Based on major clinical trial evidence of SGLT-2 inhibitors for cardiorenal protection, the smallest labelled dose of SGLT-2 inhibitors would be sufficient to achieve this target.
The current indications of the UK-licensed SGLT-2 inhibitors are stated below:
Canagliflozin (Invokana) (11)
1. Canagliflozin is indicated for the treatment of adults with insufficiently controlled type 2 DM as an adjunct to diet and exercise:
- As monotherapy when metformin is considered inappropriate due to intolerance or contraindications
- In addition to other medicinal products for the treatment of diabetes
For this indication, canagliflozin should be initiated at a dose of 100 mg. If further glycaemic control is required, the dose can be increased to 300 mg a day if estimated glomerular filtration rate (eGFR) of above 60 mL/min/1.73m2.Once the eGFR has moved below 60 mL/min/1.73m2 the dose should be reduced to the 100 mg dose and the treatment stopped if the eGFR drops below 30 mL/min/1.73m2. Furthermore because of the low glycaemic effectiveness if the eGFR drops below 45 mL/min/1.73m2 then additional glycaemic lowering medication may be required.
2. For treatment of diabetic kidney disease as add on to standard of care (e.g. angiotensin-converting enzyme inhibitors [ACEi] or angiotensin-II receptor blockers [ARBs]).
Initiation can occur down to an eGFR 30 mL/min/1.73m2. If urinary albumin-to-creatinine ratio (uACR) is >33.9 mg/mmol, canagliflozin can be continued, if started for this indication, down to the need to commence dialysis or renal transplantation.
Dapagliflozin (Forxiga) (12)
1. Dapagliflozin is indicated in adults for the treatment of insufficiently controlled type 2 DM as an adjunct to diet and exercise:
- As monotherapy when metformin is considered inappropriate due to intolerance
- In addition to other medicinal products for the treatment of type 2 DM
For this indication, dapagliflozin can be initiated at a dose of 10 mg. In people with diabetes mellitus, the glucose lowering efficacy of dapagliflozin is reduced when eGFR is < 45 mL/min/1.73m2, and is likely absent in people with severe renal impairment. Therefore, if eGFR falls below 45 mL/min/1.73m2, additional glucose lowering treatment should be considered in people with diabetes mellitus.
2. Dapagliflozin is indicated in adults for the treatment of symptomatic chronic heart failure.
3. Dapagliflozin is indicated in adults for the treatment of CKD.
It is not recommended to initiate treatment with dapagliflozin in people with an eGFR < 15 mL/min/1.73m2.
Empagliflozin (Jardiance) (13)
1. Empagliflozin is indicated in adults for the treatment of insufficiently controlled type 2 DM as an adjunct to diet and exercise:
- As monotherapy when metformin is considered inappropriate due to intolerance
- In addition to other medicinal products for the treatment of diabetes
When used for treatment of insufficiently controlled type 2 DM, empagliflozin should be initiated at a dose of 10mg. If further glycaemic control is required, the dose can be increased to 25 mg a day if above an eGFR of 60 mL/min/1.73m2. If the eGFR drops between 30 and 60 mL/min/1.73m2 then the dose needs to be reduced to 10 mg a day, and the treatment stopped when the eGFR drops below 30 mL/min/1.73m2.
2. Empagliflozin is indicated in adults for the treatment of symptomatic chronic heart failure.
For treatment of heart failure in people with or without type 2 DM, empagliflozin 10 mg may be initiated or continued down to an eGFR of 20 mL/min/1.73 m2
3. Empagliflozin is indicated in adults for the treatment of chronic kidney disease.
For treatment of chronic kidney disease in people with or without type 2 DM, empagliflozin 10 mg may be initiated down to an eGFR of 20 mL/min/1.73 m2 and continued until the patient reaches end stage kidney failure.
Ertugliflozin (Steglatro) (14)
1. Ertugliflozin is indicated in adults aged 18 years and older with type 2 DM as an adjunct to diet and exercise:
- As monotherapy in people for whom the use of metformin is considered inappropriate due to intolerance or contraindications
- In addition to other medicinal products for the treatment of diabetes
Currently, ertugliflozin can be initiated at a dose of 5mg. If further glycaemic control is required, the dose can be increased to 15 mg a day if above an eGFR of 45 mL/min/1.73m2. Ertugliflozin should not be initiated at an eGFR of <45 mL/min/1.73m2, but if already established on treatment, it may be continued down to an eGFR of 30 mL/min/1.73m2. Treatment should be stopped when the eGFR drops below 30 mL/min/1.73m2.