Our COVID-19 information hub has important information for everyone, including resources about vaccines and treatments.
Find out more about the antiviral medicines helping to treat COVID-19.
Medicine Finder
Find information on medicines by active ingredient or brand name
Keep a medicines list
The more medicines you take, the more difficult it can be to remember important information about them.
An independent peer-reviewed journal providing critical commentary on drugs and therapeutics.
Timely, independent, evidence-based information on new drugs and medical tests, and changes to the PBS and MBS.
Medicine Finder
Find information on medicines by active ingredient or brand name
Receive Email Updates
Latest news, evidence and CPD opportunities
Information for consumers on prescription, over-the-counter and complementary medicines.
Provides consumers with a way to report and discuss adverse experiences with medicines
Keep track of medicines and access important health info any time and anywhere, especially in emergencies.
Medicine Finder
Find information on medicines by active ingredient or brand name
Receive Email Updates
Latest news, evidence and CPD opportunities
Independent peer-reviewed journal providing critical commentary on drugs and therapeutics for health professionals
Provides health professionals with timely, independent and evidence-based information
Medicine Finder
Find information on medicines by active ingredient or brand name
Receive Email Updates
Latest news, evidence and CPD opportunities
Our new and ongoing programs for healthcare professionals

Making safe and wise decisions for biological disease-modifying antirheumatic drugs (bDMARDs) and other specialised medicines.

Value in Prescribing — Immunoglobulin products.
Immunoglobulin (Ig) products provide critical therapy for people with immunodeficiencies and immune-type neurological conditions.

Improving clinical practice and health outcomes for Australia.

Provides health professionals with timely, independent and evidence-based information

Ongoing education for Aboriginal and Torres Strait Islander health workers and practitioners on quality use of medicines and medical tests

Practical information, tools and resources for health professionals and staff to help improve the quality of health care and safety for patients
Medicine Finder
Find information on medicines by active ingredient or brand name
Receive Email Updates
Latest news, evidence and CPD opportunities
Relevant, timely and evidence-based information for Australian health professionals and consumers.
Medicine Finder
Find information on medicines by active ingredient or brand name
Receive Email Updates
Latest news, evidence and CPD opportunities
20 years of helping Australians make better decisions about medicines, medical tests and other health technologies
Medicine Finder
Find information on medicines by active ingredient or brand name
Receive Email Updates
Latest news, evidence and CPD opportunities
POPULAR
All fields are required
 
Subscribe to
ACE – angiotensin-converting enzyme
ACR – albumin-to-creatinine ratio
ANCA – anti-neutrophil cytoplasmic autoantibody
ARB – angiotensin receptor II blocker
BP – blood pressure
CKD – chronic kidney disease
CVD – cardiovascular disease
eGFR – estimated glomerular filtration rate
GLP-1 – glucagon-like peptide-1
HbA1c – glycated haemoglobin
KDIGO – Kidney Disease Improving Global Outcomes
NICE – National Institute for Health and Care Excellence
PBS – Pharmaceutical Benefits Scheme
PBAC – Pharmaceutical Benefits Advisory Committee
SGLT2 – sodium–glucose co-transporter-2
The Australasian Proteinuria Consensus Working Group 2012 position statement on proteinuria recommends that the reporting units for albumin-to-creatinine ratio (ACR) should be in mg/mmol.1 Where ACR is referred to in both mg/g and mg/mmol, the article will refer to ACR in the recommended units for the remainder of the article.
On 1 September 2022, a new indication and clinical criteria were added to the General Schedule (Section 85) Authority Required (Streamlined) listing for dapagliflozin (Forxiga).2 It was previously listed only for type 2 diabetes and heart failure.3
The new indication for dapagliflozin is chronic kidney disease (CKD). According to the clinical criteria, the patient must have:2
      that is continued as a combination treatment with dapagliflozin, unless contraindicated.
Patients must not be receiving treatment with another sodium–glucose co-transporter-2 (SGLT2) inhibitor and must discontinue treatment with dapagliflozin prior to initiating kidney replacement therapy (dialysis or kidney transplant).2
Patients not eligible for treatment with dapagliflozin for CKD include those:2
See the PBS website for complete details for this item.
Authorised nurse practitioners may only prescribe continuing therapy of this medicine after it has been initiated by a medical practitioner.2 See the PBS website for more information on nurse practitioner PBS prescribing.
Dapagliflozin belongs to a class of medicines called SGLT2 inhibitors.4,5 Other medicines in this class include:
Dapagliflozin is indicated as 10 mg tablets for proteinuric CKD (stage 2, 3 or 4 and urine ACR ≥ 30 mg/mmol) to reduce the risk of progressive decline in kidney function.5,9
Dapagliflozin is also indicated for adults with:5,10
See the NPS MedicineWise RADAR article Dapagliflozin (Forxiga) for heart failure with reduced ejection fraction (LVEF ≤ 40%) for more information.
SGLT2 is a protein primarily located in the proximal convoluted tubule of the nephrons in the kidneys. It is responsible for resorption of approximately 90% of filtered glucose in the kidneys.11,12
Inhibition of SGLT2 leads to multiple effects, including:11,13,14
SGLT2 inhibition reduces resorption of glucose and also sodium from the glomerular filtrate in the proximal kidney tubule. This leads to urinary excretion of glucose and osmotic diuresis.5,15,16
A key proposed mechanism for renoprotective effects is reduction of intraglomerular pressure through tubuloglomerular feedback.5 In this mechanism, SGLT2 inhibitors cause more sodium to pass along the nephron, which is sensed by macula cells that act via adenosine to constrict afferent glomerular arterioles.15,17
It is proposed that enhanced sodium excretion in the urine (natriuresis) and osmotic diuresis, coupled with reductions in extracellular volume and plasma volume, contribute to the blood pressure (BP)-lowering efficacy of SGLT2 inhibitors, which may preserve kidney function.14
SGLT2 inhibitors may also improve kidney oxygenation and promote anti-inflammatory and antifibrotic pathways, thereby slowing the progression of kidney function decline.18

