Table 3 Summary of Recommendations for Implementation

PEOPLE WITH OR WITHOUT DM (excluding TYPE 1)

Grade

1

We recommend using SGLT-2 inhibitors with demonstrated efficacy for their given indications

1A

2

We recommend using clinically appropriate single agent renin-angiotensin-system (RAS) blockade in combination with SGLT-2 inhibition, wherever RAS blockade is indicated and tolerated

1A

3

We suggest following NICE guidelines on use of uACR for screening of albuminuria (NICE NG203). We recognise that more pragmatic approaches to identifying risk of kidney disease progression may be necessary whilst local access to uACR measurement is improved

2C

4

We recommend that SGLT-2 inhibition can be continued until the need for dialysis or kidney transplantation arises

1A

5

We suggest that co-prescription of SGLT-2 inhibition with mineralocorticoid receptor antagonists (MRA) can be considered, where each are individually indicated

2B

6

We suggest the beneficial effects of SGLT-2 inhibition on kidney disease progression or risk of heart failure hospitalisation are likely to be a class effect

2B

DIABETIC KETOACIDOSIS

1

We recommend that people with type 1 DM should only have SGLT-2 inhibitors initiated under the strict direction of the diabetes team

1C

2

We recommend that people with type 2 DM at greater risk of diabetic ketoacidosis (DKA; defined in Table 5a.1 of the supplementary appendix) should have SGLT-2 inhibitors initiated with caution after discussion with the diabetes team

1C

3

We recommend SGLT-2 inhibitors are discontinued when an individual develops DKA

1A

4

We suggest that after an episode of DKA and where a clear contributing factor has been identified, there should be discussion with the person and clinical team to establish whether the benefits of re-introducing an SGLT-2 inhibitor outweigh the risks

2D

5

When initiating SGLT-2 inhibitors, we suggest that individuals should be advised on the signs and symptoms of DKA and be instructed to temporarily withhold SGLT-2 inhibitors and to seek immediate medical advice if symptoms develop

1C

6

We recommend always offering advice on sick day guidance when initiating SGLT-2 inhibitors and reminding them of this at every medication review

1C

7

We suggest that individuals taking SGLT-2 inhibitors should be advised against following a ketogenic diet

2C

8

We suggest that for people who choose to intermittently fast (e.g. for Ramadan), and particularly for those who are elderly, on diuretics or have CKD, consider withholding SGLT-2 inhibitors for the duration of the fasting period and for those people with diabetes ketone testing should be undertaken if unwell

2D

HYPOGLYCAEMIA

1

We recommend considering reducing the dose of insulin/sulphonylureas/meglitinides when initiating SGLT-2 inhibitors to reduce the risk of hypoglycaemia

1C

2

We recommend that when initiating SGLT-2 inhibitors in people taking SUs (e.g. gliclazide) or meglitinides (e.g. repaglinide) when the HbA1c < 58 mmol/mol AND eGFR > 45 mL/min/1.73m², consider reducing dose of SU or meglitinide by 50% to reduce risk of hypoglycaemia

1C

3

We recommend that when starting SGLT-2 inhibitors in people taking insulin when the HbA1c  < 58 mmol/mol AND eGFR > 45 mL/min/1.73m², consider reducing the insulin dose by 20% to avoid hypoglycaemia

1C

4

We recommend that when starting SGLT-2 inhibitors in people taking only metformin ± pioglitazone  ± DPP-4i/gliptins or GLP-1 receptor agonist therapy, no dosage adjustment is necessary

1C

ACUTE KIDNEY INJURY, HYPOVOLAEMIA AND POTASSIUM

1

We recommend that individuals initiated on an SGLT-2 inhibitor do not routinely require an early assessment of kidney function or serum potassium following initiation of treatment

1C

2

We suggest that if an individual has a kidney function assessment within the first few weeks post initiation of an SGLT-2 inhibitor, a decline in eGFR needs to be interpreted with caution and in the context of an expected drug effect to avoid unwarranted discontinuation of treatment

2B

3

We suggest that individuals on diuretics are counselled on the symptoms of hypovolaemia and advised to seek medical attention if they develop any such symptoms after starting SGLT-2 inhibition

2B

4

We suggest that clinicians consider an early clinical review and if appropriate a diuretic or antihypertensive dose reduction in individuals they consider at high risk of hypovolaemia

