Home > News > Basal Insulin Inadequacy versus Failure – Using Appropriate Terminology
Diabetes
Read Time: 3 mins

Basal Insulin Inadequacy versus Failure – Using Appropriate Terminology

Published Online: August 19th 2015 European Endocrinology, 2015;11(2):79–80 DOI: http://doi.org/10.17925/EE.2015.11.02.79
Authors: Sanjay Kalra, Yashdeep Gupta
Quick Links:
Abstract
Article
Article Information
Abstract:
Overview

This editorial focuses on appropriate terminology related to basal insulin therapy. The authors analyse current usage of ‘basal insulin failure’, and propose ‘basal insulin inadequacy’ as a better descriptor for persons not responding to basal insulin alone. The pharmacokinetic and pharmacodynamic differences between various basal insulin preparations are highlighted. Based upon these, a drug-specific definition for insulin inadequacy is suggested, instead of a generic class-based labelling.

Keywords

Basal insulin failure, basal insulin inadequacy, degludec, detemir, glargine, neutral protamine Hagedorn, type 2 diabetes, terminology

Article:

Basal insulin therapy is recommended as a first-line injectable therapy in persons with type 2 diabetes who do not respond to metformin monotherapy. Insulin works to control fasting glycaemia, and it is expected that metformin (with or without other drugs) will suffice apropos post-prandial euglycaemia. In many patients, however, basal insulin is unable to achieve adequate glycaemic control. This has been termed basal insulin failure. However, in the light of newer developments, we suggest a more appropriate term, basal insulin inadequacy, and discuss how it can be used.

Basal Insulin Failure

According to the current American Diabetes Association (ADA)/ European Association for Study of Diabetes (EASD) guidelines, change of basal insulin therapy is indicated if the treatment strategy fails to achieve normal glycated haemoglobin (HbA1c) in spite of adequate fasting control, or if >0.5 μ/kg/day of basal insulin is required.1 Basal insulin failure has earlier been defined as the inability to achieve a pre-decided target glycaemic control, after optimisation of lifestyle modification measures and maximal titration of basal dose beyond which unacceptable hypoglycaemia will occur.2

Basal Insulin Inadequacy

The current nomenclature implies that basal insulin has ‘failed’, while actually it may have succeeded in achieving fasting euglycaemia. Thus a more appropriate terminology is ‘basal insulin inadequacy’. This conveys a more accurate message that basal insulin is inadequate for the particular patient’s need. Inadequacy avoids the negative connotation associated with the word ‘failure’. It does not pass judgmental opinion on either the patient’s efforts to manage lifestyle or the physician’s choice of therapeutic strategy.

Basal Insulin Dissimilarity

All basal insulins are not alike. Each basal insulin and basal analogue has a unique structure, which contribute to specific pharmacokinetic and

pharmacodynamic characteristics.3 These properties allow a systematic listing of basal insulin as intermediate-, long- and ultra-long-acting molecules (see Tables 1 and 2). The differences in duration of action, glycaemic variability and risk of hypoglycaemia, specifically nocturnal hypoglycaemia, may allow for substitution of one basal insulin for another, in case adequate control is not achieved with a particular preparation. Thus, a new strategy for intensification of therapy is available for persons not responding to basal therapy: a switch to a longer-acting basal insulin.

Such a therapy is supported by mechanistic studies, randomised controlled trials (RCTs) and meta-analysis. Insulin degludec, for example, has been shown to have a longer half-life and duration of action, with significantly less glycaemic variability than glargine.4

RCTs and meta-analyses report a significantly lower incidence of hypoglycaemia and nocturnal hypoglycaemia, while achieving better fasting glucose control, in persons randomised to insulin degludec compared with glargine.5–8 Refractory patients, switched from glargine to degludec, have also been reported to achieve good glycaemic control in clinical practice.9,10 Cost-effectiveness of such a shift is also found to be beneficial.11,12 Thus, the clinical phenomenon of ‘basal insulin inadequacy’ may be drug-specific. Inability of a particular basal insulin to achieve adequate glycaemic control does not imply that all basal insulins will be inadequate for the purpose. Applied to a patient not responding to glargine, the phrase ‘basal insulin inadequacy’ may not be valid for all basal insulins.


