The Role of the Improving Diabetes Steering Committee
The SGLT2 Inhibitor Class of Medicines
Mechanism of Action
UK Treatment Guidelines
Efficacy Data
Reduction in Glycated Haemoglobin (HbA1c)
Weight Loss
Cardiovascular (CV) Efficacy
Key Published CV RCTs
EMPA-REG OUTCOME Trial [12]
The CANVAS Program [16]
Real-World CV OUTCOME Studies
The EASEL Study [17]
CVD-REAL [18]
Ongoing CV and Renal Studies in T2DM
DECLARE-TIMI 58 [25, 26]
CREDENCE [27, 28]
Safety and Tolerability
Genital Infections
Lower Limb Amputations (LLAs) and Bone Fractures
LLAs
Treatment | Number of individuals | Participants with amputation before treatment exposure | Participants with BKLE amputation after treatment exposure | Incidence rate per 1000 person years |
---|---|---|---|---|
All SGLT2i treatments | 11,567 | 225 | 171 | 1.22 |
Canagliflozin | 73,024 | 139 | 120 | 1.26 |
Dapagliflozin | 39,117 | 76 | 37 | 0.96 |
Empagliflozin | 24,433 | 55 | 25 | 1.39 |
Non-SGLT2i glucose-lowering agent | 226,623 | 722 | 530 | 1.87 |
Bone Fractures
Diabetic Ketoacidosis (DKA)
Acute Illness
T2DM Sick Day Rules [43, 44]
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Contact their diabetes team if they are unsure about what to do,
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Stay well hydrated (3 l fluid/day) and eat little and often,
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Keep taking insulin and/or most other diabetes medications, but stop taking SGLT2i, metformin and GLP-1 RA medicines if they are unable to eat or drink, and contact their diabetes team for further directions,
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If possible, keep a close record of blood glucose levels, at least every 4 h, including during the night,
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If the blood glucose level is ≥ 15 mmol/l, urine/blood checks should be conducted to test ketone levels. Medical assistance should be sought when urine ketone levels are > 2 +/or blood ketone levels are > 3 mmol/l,
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Maintain a normal meal pattern (where possible). If unable to eat or appetite is reduced, meals may be replaced with high-carbohydrate snacks or drinks (e.g. fruit juice, glucose tablets),
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If vomiting, drowsy, unable to keep fluids down or suffering with persistent diarrhoea, medical help should be sought immediately.
Considerations When Initiating SGLT2i Therapies at an Early or Late Stage in the T2DM Treatment Pathway
Steering Committee Advice Regarding the Prescribing of SGLT2i Treatments for People Receiving Diuretic Medicines1
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Check electrolyte and renal function for all indviduals prescribed SGLT2is. This is particularly important for people on diuretic therapies.
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Conduct regular electrolyte and renal function measurements, as appropriate for individual circumstances, comorbidities and concomitant medications. A modest reduction in eGFR may be expected following the initiation of SGLT2i therapy, as is the case for other medications such as ACEis.
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Consider reducing or stopping diuretic medicines for treatment of oedema or hypertension, especially if blood pressure is well controlled.
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In line with NHS Scotland 2018 Polypharmacy Guidance, review medicines regularly and de-escalate therapy where possible [48].
Summary and Practical Considerations
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Low risk (green) A robust evidence-base supports SGLT2i prescribing in these situations.
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Moderate risk (amber) Prescribe SGLT2i agents with caution (some evidence supporting a benefit in these circumstances).
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High risk (red) Do not prescribe SGLT2is in these situations (due to a lack of evidence, high risk of AEs, or licence restrictions).
Grade level | Description |
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A | Clear evidence from well-conducted, generalisable RCTs that are adequately powered, including |
Evidence from a well-conducted multicentre trial or meta-analysis that incorporated quality ratings in the analysis | |
Compelling non-experimental evidence | |
B | Supportive evidence from well-conducted cohort studies |
Supportive evidence from a well-conducted case-control study | |
C | Supportive evidence from poorly controlled or uncontrolled studies |
Conflicting evidence with the weight of evidence supporting the recommendation | |
E | Expert consensus or clinical experience |