Drug reference
Reversibly inhibits sodium-glucose co- transporter 2 (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion. The sulfonylureas act mainly by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta-cell activity is present; during long-term administration they also have an extrapancreatic action.
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Type 2 diabetes mellitus as monotherapy (if metformin inappropriate) | Type 2 diabetes mellitus in combination with insulin or other antidiabetic drugs (if existing treatment fails to achieve adequate glycaemic control) ▶BY MOUTH ▶Adult: 5 mg once daily; increased to 15 mg once daily if necessary and if tolerated, dose to be taken in the morning
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DUE TO INTERACTIONS ▶Manufacturer advises dose of concomitant insulin or drugs that stimulate insulin secretion may need to be reduced.
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Diabetic ketoacidosis Presence of ketoacidosis
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Dehydration. elderly (risk of volume depletion) . heart failure (limited experience). history of hypotension CAUTIONS, FURTHER INFORMATION ▶Volume depletion Manufacturer advises correct hypovolaemia before starting treatment—consider interrupting treatment if volume depletion occurs. Can encourage weight gain. elderly. G6PD deficiency CAUTIONS, FURTHER INFORMATION ▶Elderly Prescription potentially inappropriate (STOPP criteria) if prescribed a long-acting sulfonylurea (e.g. glibenclamide, chlorpropamide, glimepiride) in type 2 diabetes mellitus (risk of prolonged hypoglycaemia). See also Prescribing in the elderly p. 33.
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NICE decisions ▶Ertugliflozin as monotherapy or with metformin for treating type 2 diabetes (March 2019) NICE TA572 Ertugliflozin (Steglatro ®) as monotherapy is recommended as an option for treating type 2 diabetes in adults for whom metformin is contra-indicated or not tolerated and when diet and exercise alone do not provide adequate glycaemic control, only if: . a dipeptidyl peptidase-4 (DPP-4) inhibitor would otherwise be prescribed, and . a sulfonylurea or pioglitazone is not appropriate. Ertugliflozin (Steglatro ®) in a dual-therapy regimen in combination with metformin is recommended as an option for treating type 2 diabetes, only if: . a sulfonylurea is contra-indicated or not tolerated, or . the person is at significant risk of hypoglycaemia or its consequences. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta572 ▶Ertugliflozin with metformin and a dipeptidyl peptidase-4 inhibitor for treating type 2 diabetes (June 2019) NICE TA583 Ertugliflozin (Steglatro ®) with metformin and a dipeptidyl peptidase-4 (DPP-4) inhibitor is recommended as an option for treating type 2 diabetes in adults when diet and exercise alone do not provide adequate glycaemic control, only if: . the disease is uncontrolled with metformin and a DPP-4 inhibitor, and . a sulfonylurea or pioglitazone is not appropriate. Endocrine system Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta583 Scottish Medicines Consortium (SMC) decisions SMC No. SMC2102 The Scottish Medicines Consortium has advised (January 2019) that ertugliflozin (Steglatro ®) is accepted for restricted use within NHS Scotland for the treatment of type 2 diabetes as monotherapy, in patients who would otherwise receive a dipeptidyl peptidase-4 inhibitor and in whom a sulphonylurea or pioglitazone is not appropriate, and as add-on therapy.
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MHRA/CHM ADVICE (UPDATED APRIL 2016): RISK OF DIABETIC KETOACIDOSIS WITH SODIUM-GLUCOSE CO-TRANSPORTER 2 (SGLT2) INHIBITORS A review by the European Medicines Agency has concluded that serious, life-threatening, and fatal cases of diabetic ketoacidosis (DKA) have been reported rarely in patients taking an SGLT2 inhibitor. In several cases, the presentation of DKA was atypical with patients having only moderately elevated blood glucose levels, and some of them occurred during off-label use. To minimise the risk of such effects when treating patients with a SGLT2 inhibitor, the European Medicines Agency has issued the following advice: . inform patients of the signs and symptoms of DKA, (including rapid weight loss, nausea or vomiting, abdominal pain, fast and deep breathing, sleepiness, a sweet smell to the breath, a sweet or metallic taste in the mouth, or a different odour to urine or sweat), and advise them to seek immediate medical advice if they develop any of these . test for raised ketones in patients with signs and symptoms of DKA, even if plasma glucose levels are near-normal . use ertugliflozin with caution in patients with risk factors for DKA, (including a low beta cell reserve, conditions leading to restricted food intake or severe dehydration, sudden reduction in insulin, increased insulin requirements due to acute illness, surgery or alcohol abuse), and discuss these risk factors with patients . discontinue treatment if DKA is suspected or diagnosed . do not restart treatment with any SGLT2 inhibitor