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Classification of non-insulin glucose lowering drugs.

Byline: Sanjay Kalra


This article proposes a simple and pragmatic classification of non-insulin glucose lowering drugs, which makes the pharmacology of diabetes easy to understand. While it is based on predominant mechanism of action, it encourages a pathophysiology-based approach to choice of drugs and drug combinations/permutations.

Keywords: Alpha-glucosidase inhibitors, DPP4 inhibitors, GLP1 receptor agonists, Metformin, Pioglitazone, Pramlintide, SGLT2 inhibitors.


The number of glucose-lowering drug classes has increased markedly over the past two decades.1 The list includes 'traditional' drugs such as sulfonylureas and metformin, 'newer' drugs like dipeptidyl peptidase-4 inhibitors (DPP4I) and sodium glucose co-transporter-2 inhibitors (SGLT2I), and injectables, e.g., glucagon-like peptide-1 receptor agonists (GLP1RA) and pramlintide.

Each class of drugs contains varying number of molecules, with distinct pharmacokinetic and pharmaco dynamic properties, which lay claim to their 'unique' status. The situation is further magnified by multiple mechanisms of action, and pleiotropic effects identified for each drug.2

Taxonomic Model

This poses a pedagogic challenge for teachers, practitioners and students of diabetology, who find it difficult to assimilate the large body of pharmacological information, and translate it into clinical use. We propose a pragmatic taxonomic model for systematic classification of all non-insulin glucose-lowering drugs, to help simplify understanding of these medications, and promote their rational use. This classification follows a cladistic approach, classifying drugs into groups called clades3 with a common underlying patho-physiologic principle. Each clade includes different classes of drugs.

All glucose- lowering drugs (except insulin) listed in the American Diabetes Association Standards of Care 2016 and the American Association of Clinical Endocrinologists 2016 algorithm are included in this classification.1,4 Insulin has been excluded as its classification merits focused discussion.5 If, required, however, the proposed taxonomic system can be expanded to list insulin along with secretagogues.


This classification is based upon mechanism of action, and hence, can be called pharmacological in nature. At the same time, however, it provides a basis for rational use of non-insulin drugs. This highlights the clinical nature of this classification. To a large extent, this systematic division delineates, and supports, scientific use of combination therapy, by encouraging prescribers to craft synergistic combinations based upon mode of action.6

Most drugs have multiple mechanisms of action: in such cases, the primary mode of action is used to place the drug class in its appropriate taxonomic slot.7,8 While no systematic study can be perfect, a classification must be easy to understand, and easy to use. It must simplify, rather than complicate, the body of knowledge it covers. It should present facts in an accurate manner, and be considered user-friendly at the same time. Such a taxonomy of glucose-lowering drugs should benefit the science of diabetology. We hope the self-explanatory classification, presented in Figure, achieves this goal.


1. Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, Dagogo-Jack S, DeFronzo RA, Einhorn D, Fonseca VA, Garber JR. Consensus statement by the American association of clinical endocrinologists and American college of endocrinology on the comprehensive type 2 diabetes management algorithm-2016 executive summary. Endocrine Practice. 2016; 22: 84-113.

2. Kalra S, Jacob JJ, Gupta Y. Newer antidiabetic drugs and calorie restriction mimicry. Indian J Endocrinol Metabol. 2016; 20: 142.

3. Kluge AG, Wolf AJ. Cladistics: what's in a word? Cladistics. 1993; 9: 183-99.

4. American Diabetes Association. Standards of Medical Care in Diabetes-2016 Abridged for Primary Care Providers. Clinical diabetes: a publication of the American Diabetes Association. 2016; 34: 3.

5. Kalra S, Gupta Y. Number-Based Approach to Insulin Taxonomy. Diabetes Therapy. 2015; 6: 469-79.

6. Kalra S, Sahay BK, Rao MS. Fixed dose combinations in diabetes: Indian innovation, Indian pride. Indian J Endocrinol Metabol. 2012; 16: 4.

7. Shaefer Jr CF, Kushner P, Aguilar R. User's guide to mechanism of action and clinical use of GLP-1 receptor agonists. Postgrad Med. 2015; 127: 818-26.

8. Zema MJ. Colesevelam hydrochloride: evidence for its use in the treatment of hypercholesterolemia and type 2 diabetes mellitus with insights into mechanism of action. Core evidence. 2012; 7:61.

9. Mulvihill EE, Drucker DJ. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocrine Rev. 2014; 35: 992-1019.
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Publication:Journal of Pakistan Medical Association
Date:Nov 30, 2016
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