The 2020 DAPA-CKD trial enrolled 4304 adults from 21 countries, with an eGFR 25–75 mL/min/1.73 m2 and urine ACR 22.6–565 mg/mmol. All participants were on a stable, maximum tolerated dose of standard care (ACE inhibitor or ARB), unless contraindicated, for at least 4 weeks.19
The primary composite outcome was worsening kidney function, defined as a decline of at least 50% in eGFR or onset of kidney failure (dialysis, kidney transplant or GFR < 15 mL/min/1.73 m2), or death due to kidney disease or CVD. This outcome was reduced by 39% with dapagliflozin in comparison to placebo (9.2% with dapagliflozin vs 14.5% with placebo). This corresponds to a number needed to treat of 19 (95% confidence interval [CI] 15 to 27) to prevent one primary outcome event. Sub-group analyses showed that the treatment effect was consistent in patients with and without type 2 diabetes.19
The DAPA-CKD trial also showed a reduced risk of all-cause mortality by 31% with dapagliflozin in comparison to placebo (4.7% with dapagliflozin vs 6.8% with placebo).19

At the March 2022 Meeting, the PBAC recommended listing dapagliflozin for the treatment of CKD.20
The PBAC recognised that there was a high and urgent unmet clinical need for effective CKD treatments, noting that there were limited effective therapies on the PBS specifically for CKD.21
The PBAC was satisfied that dapagliflozin added to standard care provided a significant improvement in efficacy over standard care alone for some patients based on the DAPA-CKD trial. The PBAC considered that dapagliflozin provided a substantial added benefit in terms of a reduction in kidney failure and death.21
The PBAC agreed that dapagliflozin would be an addition to standard care in CKD, administered concurrently with an ACE inhibitor or ARB, unless contraindicated.21
Treatment goals should include pharmacological and lifestyle management22 of the risk factors underlying CKD progression, including hyperglycaemia, hypertension, albuminuria, and obesity.23
Prescribe medicines shown to slow CKD progression and reduce cardiovascular risk.24,25

a Check your patients’ CVD risk using the Australian absolute cardiovascular disease risk calculator.
The clinical place of dapagliflozin (and SGLT2 inhibitors more broadly) in the treatment of people with CKD who do not have type 2 diabetes continues to evolve.14,23
Australian guidelines currently recommend dapagliflozin and other SGLT2 inhibitors as a preferred second-line agent after metformin (unless contraindicated or not tolerated) for patients with CKD and type 2 diabetes to manage blood glucose levels.8,36 The Kidney Disease Improving Global Outcomes (KDIGO) 2020 clinical practical guidelines on management of diabetes in CKD recommend metformin combined with an SGLT2 inhibitor as first-line therapy.29
The United Kingdom NICE guidelines for the treatment of CKD were updated in March 2022, with the recommendation that dapagliflozin be considered as an addition to standard therapy for patients with CKD, with or without type 2 diabetes.37
Following the PBS listing for dapagliflozin to manage CKD in patients with or without type 2 diabetes, the PBAC has estimated there will be an increase in the incidence of diagnosed CKD.38
There are limited post-market safety data for SGLT2 inhibitors in the treatment of CKD in a population without type 2 diabetes. The DAPA-CKD trial showed a lower rate of serious adverse events (severe hypoglycaemia and diabetic ketoacidosis) among people without type 2 diabetes.19
Contraindications
Dapagliflozin should not be used to treat CKD for patients:5,19
Precautions4,5
Pregnancy and breastfeeding
Adverse effects5,34
b Patients with type 2 diabetes are at higher risk of experiencing this adverse effect compared to patients without type 2 diabetes.
The adverse event profile for dapagliflozin for CKD is consistent with other indications such as type 2 diabetes and heart failure. Note that the incidence of adverse effects was higher for patients that had type 2 diabetes compared to those without.37
See the NPS MedicineWise RADAR article Dapagliflozin (Forxiga) for heart failure with reduced ejection fraction (LVEF ≤ 40%) ‘Safety’ section for detailed information about these precautions and adverse effects.
Prescribers and pharmacists are encouraged to discuss the following with patients and carers:4,39
Johnson DW. Medicines shown to slow progression of CKD. Personal Communication. 4 August 2022.
Subscribe to
Reasonable care is taken to provide accurate information at the time of creation. This information is not intended as a substitute for medical advice and should not be exclusively relied on to manage or diagnose a medical condition. NPS MedicineWise disclaims all liability (including for negligence) for any loss, damage or injury resulting from reliance on or use of this information. Read our full disclaimer. This website uses cookies. Read our privacy policy.
©2022 NPS MedicineWise.
Any queries concerning reproduction and rights should be sent to [email protected].
We acknowledge the provision of funding from the Australian Government Department of Health and Aged Care to develop and maintain this website.
PO Box 1147 Strawberry Hills NSW 2012
c/ – Wexted Advisors, Level 17, 68 Pitt St Sydney NSW 2000
ABN: 61 082 034 393
We are always looking for ways to improve our website
Get medicines information:
Report a problem with medicines, medical devices or vaccines:
Please help us to improve our services by answering the following question
0 = Not likely at all
10 = Extremely likely

source

By admin

Leave a Reply

Your email address will not be published. Required fields are marked *