11/13/24, 7\:44 PM Guide | Prescribing sodium-glucose co-transporter 2 (SGLT2) inhibitors

Prescribing sodium-glucose co-transporter 2 (SGLT2) inhibitors

Table of contents

Introduction

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a group of medicines which reversibly inhibit SGLT2 in the renal
proximal convoluted tubule and are commonly also known as ‘Flozins’
1
.
In this article, we will cover the medicines in this group (canagli
discuss their use in clinical practice, including key monitoring, side e

Indications

Type 2 diabetes

SGLT2 inhibitors were initially licensed for the management of type 2 diabetes either as monotherapy in those patients who
cannot tolerate metformin or for whom diet and exercise alone do not provide adequate glycaemic control; or in combination
with other medication.
1,2
If a patient has chronic heart failure or established atherosclerotic cardiovascular disease with type 2 diabetes, it is
recommended to o
tolerability is established.
For adults with chronic kidney disease (CKD) and type 2 diabetes already on an angiotensin converting enzyme (ACE) inhibitor
or angiotensin receptor blocker (ARB), an SGLT2 inhibitor can be o
2

Chronic heart failure

Dapaglichronic heart failure. NICE
recommends they can be used for those with reduced ejection fraction as an add-on to optimised standard care, including an
ACE inhibitor and beta-blocker under a cardiologist or specialist in heart failure.
This is irrespective of any diagnosis of diabetes.
3,4

Chronic kidney disease

Dapaglichronic kidney disease (irrespective of any diagnosis of
diabetes), as it has been shown to slow the progression of CKD.

Mode of action

SGLT2 inhibitors work by inhibiting the SGLT2 transporter protein in the renal proximal convoluted tubule, which reduces
reabsorption of renally
The urinary excretion of glucose also creates osmotic diuresis producing a reduction in systolic blood pressure, loss of calories
and reduction in body weight, resulting in additional cardiovascular bene
5-9
For those patients with heart failure, the osmotic diuresis created leads to a reduction in volume and systolic blood pressure,
and a lower preload and afterload. This can have positive e
5,9

Side e

https\://app.geekymedics.com/osce-guides/prescribing/prescribing-sodium-glucose-co-transporter-2-sglt2-inhibitors/ 1/411/13/24, 7\:44 PM Guide | Prescribing sodium-glucose co-transporter 2 (SGLT2) inhibitors

Hypoglycaemia

Hypoglycaemia can occur with SGLT2 inhibitors when used in combination with a sulphonylurea or insulin.
1

Infection

The increased urinary excretion of glucose can result in an increased risk of urinary tract and fungal infections.
1
Fournier's gangrene
Although rare, SGLT2 inhibitors are associated with potentially life-threatening Fournier’s gangrene.
Patients must be counselled that if they experience severe pain, tenderness, erythema or swelling in the genital or
perineal area, along with fever or malaise, they must seek urgent medical attention.
SGLT2 inhibitors must be stopped if suspected and appropriate treatment initiated.
1,16

Volume depletion

this is corrected.
1
Osmotic diuresis can lead the patient to volume depletion. Treatment with SGLT2 inhibitors should be temporarily held while

Diabetic ketoacidosis

Patients on SGLT2 inhibitors are at risk of diabetic ketoacidosis (DKA) with an atypical presentation of blood glucose only
moderately elevated (\<14mmol/L). Patients must be informed of the signs including\:
rapid weight loss
nausea and vomiting
abdominal pain
fast and deep breathing
drowsiness
sweet smelling breath
sweet/metallic taste
di
If they experience any of these, they must seek medical attention.
Patients are at higher risk of DKA when they have\:
a low beta cell function reserve
dehydrated
restricted food intake
sudden reduction in insulin
increased insulin requirement such as acute illness, surgery or alcohol abuse
If DKA is suspected, ketones must be tested even if plasma glucose appears normal, the SGLT2 inhibitor discontinued, and
alternatives considered for future management.
As a result of the DKA risk, patients hospitalised for surgery or experiencing an acute illness should have their SGLT2 inhibitor
temporarily withheld until stabilised. 1, 10,11 12
Patients should apply the ‘sick day rules’ in this situation.
The risk of DKA in those patients prescribed an SGLT2 inhibitor for heart failure without diabetes is thought to be minimal,
however there have been case reports in the literature and so caution should be taken if a patient presents with suspected
symptoms.
13-15

Lower limb amputation

Canagli
Appropriate foot care is essential for those with type 2 diabetes, but in addition they should stay well hydrated and seek
medical attention if they experience skin ulceration, discolouration or have any new foot pain or tenderness.
17,18
https\://app.geekymedics.com/osce-guides/prescribing/prescribing-sodium-glucose-co-transporter-2-sglt2-inhibitors/ 2/411/13/24, 7\:44 PM Guide | Prescribing sodium-glucose co-transporter 2 (SGLT2) inhibitors
Patients with risk factors for amputation, including previous amputations, peripheral vascular disease or neuropathy, need extra
monitoring. If a patient develops signi
canagli
Whilst the evidence at present is for canagli
e
1,18