We therefore suggest the following terminology and definitions:

  • Basal insulin inadequacy may be defined as the inability of all
    basal insulin preparations, prescribed alone or in combination
    with various oral glucose-lowering drugs, to achieve pre-decided
    glycaemic targets, without causing unacceptable hypoglycaemia
    or weight gain, in spite of optimal lifestyle modification and
    maximal dose titration.
  • Intermediate-, long-acting and ultra-long-acting insulin inadequacy
    may be used to describe persons who do not respond to maximal
    doses of NPH, glargine and detemir and degludec, respectively.
Article Information:
Disclosure

Sanjay Kalra and Yashdeep Gupta have no conflicts of interest to declare. No funding was received for the publication of this article.

Correspondence

Sanjay Kalra, Department of Endocrinology, Bharti Hospital, Karnal, India. E: brideknl@gmail.com

Open Access

This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation
and reproduction provided the original author(s) and source are given appropriate credit.

Received

2015-07-09T00:00:00

References

1. Inzucchi S, Bergenstal R, Buse J, et al., Management of hyperglycemia in type 2 diabetes, 2015: a patient centered approach update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes, Diabetes Care, 2015;38:140–9.
2. Buse JB, Bergenstal RM, Glass LC, et al., Use of twice-daily exenatide in basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial, Ann Intern Med, 2011;154:103–12.
3. Kalra S, Newer basal insulin analogues: degludec, detemir, glargine, J Pak Med Assoc 2013;63:1442–4.
4. Heise T, Hermanski L, Nosek L, et al., Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes, Diabetes Obes Metab, 2012;14:859–64.
5. Zinman B, Prillis-Tsimikar A, Cariou B, et al., Insulin degludec versus glargine in insulin naive patients with type 2 diabetes: a randomized treat to target trial (BEGIN Once Long), Diabetes Care, 2012;35:2464–71.
6. Ratner RE, Gough SCL, Mathieu C, et al., Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2 and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials, Diabetes Obes Metab, 2013;5:175–84.
7. Kalra S, Insulin degludec: a significant advancement in ultralong-acting basal insulin, Diabetes Ther, 2013;4:167–73.
8. Kalra S, Unnikrishnan AG, Baruah M, et al., Degludec insulin: a novel basal insulin, Indian J Endocrinol Metab, 2011;15(Suppl. 1):S12–6.
9. Hamasaki H, Yanai H, Switching from insulin glargine to insulin degludec reduced HbA1c, daily insulin doses and anti-insulin antibody in anti-insulin antibody-positive subjects with type 1 diabetes, Diabetes Metab, 2014;6:481–2.
10. Sinha B, Gangopadhyay KK, Ghosal S, Is insulin degludec a more effective treatment for patients using high doses of insulin glargine but not attaining euglycemia? Some case reports from India, Diabetes Metab Syndr Obes, 2014;7:225–8.
11. Evans M, Wolden M, Gundgaard J, et al., Cost-effectiveness of insulin degludec compared with insulin glargine in a basalbolus regimen in patients with type 1 diabetes mellitus in the UK, J Med Econ, 2014;18:56–68.
12. Evans M, Wolden M, Gundgaard J, et al., Cost‐effectiveness of insulin degludec compared with insulin glargine for patients with type 2 diabetes treated with basal insulin–from the UK health care cost perspective, Diabetes Obes Metab, 2014;16:366–75.

