What are the most common complications of subcutaneous injections?

October 9, 2025 •

5 min read

Approximately 64% of people with diabetes will develop lipohypertrophy, a common complication from repeated injections, at some point in their life [1.4.3]. Understanding what are the most common complications of subcutaneous injections is the first step toward prevention and safe medication administration.

Quick Summary

This overview details the most frequent complications from subcutaneous injections, such as injection site reactions, lipohypertrophy, and infection. It explains causes, prevention strategies like site rotation, and when to seek medical care.

Key Points

Site Rotation is Key: Consistently rotating injection sites is the most effective way to prevent lipohypertrophy, a common complication where fatty lumps form under the skin [1.4.4].
Local Reactions are Common: The most frequent complications are mild injection site reactions like pain, redness, swelling, and bruising, which typically resolve on their own [1.2.3].
Lipohypertrophy vs. Lipoatrophy: Lipohypertrophy is a buildup of fat tissue from repeated injections, while lipoatrophy is a rare loss of fat tissue at the injection site [1.9.1, 1.9.3].
Infection is a Risk: Any break in the skin can lead to infection. Proper hygiene, including hand washing and using alcohol swabs and new needles, is crucial for prevention [1.2.2, 1.2.4].
Know When to Call a Doctor: Seek medical attention for signs of infection (fever, pus, spreading redness), severe pain, blistering, or any reaction that worsens significantly after 48 hours [1.10.5].
Never Reuse Needles: Using a new, sterile needle for every injection reduces pain, tissue damage, and the risk of infection and lipohypertrophy [1.4.1].
Impact on Medication Absorption: Tissue changes like lipohypertrophy can interfere with the absorption of medications like insulin, leading to poor glycemic control [1.4.4].

Subcutaneous injections are a common method for administering medications like insulin and anticoagulants into the fatty tissue layer between the skin and muscle [1.2.4]. While generally safe, this procedure carries a risk of complications, most of which are mild and localized [1.2.3]. Awareness and proper technique are critical in minimizing these adverse events.

Local Injection Site Reactions

The most frequent complications are local injection site reactions [1.2.3]. These are typically mild, self-limiting, and resolve within a few days [1.2.3].

Pain, Swelling, and Redness

Pain, redness (erythema), and swelling at the injection site are very common [1.2.4]. These reactions can be caused by the needle piercing the skin, the medication itself irritating the tissue, or inserting the needle at an improper angle [1.2.2, 1.7.2]. Most people feel a minor "pinch" during the injection [1.2.4]. Some medications are known to cause a burning or stinging sensation [1.2.2]. Applying ice to the area before injection or using a numbing cream can help reduce pain [1.2.2, 1.6.2].

Bruising and Bleeding

Minor bleeding and subsequent bruising (ecchymosis) are also common [1.2.4]. This happens when the needle nicks a small blood vessel on its way into the subcutaneous tissue [1.6.1]. Applying gentle pressure with gauze after withdrawing the needle can help prevent bruising, but rubbing the site should be avoided as it can worsen it [1.8.4, 1.6.1]. People with low iron or those taking blood thinners may be more susceptible to bruising [1.6.1].

Tissue and Skin Complications

Repeatedly injecting in the same location can lead to more significant tissue changes that can affect medication absorption and glycemic control in diabetic patients [1.4.4, 1.9.1].

Lipohypertrophy

Lipohypertrophy (LH) is a firm, rubbery lump of fatty tissue that develops under the skin due to repeated injections in the same spot [1.4.1]. This is the most common cutaneous complication of insulin therapy and is caused by the lipogenic (fat-forming) effect of insulin on fat cells [1.4.3, 1.9.3]. Injecting medication into an area of LH can lead to erratic or incomplete drug absorption, causing issues like hyperglycemia or hypoglycemia [1.4.1, 1.4.4]. The primary prevention and treatment for LH is strict rotation of injection sites, allowing the affected tissue to rest and heal for at least two to three months [1.4.1].

Lipoatrophy

Lipoatrophy (LA) is the localized loss of subcutaneous fat, creating a visible dent or hollow in the skin [1.5.2, 1.9.5]. It is considered a rare immunological side effect of insulin therapy [1.9.1]. In the past, LA was more common due to impurities in animal-derived insulins, but with the advent of modern human and analog insulins, it has become very rare [1.5.1, 1.9.1]. Treatment may involve avoiding the affected site and, in some cases, has responded to corticosteroid treatment [1.5.3, 1.5.5].

Infection and More Serious Complications

Though less common, more serious complications can occur and may require medical attention [1.2.1].

Infection

Any break in the skin creates an opportunity for bacteria to enter, which can lead to an infection [1.2.2]. Signs of a localized infection (cellulitis) include increasing redness that spreads, warmth, severe pain, pus or drainage, and fever [1.7.5]. An untreated infection can lead to a more serious abscess, which is a collection of pus under the skin that may require medical drainage [1.7.5]. The risk of infection is minimized by washing hands, cleaning the injection site with an alcohol swab before injecting, and always using a new, sterile needle for each injection [1.2.2, 1.2.4]. Reusing or sharing needles significantly increases infection risk [1.2.2].