in patients who experienced DKA during use, unless another cause for DKA was identified and resolved . interrupt SGLT2 inhibitor treatment in patients who are hospitalised for major surgery or acute serious illnesses; treatment may be restarted once the patient’s condition has stabilised MHRA/CHM ADVICE: SGLT2 INHIBITORS: MONITOR KETONES IN BLOOD DURING TREATMENT INTERRUPTION FOR SURGICAL PROCEDURES OR ACUTE SERIOUS MEDICAL ILLNESS (MARCH 2020) New recommendations have been issued following a European review of peri-operative diabetic ketoacidosis in patients taking SGLT2 inhibitors. Healthcare professionals are advised to monitor ketone levels during SGLT2 inhibitor treatment interruption in patients who have been hospitalised for major surgery or acute serious illness—measurement of blood ketone levels is preferred to urine. Treatment may be restarted once ketone levels are normal and the patient’s condition has stabilised. MHRA/CHM ADVICE: SGLT2 INHIBITORS: REPORTS OF FOURNIER’S GANGRENE (NECROTISING FASCIITIS OF THE GENITALIA OR PERINEUM) (FEBRUARY 2019) Fournier’s gangrene, a rare but serious and potentially life-threatening infection, has been associated with the use of sodium-glucose co-transporter 2 (SGLT2) inhibitors. If Fournier’s gangrene is suspected, stop the SGLT2 inhibitor and urgently start treatment (including antibiotics and surgical debridement). Patients should be advised to seek urgent medical attention if they experience severe pain, tenderness, erythema, or swelling in the genital or perineal area, accompanied by fever or malaise—urogenital infection or perineal abscess may precede necrotising fasciitis.
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→Appendix 1: ertugliflozin
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▶Common or very common Hypoglycaemia (in combination with insulin or sulfonylurea). hypovolaemia. increased risk of infection. polydipsia. thirst. urinary disorders. vulvovaginal pruritus ▶Rare or very rare Diabetic ketoacidosis (discontinue immediately) ▶Frequency not known Fournier’s gangrene (discontinue and initiate treatment promptly). lower limb amputations . phimosis SIDE-EFFECTS, FURTHER INFORMATION Consider interrupting treatment if volume depletion occurs. ▶Common or very common Abdominal pain. diarrhoea. hypoglycaemia. nausea ▶Uncommon Hepatic disorders. vomiting ▶Rare or very rare Agranulocytosis. erythropenia. granulocytopenia. haemolytic anaemia. leucopenia. pancytopenia. thrombocytopenia ▶Frequency not known Allergic dermatitis (usually in the first 6–8 weeks of therapy). constipation. photosensitivity reaction. skin reactions. visual impairment
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Manufacturer advises avoid—toxicity in animal studies.
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Manufacturer advises avoid—present in milk in animal studies.
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Manufacturer advises avoid in severe impairment (no information available). In general, manufacturers advise avoid in severe impairment (increased risk of hypoglycaemia).
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Manufacturer advises avoid initiation if eGFR less than 60 mL/minute/1.73 m2. Manufacturer advises frequent monitoring of renal function required if eGFR less than 60 mL/minute/1.73 m2. Manufacturer advises avoid if eGFR is persistently less than 45 mL/minute/1.73 m2. Sulfonylureas should be used with care in those with mild to moderate renal impairment, because of the hazard of hypoglycaemia. Care is required to use the lowest dose that adequately controls blood glucose. Avoid where possible in severe renal impairment.
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▶Manufacturer advises to determine renal function before treatment and periodically thereafter. ▶Manufacturer advises monitor volume status and electrolytes during treatment in patients at risk of volume depletion.
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There can be variation in the licensing of different medicines containing the same drug. Tablet ▶Steglatro (Merck Sharp & Dohme Ltd) A Ertugliflozin (as Ertugliflozin L-pyroglutamic acid) 5 mg Steglatro 5mg tablets | 28 tablet P £29.40 DT = £29.40 Ertugliflozin (as Ertugliflozin L-pyroglutamic acid) 15 mg Steglatro 15mg tablets | 28 tablet P £29.40 DT = £29.40 BLOOD GLUCOSE LOWERING DRUGS › SULFONYLUREAS Sulfonylureas f
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Manufacturer advises that patients should be informed of the signs and symptoms of diabetic ketoacidosis, see MHRA advice. The risk of hypoglycaemia associated with sulfonylureas should be discussed with the patient, especially when concomitant glucose-lowering drugs are prescribed. Driving and skilled tasks Drivers need to be particularly careful to avoid hypoglycaemia and should be warned of the problems. Endocrine system eiiii F 747
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5 mg once daily; increased to 15 mg once daily if
First-line fragment. Read the complete Indications and Dose section above.
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