Further Resources

Share this Article
Related Content In Diabetes
  • Copied to clipboard!
    accredited arrow-downarrow_leftarrow-right-bluearrow-right-dark-bluearrow-right-greyarrow-right-orangearrow-right-whitearrow-right-bluearrow-up-orangeavatarcalendarchevron-down consultant-pathologist-nurseconsultant-pathologistcrosscrossdownloademailexclaimationfeedbackfiltergraph-arrowinterviewslinkmdt_iconmenumore_dots nurse-consultantpadlock patient-advocate-pathologistpatient-consultantpatientperson pharmacist-nurseplay_buttonplay-colour-tmcplay-colourAsset 1podcastprinter scenerysearch share single-doctor social_facebooksocial_googleplussocial_instagramsocial_linkedin_altsocial_linkedin_altsocial_pinterestlogo-twitter-glyph-32social_youtubeshape-star (1)tick-bluetick-orangetick-whiteticktimetranscriptup-arrowwebinar Department Location NEW TMM Corporate Services Icons-07NEW TMM Corporate Services Icons-08NEW TMM Corporate Services Icons-09NEW TMM Corporate Services Icons-10NEW TMM Corporate Services Icons-11NEW TMM Corporate Services Icons-12Salary £ TMM-Corp-Site-Icons-01TMM-Corp-Site-Icons-02TMM-Corp-Site-Icons-03TMM-Corp-Site-Icons-04TMM-Corp-Site-Icons-05TMM-Corp-Site-Icons-06TMM-Corp-Site-Icons-07TMM-Corp-Site-Icons-08TMM-Corp-Site-Icons-09TMM-Corp-Site-Icons-10TMM-Corp-Site-Icons-11TMM-Corp-Site-Icons-12TMM-Corp-Site-Icons-13TMM-Corp-Site-Icons-14TMM-Corp-Site-Icons-15TMM-Corp-Site-Icons-16TMM-Corp-Site-Icons-17TMM-Corp-Site-Icons-18TMM-Corp-Site-Icons-19TMM-Corp-Site-Icons-20TMM-Corp-Site-Icons-21TMM-Corp-Site-Icons-22TMM-Corp-Site-Icons-23TMM-Corp-Site-Icons-24TMM-Corp-Site-Icons-25TMM-Corp-Site-Icons-26TMM-Corp-Site-Icons-27TMM-Corp-Site-Icons-28TMM-Corp-Site-Icons-29TMM-Corp-Site-Icons-30TMM-Corp-Site-Icons-31TMM-Corp-Site-Icons-32TMM-Corp-Site-Icons-33TMM-Corp-Site-Icons-34TMM-Corp-Site-Icons-35TMM-Corp-Site-Icons-36TMM-Corp-Site-Icons-37TMM-Corp-Site-Icons-38TMM-Corp-Site-Icons-39TMM-Corp-Site-Icons-40TMM-Corp-Site-Icons-41TMM-Corp-Site-Icons-42TMM-Corp-Site-Icons-43TMM-Corp-Site-Icons-44TMM-Corp-Site-Icons-45TMM-Corp-Site-Icons-46TMM-Corp-Site-Icons-47TMM-Corp-Site-Icons-48TMM-Corp-Site-Icons-49TMM-Corp-Site-Icons-50TMM-Corp-Site-Icons-51TMM-Corp-Site-Icons-52TMM-Corp-Site-Icons-53TMM-Corp-Site-Icons-54TMM-Corp-Site-Icons-55TMM-Corp-Site-Icons-56TMM-Corp-Site-Icons-57TMM-Corp-Site-Icons-58TMM-Corp-Site-Icons-59TMM-Corp-Site-Icons-60TMM-Corp-Site-Icons-61TMM-Corp-Site-Icons-62TMM-Corp-Site-Icons-63TMM-Corp-Site-Icons-64TMM-Corp-Site-Icons-65TMM-Corp-Site-Icons-66TMM-Corp-Site-Icons-67TMM-Corp-Site-Icons-68TMM-Corp-Site-Icons-69TMM-Corp-Site-Icons-70TMM-Corp-Site-Icons-71TMM-Corp-Site-Icons-72