CARDIOVASCULAR JOURNAL OF AFRICA • Volume 25, No 2, March/April 2014
AFRICA
83
Review Article
Optimal utilisation of sulphonylureas in resource-
constrained settings
Poobalan Naidoo, Virendra Rambiritch, Neil Butkow, Selvarajah Saman
Abstract
Sulphonylureas (SUs) are oral anti-diabetic drugs (OADs)
that were introduced more than 60 years ago. Clinicians are
familiar with their use and they remain extensively used.
However, the SU class is associated with adverse effects of
weight gain and hypoglycaemia. In addition, their effects on
cardiovascular events remain contentious. Newer classes of
anti-diabetic agents have been developed and these agents
are weight neutral (di-peptidyl peptidase IV inhibitors), while
others reduce weight (glucagon-like peptide analogues and
sodium glucose co-transporter inhibitors). Furthermore, the
newer agents are less likely to cause hypoglycaemia and have
a potentially better cardiovascular safety profile. However, the
newer agents are more costly than SUs and their long-term
safety is unknown. It is therefore likely that SUs will continue
to be used, and more so in resource-limited settings. One may
mitigate the adverse effects of weight gain and hypoglycaemia
associated with the SU class by using members within this
class that are less probable to cause these adverse effects.
Furthermore, the specific SU must be used at the lowest effec-
tive therapeutic dose. In patients at high risk of SU-induced
hypoglycaemic episodes (frail, clinically significant renal
impairment), or patients in whom hypoglycaemic episodes
may have devastating effects (bus drivers), newer anti-diabetic
agents may be a justifiable alternative option.
Keywords:
type 2 diabetes mellitus, sulphonylureas, resource-
constrained settings
Submitted 27/11/13, accepted 4/2/14
Cardiovasc J Afr
2014;
25
: 83–85
DOI: 10.5830/CVJA-2014-007
Sulphonylureas (SUs) were developed in the 1950s.
1
They reduce
blood glucose levels by increasing insulin secretion from the
pancreatic beta-cells. At the cellular level SUs block potasssium
(K
ATP
) channels and increase calcium influx, which results in the
release of insulin from the vesicles.
1
Currently there is an expansion in the therapeutic
armamentarium of agents for type 2 diabetes. The therapeutic
landscape is complex and comprises pharmacologically distinct
molecules, including biguanides, sulphonylureas, incretin-based
therapies and renal sodium glucose co-transporter (SGLT)
inhibitors.
2
As novel therapies are inevitably associated with
increased costs, this article focuses on ways to utilise SUs in
a manner that maximises efficacy and concurrently minimises
adverse effects.
Efficacy and durability of glycaemic effect
Type 2 diabetes patients benefit from intensive multifactorial risk-
factor modification.
3
In addition to control of blood glucose and
glycosylated haemoglobin (HbA
1c
) levels, lifestyle modification
(diet and exercise), and control of blood pressure and cholesterol
levels are crucial to reduce the risk of cardiovascular disease in
type 2 diabetes patients.
3
For blood glucose control, HbA
1c
level is the most robust
endpoint used in clinical trials to evaluate the efficacy of anti-
diabetic drugs. HbA
1c
is an indicator of three-month average blood
glucose levels. Reduction in HbA
1c
levels reduces microvascular
complications.
4-6
SUs reduce HbA
1c
levels by approximately 1.5%,
2
but their
effect on cardiovascular outcomes is contentious. Their HbA
1c
level-reducing ability is adequate but durability is limited.
7
Limited durability is probably secondary to type 2 diabetes
mellitus being a progressive disease characterised by gradual
reduction in beta-cell mass and function. If there are limited
numbers of beta-cells, then the action of this class is limited
because the mode of action necessitates the presence of beta-
cells; they cannot increase insulin secretion if there are no beta-
cells present to synthesise and release insulin.
Furthermore, secondary failure has also been attributed to
the detrimental effects of SUs on residual pancreatic beta-cells.
8
Secondary failure rates were found to be lowest with gliclazide
Boehringer Ingelheim, Johannesburg, South Africa
Poobalan Naidoo, BPharm, MB BCh, MMedSc (Pharmacol), FCP,
University of Kwa-Zulu Natal, Durban, South Africa
Virendra Rambiritch, PhD
Department of Pharmacy and Pharmacology, Faculty
of Health Sciences, University of Witwatersrand,
Johannesburg, South Africa
Neil Butkow, PhD
Port Shepstone Regional Hospital and University of
Kwa-Zulu Natal, Durban, South Africa
Selvarajah Saman, MB BCh, MD, MRCP (UK), FRCP (UK)
