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VOLUME 11 NUMBER 4 • NOVEMBER 2014
145
SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
Sodium-glucose co-transporter (SGLT) inhibitors:
a novel class of oral anti-diabetic drugs
P Naidoo, K Ho, V Rambiritch, N Butkow
Correspondence to: Dr P Naidoo
Medical Affairs, Boehringer Ingelheim, South Africa
poobalan.naidoo@boehringer-ingelheim.comDr K Ho
Medical Affairs, Boehringer Ingelheim, South Africa
Dr V Rambiritch
University of Kwa-Zulu Natal, Durban
Dr N Butkow
Department of Pharmacology, University of the Witwatersrand, Johannesburg
S Afr J Diabetes Vasc Dis
2014;
11
: 145–150
Abstract
Theprevalenceof type2diabetesmellitushas reachedpandemic
proportions. The armamentariumof anti-diabetic agents is vast,
but there remain unmetmedical needs. The latest addition is the
sodium glucose co-transporter inhibitors. Members of the class
include dapagliflozin, canagliflozin, empagliflozin, ipragliflozin
and tofoglilozin. This class of agents reduce blood glucose
concentrations by inhibiting renal re-absorption of glucose.
This mechanism of action is independent of beta-cell function
and insulin resistance. This article explores potential effects of
this class of agents, extrapolated from themechanismof action,
and compares these potential effects to effects demonstrated
in clinical studies.
Type 2 diabetes mellitus (T2DM) is a progressive disorder of protein,
fat and carbohydrate metabolism characterised by hyperglycaemia
and changes in the secretion of both insulin (and/or resistance to
the effects of insulin) and glucagon.
1-4
The prevalence of T2DM has reached pandemic proportions.
5
Currently, over 366 million people are living with T2DM. By 2030
this figure will have risen to approximately 552 million.
6
The global
prevalence of
T2DM
is 4.3%, with 81.2% undiagnosed.
6
Sedentary
lifestyle and high caloric intake is strongly associated with obesity,
which contributes to the T2DM pandemic.
4
Ten per cent of adults in the USA, Switzerland and Austria are
affected by T2DM. It is predicted that in the Middle East, sub-
Saharan Africa and Latin America, the prevalence will increase 2.5
times by 2030. In the economically advanced countries the increase
will be about 50% in 2030.
5
The prevalence of T2DM is increasing rapidly in sub-Saharan
Africa
7
and population prevalence rates vary from a low of 1%
in rural Uganda to 12% in urban Kenya.
8
In South Africa, the
prevalence is 7%, accounting for approximately two million cases,
with another 1.5 million remaining undiagnosed.
6
Type 2 diabetes therapy
Lifestyle modification encompassing both a carbohydrate- and fat-
restricted diet and an exercise programme remains the cornerstone
of management.
9
However, successful lifestyle modification is
challenging for the majority of patients. Furthermore, T2DM is
associated with a gradual decline in pancreatic beta-cell function
and consequently these patients eventually require medication, in
addition to lifestyle modification.
Loweringbloodglucose concentrations unequivocally reduces the
risk of microvascular complications such as nephropathy, neuropathy
and retinopathy.
10
There is inadequate evidence to show that
glycaemic control reduces macrovascular complications. However,
macrovascular complications account for a large proportion of the
morbidity and mortality in patients with T2DM and has led to many
guidelines accepting the diagnosis of T2DM as a ‘cardiovascular
risk equivalent’. Therapy for T2DM patients must therefore not only
Table 1.
Pharmacological agents for type 2 diabetes mellitus
1,13
Class
Example
Abbreviated mode
of action
Biguanides
Metformin
Decreases insulin
resistance, decreases
hepatic gluconeogenesis
Sulphonylurea
Glibenclamide,
gliclazide, glipizide,
glimepiride
Increases insulin release
from pancreas
Meglitinides
Repaglinide, nateglinide Increases insulin release
from pancreas
Thiazolidinediones
Pioglitazone
Increases insulin
sensitivity
Glucagon-like peptide-1
(GLP) analogues
Exenatide, liraglutide Incretin mimetic
Dipeptidyl peptidase IV
(DPPIV) inhibitors
Sitagliptin, vildagliptin,
saxagliptin
Reduces incretin
breakdown, thereby
increasing incretin effect
α
-Glucosidase inhibitors Acarbose
Reduces glucose
absorption from the
gastrointestinal tract
Insulin
Ultra short-acting insulin
analogues
Aspart
Lispro
Glulisine
Short-acting insulin
analogues
‘Regular’ human
insulin
Intermediate-acting
insulin
Neutral protamine
Hagedorn (NPH)
Long-acting insulin
analogues
Glargine
Detemir
Facilitates glucose transit
from blood to tissues.
Inhibits glycogenolysis
and hepatic
gluconeogenesis