Can I use NPH (Neutral Protamine Hagedorn) insulin with lispro insulin?

From the Guidelines

Yes, you can use NPH (Neutral Protamine Hagedorn) insulin together with lispro insulin as part of a diabetes management regimen. This combination is actually quite common and provides complementary coverage throughout the day. NPH is an intermediate-acting insulin that typically peaks 4-10 hours after injection and lasts about 10-16 hours, while lispro (brand name Humalog) is a rapid-acting insulin that starts working within 15 minutes, peaks in about 1 hour, and lasts 2-4 hours. When using both, you would typically take lispro before meals to cover the immediate rise in blood glucose from eating, while NPH provides background insulin coverage between meals and overnight. These insulins can be injected separately or, in some cases, mixed in the same syringe just before injection. However, premixing should only be done immediately before injection and not stored. It's essential to follow your healthcare provider's specific instructions regarding dosing, timing, and injection sites, as outlined in the most recent guidelines, such as those from the American Diabetes Association 1. The combination works well because it mimics the body's natural insulin pattern more closely than either insulin type alone, with lispro handling quick glucose rises after meals and NPH providing more sustained coverage. Key considerations for this regimen include:

• Starting with a basal insulin dose and adjusting as needed based on blood glucose levels and individual patient needs 1
• Adding prandial insulin, such as lispro, before meals to control postprandial glucose spikes 1
• Monitoring blood glucose levels regularly to adjust insulin doses and prevent hypoglycemia or hyperglycemia 1
• Considering the use of fixed-ratio combination products, such as IDegLira or iGlarLixi, for convenience and improved glycemic control 1

From the Research

Insulin Regimens

• The use of NPH (Neutral Protamine Hagedorn) insulin with lispro insulin has been studied in various clinical trials 2, 3, 4, 5, 6.
• These studies have investigated the efficacy and safety of combining NPH insulin with lispro insulin in patients with type 1 and type 2 diabetes.

Efficacy of Combination Therapy

• A study published in 1997 found that treatment with insulin lispro in combination with NPH human insulin resulted in lower postprandial glucose levels and smaller increases in glucose level after meals compared with treatment with regular human insulin 2.
• Another study published in 1998 found that reduced-dose lunchtime lispro plus NPH maintained the improvement in postprandial blood glucose control with no deterioration in interprandial blood glucose control 3.
• A multicenter randomized crossover trial published in 2001 found that preprandial combination of lispro and NPH insulin improved overall blood glucose control in type 1 diabetic patients 4.

Comparison of Insulin Regimens

• A study published in 2007 compared a prandial regimen (premeal insulin lispro + bedtime NPH) with a basal regimen (twice-daily NPH) in patients with type 2 diabetes, and found that the prandial regimen reduced hemoglobin A1c (HbA1c) without increasing hypoglycemia or insulin dose 5.
• Another study published in 2003 compared lunch and bedtime NPH insulin plus mealtime insulin Lispro therapy with premeal regular insulin plus bedtime NPH insulin therapy in type 2 diabetes, and found that the Lispro group had significantly lower HbA1c values and postprandial glucose values 6.

Safety and Tolerability

• The studies found that the combination of NPH insulin with lispro insulin was generally well-tolerated, with similar rates of hypoglycemia and weight gain compared with other insulin regimens 2, 3, 4, 5, 6.