Can regular (short‑acting) insulin be used together with NPH insulin?

Can Short-Acting Insulin Be Mixed with NPH?

Yes, short-acting (regular) insulin can be safely mixed with NPH insulin in the same syringe and used immediately or stored for future use. 1

Key Mixing Guidelines

NPH and Short-Acting Insulin Compatibility

• NPH and short-acting insulin formulations when mixed may be used immediately or stored for future use, providing flexibility in treatment administration 1
• The American Diabetes Association explicitly endorses this combination, stating that currently available NPH and short-acting insulin formulations are compatible for mixing 1
• When mixing these insulins, there is only a slight decrease in absorption rate but no reduction in total bioavailability, meaning the overall glucose-lowering effect remains intact 1

Clinical Application in Practice

• The 2025 American Diabetes Association Standards recommend self-mixed/split insulin plans combining NPH with short-acting insulin as a viable intensification strategy when A1C is above goal 1
• A typical regimen involves giving 2/3 of the total daily dose before breakfast and 1/3 before dinner, with short-acting insulin added to each NPH injection 1
• When adding prandial insulin to NPH, initiation of a self-mixed or premixed insulin plan decreases the number of injections required, improving adherence 1

Timing Considerations

• Mixed NPH and short-acting insulin should be administered according to the short-acting insulin's timing requirements (typically 30-45 minutes before meals) 1
• Patients already well-controlled on a particular mixed-insulin regimen should maintain their standard procedure for preparing insulin doses 1

Critical Pitfalls to Avoid

What NOT to Mix with NPH

• Do NOT mix NPH with lente insulins - phosphate-buffered insulins like NPH should never be mixed with lente insulins because zinc phosphate precipitation occurs, unpredictably converting longer-acting insulin to short-acting insulin 1, 2, 3
• Do NOT mix insulin glargine with any other insulin due to its low pH diluent, which causes incompatibility 1, 4

Lente Insulin Warnings

• Mixing short-acting and lente insulins is NOT recommended except for patients already adequately controlled on such a mixture 1
• Zinc ions in lente insulins bind with short-acting insulin and delay onset of action unpredictably, with binding equilibrium potentially taking up to 24 hours 1, 2, 3

Rapid-Acting Insulin Analogs with NPH

• Rapid-acting insulin analogs (lispro, aspart) can also be mixed with NPH without significant blunting of the rapid-acting insulin's onset 1, 2, 3
• When rapid-acting insulin is mixed with NPH, the mixture should be injected within 15 minutes before a meal 1, 3
• Clinical trials demonstrate that postprandial blood glucose response remains similar whether rapid-acting insulin is mixed with NPH or used separately 1, 3

Commercially Available Premixed Options

• Premixed formulations are available (70% NPH/30% regular, 50% NPH/50% regular) and may be used if the insulin ratio matches patient requirements 1, 2
• These eliminate the need for patients to mix insulins themselves while maintaining the benefits of combination therapy 1