Mixing two different types of insulin into a single syringe injection is a common practice in diabetes management. This technique reduces the total number of daily injections while still providing comprehensive blood sugar control. Combining a fast-acting insulin for mealtime coverage with a longer-acting insulin for basal needs simplifies the daily routine. Achieving this balance requires precise knowledge of which insulins can be safely combined and the correct technique to ensure medication effectiveness.
Compatible Insulin Types for Mixing
The ability to mix insulins centers around the intermediate-acting insulin known as Neutral Protamine Hagedorn (NPH), which appears cloudy in its vial. NPH is formulated at a neutral pH, allowing it to be safely combined with other neutral insulins without causing immediate chemical changes. The two main compatible groups are Short-acting and Rapid-acting insulins.
Short-acting insulin, often called Regular insulin (e.g., Humulin R, Novolin R), is a clear solution that provides quick, pre-meal coverage. When mixed with NPH, the combination delivers both a fast-acting component and a prolonged basal component in one shot. Rapid-acting insulins, such as insulin lispro (Humalog) and insulin aspart (Novolog), can also be mixed with NPH.
Mixing these types allows the rapid insulin to handle the post-meal glucose spike, while the NPH component provides sustained coverage. When combining a rapid-acting insulin with NPH, the mixture must be injected immediately after it is drawn into the syringe. This practice prevents the NPH from binding to the rapid-acting insulin and delaying its onset of action.
Insulins That Must Never Be Combined
Certain insulin types must never be mixed with any other insulin in the same syringe. This restriction applies mainly to Long-acting and Ultra-long-acting basal insulins, such as insulin glargine (Lantus, Basaglar, Toujeo) and insulin detemir (Levemir). These insulins are designed with specific pH levels or stabilizing additives that create their long duration of action.
Insulin glargine is highly acidic; mixing it with a neutral-pH insulin like NPH or Regular insulin immediately alters its chemical structure. This change causes the glargine to precipitate, destroying its intended slow-release profile and rendering the entire dose ineffective and unpredictable. Similarly, insulin degludec (Tresiba), an ultra-long-acting product, should not be diluted or mixed.
Using a syringe contaminated with these incompatible insulins can lead to a significant loss of efficacy for the long-acting component, resulting in erratic blood sugar control. The primary safety risk is the loss of the long-acting insulin’s predictable release, which can lead to severe hyperglycemia or unpredicted hypoglycemia. Furthermore, pre-mixed insulin formulations, which are already fixed combinations, should also not be mixed with additional insulin.
Step-by-Step Guide for Drawing Up Mixed Insulin
The process for drawing up two compatible insulins, such as Regular and NPH, must follow a precise sequence known as “Clear before Cloudy” to maintain the purity of the vials. Before starting, the cloudy NPH vial must be gently rolled between the palms to ensure the suspension is evenly mixed; shaking can create bubbles that interfere with accurate dosing. The first step involves drawing air into the syringe equal to the total dose of the cloudy (NPH) insulin.
Clear Before Cloudy Steps
- Inject this air into the NPH vial, but remove the needle without drawing any insulin.
- Draw air equal to the dose of the clear (Regular or Rapid-acting) insulin into the syringe and inject it into the clear insulin vial.
- Draw up the required dose of the clear insulin first, preventing NPH residue from contaminating the clear insulin vial.
- Insert the needle into the cloudy NPH vial, and draw the correct dose into the syringe, which already contains the clear insulin.
- Once the full combined dose is in the syringe, the injection should be administered immediately.
This mixing procedure is only for insulin supplied in vials, as insulin pens are designed for single-use and do not permit the mixing of different formulations.
How Mixing Affects Insulin Action Profile
Combining an intermediate-acting insulin like NPH with a short- or rapid-acting insulin creates a dual-action profile. The rapid component provides a quick, strong peak to cover the immediate glucose rise following a meal. The NPH component, a crystalline suspension with protamine, dissolves slowly, providing a sustained release for background glucose control.
When a rapid-acting insulin, such as insulin lispro, is mixed with NPH, the onset and peak action of the rapid component remain largely unaffected. However, when Regular insulin is mixed with NPH, the zinc and protamine in the NPH suspension can cause some Regular insulin to bind, delaying its onset and peak time. This pharmacological change means that the timing of the injection relative to the meal must be carefully managed to prevent early high blood sugar.
The overall effect of mixing is a prolonged action from the fast-acting insulin, combined with the extended duration of the NPH, creating a single injection with both prandial and basal effects. This combined action profile provides a practical solution for patients who need both types of coverage but wish to limit their number of daily injections. Careful blood sugar monitoring is necessary to ensure effective glucose management because the combined action can vary based on the specific mixture.