2C

5

We recommend that SGLT-2 inhibitors are temporarily withheld during acute illness (see sick-day guidance in section 5a.1.2 of the supplementary appendix)

1C

PERIPHERAL VASCULAR DISEASE AND AMPUTATION RISK

1

We suggest avoiding initiation of SGLT-2 inhibitors in the presence of active foot disease (infection, ulceration and ischaemia) and withholding treatment in those who develop foot complications whilst taking an SGLT-2 inhibitor

2B

2

We suggest a shared decision-making approach, with appropriate counselling on risks and benefits of treatment and the importance of routine preventative foot care measures for:

• Individuals at high risk of amputation (previous amputations, existing PVD, peripheral neuropathy)

• Re-initiation of SGLT-2 inhibitors after treatment and satisfactory resolution of a foot complication that occurred whist taking SGLT-2 inhibitors

2B

FRACTURE RISK

1

In people with CKD treated with SGLT-2 inhibitors, we suggest monitoring of bone parameters including calcium, phosphate and PTH should be performed as appropriate for CKD stage (see NICE NG203)

2D

MULTIMORBIDITY AND FRAILTY

1

We suggest an approach to care that takes account of frailty and multimorbidity where these apply. This can include:

• Establishing the person’s goals, values and priorities

• Consideration of the balance of disease and treatment burden (for example, prognostic benefits in people with limited life expectancy or frailty)

• Agreeing an individualised management plan

2D

MYCOTIC GENITAL INFECTIONS AND FOURNIER’S GANGRENE

1

We recommend that all people are counselled on the risks of mycotic genital infections prior to initiation of SGLT-2 inhibitors

1D

2

We recommend that all people are counselled on self-care to maintain good genital hygiene

1C

3

We recommend that all people are counselled on the symptoms of mycotic genital infections and how to seek help including self-management

1D

4

We suggest that for those individuals with a history of recurrent mycotic genital infections on SGLT-2 inhibition, consideration is given to offering prophylactic anti-fungal treatment, which should be reviewed after 6 months of therapy or earlier if clinically indicated

2D

5

We suggest that SGLT-2 inhibitor therapy can be continued during the treatment of mycotic genital infections

2D

6

We highlight the specific MHRA warning and suggest that all people are counselled on the symptoms of Fournier’s gangrene and advised to stop SGLT-2 inhibitors and to seek urgent help if they develop such symptoms

2D

URINARY TRACT INFECTION

1

We recommend temporary discontinuation of SGLT-2 inhibitors when treating acute pyelonephritis or urosepsis (see sick-day guidance in Section 5a.1.2 of the supplementary appendix)

1C

CHILDREN, PREGNANCY AND BREASTFEEDING

1

We suggest that all women of child-bearing potential are counselled, prior to conception, on the risks of SGLT-2 inhibitors during pregnancy

2D

2

We suggest SGLT-2 inhibitor therapy is discontinued upon planning, suspicion or confirmation of pregnancy

2D

3

We suggest SGLT-2 inhibitors are not used in women who are breastfeeding

2D

PEOPLE WITH TYPE 1 DM

1

We recommend that SGLT-2 inhibitors be initiated in people with type 1 DM, only under the strict direction of the diabetes team

1C

2

We suggest considering referring people with type 1 DM to the specialist diabetes team, for consideration of an SGLT-2 inhibitor, if they have an eGFR ≥ 20 mL/min/1.73m², and a uACR ≥ 25 mg/mmol despite being on maximum tolerated ACEi/ARB

2C

3

We recommend all people with type 1 DM started on SGLT-2 inhibitors be provided with ketone monitoring, be advised on the signs and symptoms of DKA and to seek immediate medical advice if any of these symptoms develop or ketone levels are > 0.6 mmol/L

1B

KIDNEY TRANSPLANT RECIPIENTS

1

There is currently insufficient evidence on safety and efficacy to provide Recommendations for use of SGLT-2 inhibition in people with a functioning kidney transplant

-

2

Any use of SGLT-2 inhibition to treat diabetes mellitus in a kidney transplant recipient should be evaluated by multi-disciplinary discussion

2D

ACUTE DECOMPENSATED HEART FAILURE

1

We suggest initiating SGLT-2 inhibition in people with CKD (eGFR ≥ 20 mL/min/1.73m²) with acute decompensated heart failure

2B