Differentiating Common Injection Site Reactions

It is important for patients to distinguish between a normal, mild reaction and a developing complication that requires medical attention.


Feature	Mild Local Reaction	Lipohypertrophy	Infection (Cellulitis)
Appearance	Mild redness, slight swelling, possible bruising [1.2.3, 1.7.3]	Raised, firm, rubbery lump under the skin; skin may appear normal or shiny [1.4.1, 1.4.5]	Spreading redness, significant swelling, possible red streaks, pus, or blistering [1.7.5]
Sensation	Minor pain, itching, or tenderness that resolves in 1-2 days [1.2.2]	Often numb or has less sensation; can feel like a hard knot [1.4.1, 1.4.3]	Increasing pain, tenderness, and warmth at the site [1.7.4, 1.7.5]
Onset & Duration	Occurs shortly after injection; lasts 1-3 days [1.7.2]	Develops over weeks to months of repeated injections in the same area [1.4.2]	Can develop 24-48 hours or more after injection; worsens over time [1.10.1, 1.7.5]
Systemic Signs	None	None	May be accompanied by fever, chills, and feeling unwell [1.7.5]

Best Practices for Prevention

Following proper injection technique is the best way to prevent complications.

Site Rotation: This is the most crucial step to prevent lipohypertrophy [1.4.4]. Rotate between different body areas (abdomen, thighs, upper arms, buttocks) and also rotate within each area, keeping injections at least one inch apart [1.8.1, 1.8.3]. Keeping a chart or using an app can help track sites [1.4.1].
Use New Needles: Never reuse needles. A fresh needle is sharper, causes less pain and tissue damage, and minimizes infection risk [1.4.1, 1.6.1].
Proper Hygiene: Always wash hands with soap and water and clean the selected site with an alcohol swab before injecting [1.2.4].
Correct Technique: Pinch a fold of skin and insert the needle at a 90-degree angle (or 45 degrees if you have very little body fat) [1.8.4]. Inject the medication slowly and steadily [1.8.4].

When to See a Doctor

You should contact a healthcare provider if you experience symptoms that suggest a more serious complication [1.10.5]. Seek medical attention if you notice:

Severe pain, swelling, or blistering at the injection site [1.10.5].
Redness that is larger than 2 inches, spreads, or worsens after 48 hours [1.10.1, 1.10.2].
Signs of infection like pus, drainage, or red streaks spreading from the site [1.7.5].
A fever of 100.4°F (38°C) or higher [1.7.4].
Symptoms of a severe allergic reaction (anaphylaxis), such as difficulty breathing, swelling of the face or throat, or widespread hives, which require immediate emergency care (Call 911) [1.10.5].

Conclusion

While subcutaneous injections are a vital and routine part of treatment for many conditions, they are not without potential complications. The most common issues are minor and localized, such as pain, bruising, and redness. However, more significant problems like lipohypertrophy and infection can arise, particularly with poor technique or inadequate site rotation. By adhering to best practices—especially rotating injection sites and using a new needle for every dose—patients can significantly reduce their risk of complications, ensure effective medication absorption, and maintain their long-term health. Regular skin inspection and communication with a healthcare provider about any persistent or concerning reactions are essential for safe self-administration.

For more detailed guidance, consider visiting The Association of Diabetes Care & Education Specialists.

Frequently Asked Questions

Lipohypertrophy presents as a raised, firm, and rubbery lump of fatty tissue under the skin at a frequent injection site. The area may have less feeling or be numb compared to the surrounding skin [1.4.1].

To prevent bruising, avoid injecting near the belly button, rotate injection sites, and apply light pressure with gauze after the injection without rubbing the area. Some sources suggest icing the area beforehand to constrict blood vessels [1.6.1, 1.8.4].

It can be common for injections to cause small, temporary lumps or nodules [1.2.4]. However, if a lump becomes firm, large, and persistent, it may be lipohypertrophy, which is caused by not rotating injection sites enough [1.4.1].

You should use a different injection spot for every injection. Avoid using the exact same spot more than once in a row, and keep new injections at least one inch away from the previous one. For insulin pumps, sites should be changed every two to three days [1.4.1, 1.8.4].

Signs of an infection include worsening redness that spreads, severe pain, warmth at the site, swelling, drainage of pus or fluid, and systemic symptoms like a fever or feeling unwell [1.7.5].

Yes, lipohypertrophy can reduce in size or disappear if you stop injecting in that area for at least two to three months, allowing the tissue to rest and heal. In severe cases, liposuction may be considered [1.4.1, 1.4.4].

Lipoatrophy, the loss of fat tissue, was more common with older, animal-derived insulins. It is now very rare due to the use of highly purified recombinant human insulins and insulin analogs [1.5.1, 1.9.1].