A Comprehensive Clinical and Pharmacological Review of Isophane (NPH) Insulin

Introduction and Drug Profile

Overview and Therapeutic Class

Isophane insulin, more commonly known by the synonym NPH (Neutral Protamine Hagedorn) insulin, is a cornerstone medication in the management of diabetes mellitus. It is classified as an intermediate-acting human insulin preparation within the broader therapeutic class of antidiabetic agents.[1] Its primary function is to provide basal (background) glycemic control by regulating glucose metabolism over an extended period. The clinical indications for isophane insulin are broad, encompassing the management of Type 1 Diabetes, Type 2 Diabetes, and Gestational Diabetes, which underscores its extensive utility across the spectrum of diabetic conditions.[3]

The nomenclature of NPH insulin serves as a concise summary of its innovative formulation. The term "Neutral Protamine Hagedorn" refers to the three key characteristics that defined its development: a suspension with a neutral pH (pH=7), the inclusion of the protein protamine to delay absorption, and its invention by the Danish researcher Hans Christian Hagedorn in 1946.[4] This formulation represented a significant advancement in diabetes care, providing a more sustained insulin effect compared to the short-acting preparations available at the time.

Historical Context and Formulation

The development of isophane insulin is a landmark achievement in the history of engineered drug delivery. Following the creation of protamine insulin in 1936, which first introduced the concept of using a protein to prolong insulin's action, NPH insulin was introduced in 1946 as a refined and more predictable formulation.[4] Its creation addressed the critical clinical need for an insulin that could provide coverage between meals and overnight, reducing the number of daily injections required for patients.