Key interactions

SGLT2 inhibitors can increase the risk of hypoglycaemia when used in combination with other agents for type 2 diabetes such
as sulphonylureas or insulin.
1
The osmotic diuresis increases the risk of hypotension with other medication such as those for hypertension or diuretics.
1
Canagli
enzymes and transport proteins such as carbamazepine, rifampicin, phenytoin and phenobarbital, which can decrease the
body’s exposure to them and therefore e
1,6,7
All SGLT2 inhibitors may increase the renal excretion of lithium and decrease therapeutic levels, therefore closer monitoring
of serum lithium concentrations are required after initiating an SGLT2 inhibitor and if a dose is changed.
5-8

Monitoring

Creatinine levels can increase during treatment, although it should be transient or reversible on stopping. Therefore, renal
function needs close monitoring and should be undertaken at least at baseline and annually thereafter.
1
If a patient has been hospitalised with an acute serious illness or has major surgery, the MHRA advises that blood ketones are
monitored whilst SGLT2 inhibitors treatment is withheld to aid identi
blood ketone levels are normal, treatment can then be restarted.
10,11

References

1. Joint Formulary Committee. B N F 8 6 . 2023
2. NICE. Type 2 diabetes in adults\: management. June 2022. Available from\: [LINK]
3. NICE. EmpagliLINK]
4. DapagliLINK]
5. AstraZeneca. Summary o f P r o d u c t C h a r a c t e r i s t i c s , F o r x i g a . March 2024. Available from\: [LINK]
6. Menarini Farmaceutica Internazionale SRL. S u m m a r y o f P r o d u c t C h a r a c t e r i s t i c s , I n v o k a n a . October 2023. Available from\: [LINK]
7. Boehringer Ingelheim Limited. S u m m a r y o f P r o d u c t C h a r a c t e r i s t i c s , J a r d i a n c e . September 2023. Available from\: [LINK]
8. Merck Sharp & Dohme (UK) Limited. S u m m a r y o f P r o d u c t C h a r a c t e r i s t i c s , S t e g l a t r o . April 2022. Available from\: [LINK]
9. Padda IS, Mahtani AU, Parmar M. Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors. StatPearls Publishing, June 2023.
Available from\: [LINK]
10. Medicines and Healthcare products Regulatory Agency. SGLT2 inhibitors\: updated advice on the risk of diabetic ketoacidosis.
April 2016. Available from\: [LINK]
11. Medicines and Healthcare products Regulatory Agency. SGLT2 inhibitors\: monitor ketones in blood during treatment
interruption for surgical procedures or acute serious medical illness. March 2020. Available from\: [LINK]
12. Diabetes UK. Diabetes when you’re unwell. December 2023. Available from\: [LINK]
13. Raven LM, Muir CA, Green
diabetes. T h e M e d i c a l J o u r n a l o f A u s t r a l i a . August 2023. Available from\: [LINK]
14. Umapathysivam MM, Gunton J, Stranks SN, Jesudason D. Euglycemic Ketoacidosis in Two Patients Without Diabetes After
Introduction of Sodium–Glucose Cotransporter 2 Inhibitor for Heart Failure With Reduced Ejection Fraction. D i a b e t e s C a r e .
Volume 47 (1) January 2024. Available from\: [LINK]
15. Hayes AG, Raven LM, Viardot A, Kotlyar A, Green
D i a b e t e s C a r e . Volume 47 (1) January 2024. Available from\: [LINK]
16. Medicines and Healthcare products Regulatory Agency. SGLT2 inhibitors\: reports of Fournier’s gangrene (necrotising fasciitis of
the genitalia or perineum). February 2019. Available from\: [LINK]
https\://app.geekymedics.com/osce-guides/prescribing/prescribing-sodium-glucose-co-transporter-2-sglt2-inhibitors/ 3/411/13/24, 7\:44 PM Guide | Prescribing sodium-glucose co-transporter 2 (SGLT2) inhibitors
17. Diabetic foot problems\: prevention and management. October 2019. Available from\: [LINK]
18. Medicines and Healthcare products Regulatory Agency. SGLT2 inhibitors\: updated advice on increased risk of lower-limb
amputation (mainly toes). March 2017. Available from\: [LINK]
Source\: geekymedics.com
https\://app.geekymedics.com/osce-guides/prescribing/prescribing-sodium-glucose-co-transporter-2-sglt2-inhibitors/ 4/4