Introduction

The term “taxonomy” is used to describe the classification of various things, so the term “drug taxonomy” refers to the science of listing and describing drugs, according to various properties, in a manner which allows easy comprehension and understanding of their usage.

Traditionally, only pharmaceutical properties (e.g., chemical structure and pharmacodynamic and pharmacokinetic characteristics) have been used to separate drugs into various groups. Increasingly, however, the end user (i.e., the patient’s or community’s perspective) is considered when studying pharmacology [1, 2]. In the present work, we provide a balanced, syncretic approach to insulin taxonomy, using both patient-centered and pharmacokinetic aspects, to craft a number-based classification of insulin regimes.

This article is based on previously conducted studies and does not involve any new studies of human or animal subjects performed by any of the authors.

Current Insulin Taxonomy

Endocrinology and diabetology textbooks provide comprehensive coverage of various insulin preparations and then utilize these to discuss different insulin regimes. The current American Diabetes Association (ADA)/European Association for Study of Diabetes (EASD) 2015 guidelines use the terms “basal,” “basal plus,” “premixed,” “split-mix,” and “intensive” to describe insulin regimes [3]. Other terms used for regimes involving 3 or more injections per day are “multiple” and “intensified” insulin therapy. This drug-centered or pharmaceutical-based terminology served diabetology practitioners adequately in the past; the corresponding taxonomic methodology was able to incorporate the limited insulin preparations available, which included both traditional and modern insulins. This pharmaceutical classification of insulin regimes is not, however, syntaxic with the current emphasis on a patient-centered approach. It must be reemphasized here that it is patient-centeredness which forms the basis for recent advances in drug development and improvements in treatment guidelines.

Patient-Centered Insulin Taxonomy

Most patients of diabetes do not appreciate the pharmacodynamic or kinetic nuances of insulin preparations. What is more relevant to the person requiring insulin is the number of injections to be taken per day, the timing of administration, and the flexibility with which these timings can be adjusted. Based upon these factors, it is important to craft a fresh synopsis of insulin regimes, using the number of injections per day as the framework for systematic study. At the same time, such a classification system must address the nature of insulin preparations, whether basal, premixed, or prandial.

Modern clinical trials are available which support the use of premixed insulin in once-daily and thrice-daily dosages, as opposed to the traditional twice-daily regime. The basal insulins detemir and glargine often need to be prescribed twice daily in order to achieve adequate glycemic control. Innovative regimes utilizing combinations of rapid-acting and premixed/coformulated insulins with varying frequencies of administration have also been documented. These factors also provide important reasons to revisit current classifications of insulin preparations.

Number-Based Classification of Insulin Regimes

While a number-based terminology has already been proposed [4], it is inadequate to cover the current range of insulin preparations and the large number of regimens that they are used in. With the newer insulin analogues available, a modern, number-based classification is required. Table 1 lists the various insulin regimes and preparations as well as the frequency and timing of administration for each. All regimes enumerated in this table are backed by randomized controlled trials, as shown in Table 2.

Table 1 Insulin preparations that are currently on the market, along with the prescription patterns for them
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Table 2 Prescription patterns of currently available insulin preparations, supported by evidence from various published clinical studies
Full size table

Newer ultralong-acting basal insulins and coformulations of ultralong-acting insulin analogues with either rapid-acting insulin analogues, or with GLP-1RA (glucagon-like peptide-1 receptor agonists), have recently been introduced. While these newer preparations are a combination of two preparations, they definitely do not fit into the earlier category of premixed insulins. They differ from previous molecules in their kinetic properties as well as their versatility. Other molecules, such as PEGylated lispro, are also in advanced stages of development, and will soon be available for clinical use.

Once-daily injections include all basal, premixed, and coformulation insulins. If necessary, these can be used in a twice-daily regime. Basal insulins were initially thought to be used once a day. As NPH, glargine, and detemir do not provide adequate 24 h coverage, they may need to be used twice daily in certain patients, especially those with type 1 diabetes. The novel ultralong-acting insulin degludec provides adequate 24-h glycemic control and can be used once daily at any time of the day. These factors need to be reflected in an updated taxonomic profile of insulin.

While basal insulins are able to achieve adequate fasting control in many cases, they are unable to provide prandial coverage. Initiation of a once-daily premix or coformulation with the major meal or meal with highest glycemic excursion allows control of postprandial glucose after one meal as well. The frequency of administration of these insulin preparations can, if required, be intensified to twice or thrice daily. While biphasic human insulin or premixed analogue insulin need to be administered at antipodal meals (i.e., meals spaced roughly 12 h apart), IDegAsp (insulin degludec aspart) may be administered at two consecutive meals, provided an 8-h gap is maintained. All of these patterns of use find a place in a number-based umbrella of insulin taxonomy, as opposed to the traditional regime classification, which proposes only twice daily use of premixed insulin.

If the twice-daily regime does not achieve 24-h euglycemia, intensive insulin therapy (defined as that including 3 or more than 3 injections per day) may be required in the form of either three premix insulin injections or a basal bolus regimen. Various regimes are available in this group. Depending upon the needs of the patient, one can prescribe prandial insulin thrice a day; premixed twice and prandial once; or prandial twice and premixed/coformulation once. Basal–bolus regimes involving 3 bolus doses and 1 or 2 basal doses can also be used in refractory patients and in type 1 diabetes.

Conclusion

The number-based taxonomy is able to include all of these regimes as subclasses (Table 1), based upon published randomized controlled trials (Table 2). This arrangement makes it much simpler for the student to understand the subject of insulin pharmacotherapeutics. It helps the practitioner to appreciate the versatility of insulin and the many ways in which this life-saving molecule can be used. This system also allows the physician to choose the appropriate regime for a particular patient while following person-centeredness in letter and spirit. At the same time, choice of regime should take biomedical factors such as severity of hyperglycemia, risk of hypoglycemia, and diabesity indices into account.

Such a codification would promote appropriate choice of therapy based upon the individual’s glucophenotype, motivation level, and psychosocial limitations, ease of use, and acceptance of insulin, by sensitizing the diabetes care professional to the patient’s needs. It also facilitates the gradual intensification of therapy with the same insulin.

We therefore propose that future guidelines and recommendations utilize this person-centered arrangement of insulin regimes, rather than straitjacketing preparations according to traditional criteria.