from the middle of the thigh around to the outside. Technically, you can inject into the back of the thighs, but this area is difficult to see and access for self-injection. The injectable area starts about three finger widths above the knee up to about one hand width below the hip joint. This area is generally less painful than other sites. Avoid the inner thigh, as this area has increased surface blood vessels. However, some individuals feel discomfort after injections in the thigh if walking or running afterward. When injected in the thighs, medication enters the bloodstream less quickly than in the abdomen or arms. However, this absorption rate may increase if you engage in exercise that uses the thigh muscles.

The back of the upper arms is also a viable injection site. However, for many people, self-injection into this site is more difficult. One technique is to rest the arm you will be injecting into along the back of a chair while seated so that it is still below your eye line. Then, pivot your body slightly so that you can reach the injection site with the opposite hand. The injection should be placed in the tricep area at the back of the upper arm. Starting about three finger widths above the elbow and below the shoulder joint. Medication is absorbed into the bloodstream faster than in the thighs or buttocks but slower than an injection into the abdomen. Again, exercise using the upper arm muscles may increase this rate of absorption.

The buttocks area is another potential injection site. This site is the most difficult for self-injection. But, for individuals with a needle phobia who may have someone else injecting them or who are having increased side effects, this may be the best option. The area where the injection should be placed is easiest to visualize if you think of the buttock area and then divide it with a line across into an upper and lower part and the gluteal cleft (that’s the “official term” for your butt crack) as the line dividing it left from right. The injection should be placed in the upper part of the outer half of each buttock, at least four finger widths away from the gluteal cleft. The buttocks allow medication to enter the bloodstream slowest of any of the subcutaneous injection sites.

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