Insulin mixing is the practice of combining two different types of insulin within a single syringe before injection. This technique is used to achieve both immediate (mealtime) and sustained (basal) blood sugar control with one injection, reducing the total number of daily needle sticks. Mixing requires precision and adherence to strict safety rules. All insulin mixing must only be performed under the explicit instruction and supervision of a qualified healthcare provider.
Understanding Insulin Categories and Action Times
Insulin products are categorized based on their distinct action profiles: how quickly they begin working (onset), when they reach their strongest effect (peak), and how long they continue to lower blood sugar (duration). The chemical formulation of each insulin type dictates these characteristics, determining safety when combining types.
Rapid-acting insulins, such as insulin aspart or lispro, have an onset of around 5 to 15 minutes, peak quickly within one to two hours, and have a short duration of action of approximately four to six hours. Short-acting or Regular insulin takes slightly longer, with an onset of 30 to 60 minutes, a peak between two and four hours, and a duration of six to eight hours. Both rapid and short-acting insulins are used to cover blood sugar spikes from meals.
Intermediate-acting insulin, specifically Neutral Protamine Hagedorn (NPH), provides a longer effect, with an onset of one to two hours, a peak between four and 12 hours, and a duration lasting 12 to 18 hours. NPH is a cloudy solution because the insulin is suspended with protamine, a protein that slows its absorption. Long-acting insulins, like glargine or detemir, are designed to provide a steady, peak-less level of insulin over 14 to 24 hours or more, acting as the basal, or background, insulin.
Standard Rules for Combining Insulins
The most common instance of manual insulin mixing involves combining Intermediate-acting (NPH) insulin with Short-acting (Regular) insulin. This combination is effective because it provides a rapid onset of action from the Regular insulin to cover an immediate meal, followed by the prolonged, intermediate-acting coverage from the NPH. The two insulins are chemically compatible in the syringe, and NPH does not significantly interfere with the Regular insulin’s immediate function.
This mixing allows a patient to administer both their mealtime and background doses in a single injection, simplifying their daily regimen. The ratio of the two insulins must be carefully maintained as prescribed by the healthcare team to ensure predictable blood sugar control. Due to the complexities of manual mixing, many patients now use commercially available pre-mixed insulins, which are manufactured with a fixed ratio of an intermediate-acting and a short or rapid-acting insulin.
Pre-mixed products, such as 70% NPH and 30% Regular, eliminate the need for patients to manually draw up two separate doses. While these options offer simplicity, they also mean less flexibility in adjusting individual insulin doses, requiring a doctor’s guidance. The timing of the injection after mixing is also important, as the mixture must be administered within a short window, typically five to 15 minutes, to prevent the Regular insulin’s effect from decreasing.
Insulin Types That Must Never Be Mixed
Modern Long-acting insulins, such as Glargine (Lantus, Basaglar) and Detemir (Levemir), must never be mixed with any other type of insulin. Mixing these long-acting insulins with a short- or rapid-acting insulin compromises the long-acting formulation and leads to unpredictable absorption. These insulins are specifically engineered to provide a steady, prolonged release by utilizing unique chemical properties.
Insulin Glargine, for example, is formulated in an acidic solution to create a micro-precipitate when injected into the neutral pH environment of the subcutaneous tissue. This precipitate slowly dissolves over a day, ensuring a peak-less, steady release of insulin.
Introducing a neutral pH insulin, like Regular or NPH, into the syringe with Glargine disrupts this acidic formulation. This chemical interference destroys the slow-release mechanism, causing the Glargine to be absorbed much faster than intended. This unpredictable action can lead to dangerous fluctuations in blood sugar control and an increased risk of severe hypoglycemia. Therefore, if a patient uses one of these long-acting insulins, it must be administered as a separate injection at a different site than any other insulin.
The Step-by-Step Mixing Procedure
When a healthcare provider instructs a patient to manually mix Regular and NPH insulin, the procedure must be followed precisely. The first step involves gently rolling the cloudy NPH vial between the palms to resuspend the insulin, preventing ingredient settling that could lead to an inaccurate dose. Shaking the vial is avoided, as this creates air bubbles that interfere with accurate dose measurement.
After preparing the NPH, air equal to the prescribed dose of NPH is injected into the NPH vial, followed by injecting air equal to the prescribed dose of Regular insulin into the Regular insulin vial. This equalizes the pressure within the vials, making it easier to withdraw the correct amount of fluid.
The most critical rule is drawing the clear (Regular) insulin into the syringe first, before drawing the cloudy (NPH) insulin. This “clear before cloudy” order prevents trace amounts of NPH from entering and contaminating the Regular insulin vial. If NPH were introduced, the protamine would alter the action profile of the Regular insulin remaining in the vial. Once the clear insulin is drawn, the syringe is inserted into the NPH vial, the correct dose is withdrawn, and the mixture must then be injected immediately.