Page 93 - 51 the significance--29.2_opt

SGLT-2 inhibitors

In the kidneys, two transporter proteins, sodium-glucose co-transport-
er-1 (SGLT-1) and SGLT-2 are crucial in regulating the reuptake of so-
dium and glucose back into ultra-filtrated blood. Inhibiting SGLT-2 has
72
been identified as a way of reducing glucose re-uptake and therefore
reducing blood glucose levels.
72
No compounds in this class are currently available on the market. Dapa-
gliflozin has filed for approval, while canagliflozin/empagliflozin are in
Phase 3 development. Initial SGLT-2 inhibitor data shows there are no
excessive losses of fluid, sodium, or potassium; very low risk of hypo-
glycaemia; significant reductions in HbA (~0.7%) modest weight loss
1c
(1 to 4 kg) and a lowering of systolic blood pressure (1 to 4 mmHg). 72-
75 Potential drawbacks of SGLT-2 inhibition include a slight increase
in urine volume and a tendency to increase urinary tract infections
and genital mycosis. The latter drawback is thought to be due to the
increased levels of glucose in the urine, which supports the growth of
yeasts, etc. Table 5 presents a ‘SWOT’ analysis of the SGLT-2 inhibitors.
72

Table 5. SGLT-2 inhibitors – Strengths, Weaknesses, Opportunities and Threats.

Strengths Weaknesses

z Novel mode of action z Not yet supported by a large body of late phase
clinical data
z Orally active
z Insulin-independent mode of action z Increase in urine volume
Increase in urinary tract/genital infections
z Associated with modest weight loss z No data on long-term inhibition of SGLT-2
z Associated with a low incidence of hypoglycaemia z SGLT-2 inhibition is an unknown quantity in T2DM
z Lower systolic blood pressure z management
z High selectivity – SGLT-2 not found in other tissues High selectivity – effects on other important disease
z
management parameters may be limited
Opportunities Threats
z T2DM management is moving beyond simple z New compounds with novel modes of action
glycaemic parameters emerging
z The position of many OADs is being eroded by z Long term consequences of higher glucose levels
safety concerns (e.g. SUs, TZDs) in the urine
z Patient-centric treatment is increasingly important

93