Sulfonylureas and their use in clinical practice

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Abstract

Many anti-diabetic drugs with different mechanisms of action are now available for treatment of type 2 diabetes mellitus. Sulfonylureas have been extensively used for treatment of type 2 diabetes for nearly 50 years and, even in our times, are widely used for treatment of this devastating chronic illness. Here, we review some of the available data on sulfonylureas, evaluating their mechanism of action and their effects on glycemic control. We can conclude that sulfonylureas are still the most used anti-diabetic agents: maybe this is due to their lower cost, to the possibility of mono-dosing and to the presence of an association with metformin in the same tablet. However, sulfonylureas, especially the older ones, are linked to a greater prevalence of hypoglycemia, and cardiovascular risk; newer prolonged-release preparations of sulfonylureas are undoubtedly safer, mainly due to reducing hypoglycemia, and for this reason should be preferred.

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Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin.

S Bowker, S Majumdar, P Veugelers … (2006)

Numerous studies have identified an increased risk of cancer in type 2 diabetes. We explored the association between antidiabetic therapies and cancer-related mortality in patients with type 2 diabetes, postulating that agents that increase insulin levels might promote cancer. This was a population-based cohort study using administrative databases from Saskatchewan Health. Cancer-related mortality was compared among inception cohorts of metformin users and sulfonylurea monotherapy users. Multivariate Cox regression was used to estimate the hazard ratio (HR) of cancer-related mortality, after adjusting for age, sex, insulin use, and chronic disease score. All statistical tests were two-sided. We identified 10,309 new users of metformin or sulfonylureas with an average follow-up of 5.4 +/- 1.9 years (means +/- SD). The mean age for the cohort was 63.4 +/- 13.3 years, and 55% were men. Cancer mortality over follow-up was 4.9% (162 of 3,340) for sulfonylurea monotherapy users, 3.5% (245 of 6,969) for metformin users, and 5.8% (84 of 1,443) for subjects who used insulin. After multivariate adjustment, the sulfonylurea cohort had greater cancer-related mortality compared with the metformin cohort (adjusted HR 1.3 [95% CI 1.1-1.6]; P = 0.012). Insulin use was associated with an adjusted HR of cancer-related mortality of 1.9 (95% CI 1.5-2.4; P < 0.0001). Patients with type 2 diabetes exposed to sulfonylureas and exogenous insulin had a significantly increased risk of cancer-related mortality compared with patients exposed to metformin. It is uncertain whether this increased risk is related to a deleterious effect of sulfonylurea and insulin or a protective effect of metformin or due to some unmeasured effect related to both choice of therapy and cancer risk.

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α-Glucosidase inhibitors and their use in clinical practice

Giuseppe Derosa, Pamela Maffioli (2012)

Post-prandial hyperglycemia still remains a problem in the management of type 2 diabetes mellitus. Of all available anti-diabetic drugs, α-glucosidase inhibitors seem to be the most effective in reducing post-prandial hyperglycemia. We conducted a review analyzing the clinical efficacy and safety of α-glucosidase inhibitors, both alone and in combination with other anti-diabetic drugs, with respect to glycemic control, inflammation and atherosclerosis. α-Glucosidase inhibitors proved to be effective and safe both in monotherapy and as an add-on to other anti-diabetic drugs. Compared to miglitol and voglibose, acarbose seems to have some additive effects such as stabling carotid plaques, and reducing inflammation. Acarbose also proved to reverse impaired glucose tolerance to normal glucose tolerance.

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ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis.

T Miki, B Liss, K Minami … (2001)

Glucose-responsive (GR) neurons in the hypothalamus are thought to be critical in glucose homeostasis, but it is not known how they function in this context. Kir6.2 is the pore-forming subunit of K(ATP) channels in many cell types, including pancreatic beta-cells and heart. Here we show the complete absence of both functional ATP-sensitive K+ (K(ATP)) channels and glucose responsiveness in the neurons of the ventromedial hypothalamus (VMH) in Kir6.2-/- mice. Although pancreatic alpha-cells were functional in Kir6.2-/-, the mice exhibited a severe defect in glucagon secretion in response to systemic hypoglycemia. In addition, they showed a complete loss of glucagon secretion, together with reduced food intake in response to neuroglycopenia. Thus, our results demonstrate that KATP channels are important in glucose sensing in VMH GR neurons, and are essential for the maintenance of glucose homeostasis.

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Author and article information

Journal

Journal ID (nlm-ta): Arch Med Sci

Journal ID (iso-abbrev): Arch Med Sci

Journal ID (publisher-id): AMS

Title: Archives of Medical Science : AMS

Publisher: Termedia Publishing House

ISSN (Print): 1734-1922

ISSN (Electronic): 1896-9151

Publication date (Electronic): 11 August 2015

Publication date (Print): 12 August 2015

Volume: 11

Issue: 4

Pages: 840-848

Affiliations

[1 ]Department of Translational Medicine, University “Piemonte Orientale Amedeo Avogadro”, Novara, Italy

[2 ]AOU “Maggiore della Carità” Novara, Italy

[3 ]Department of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy

[4 ]Center for the Study of Endocrine-Metabolic Pathophysiology and Clinical Research, University of Pavia, Pavia, Italy

Author notes

Corresponding author: Dott. Luca Rossi MD, Department of Translational Medicine, University “Piemonte Orientale Amedeo Avogadro”, Novara, Italy. Phone: +3903213733276, Fax: +3903213733600. E-mail: luca.rossi_1981@ 123456yahoo.it

Article

Publisher ID: 25584

DOI: 10.5114/aoms.2015.53304

PMC ID: 4548036

PubMed ID: 26322096

SO-VID: e2b9b0cb-93de-4569-a34e-ac36246c920a

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 17 November 2012

Date revision received : 17 March 2013

Date accepted : 27 October 2013

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Sulfonylureas and their use in clinical practice

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Tobacco Prevention & Cessation

Most cited references 58

Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin.

α-Glucosidase inhibitors and their use in clinical practice

ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis.

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