Ertugliflozine

SGLT2 inhibitor for the treatment of type 2 diabetes mellitus, according to guidelines

see SGLT2 inhibitors

Mechanism of action: SGLT2i are based on a new mode of action that differs fundamentally from insulin and other oral antidiabetics. SGLT2i are based on the selective reversible inhibition of the sodium-dependent glucose transporter SGLT-2 (sodium-glucose co-transporter 2) in the proximal tubule of the kidney. This leads to increased excretion of glucose (glucosuria) and, as the co-transport of sodium is also inhibited, to increased excretion of sodium in the urine (natriuresis). The inhibition is selective for the SGLT-2 transporter. The SGLT-1 transporter is not inhibited. However, the inhibition of SGLT2 is not complete and is also partially compensated by the SGLT-1 transporter further distally in the renal tubule. Therefore, hypoglycemia or electrolyte shifts do not occur.

For further details see SGLT2 inhibitors.

Oral availability, rapid absorption, high plasma protein binding, maximum plasma levels within 1-2 hours, elimination within 24-48 hours after discontinuation.

Metabolized predominantly via glucuronide conjugation via various UDP-glucuronosyltransferase enzymes. Hardly via CYP. Therefore hardly any significant pharmacokinetic interaction with other drugs.

In case of renal dysfunction eGFR ≤45 ml/min glucose-lowering effect reduced, additional glucose-lowering medication may be necessary. The cardio- and nephroprotective effect is maintained even with impaired renal function.

Do not use in the case of severe liver dysfunction or, if necessary, initially use the lowest dose and increase gradually (see the relevant information sheet).

For details, see the prescribing information.

for the treatment of adults aged 18 years and over with inadequately controlled type 2 diabetes mellitus as a supplement and on the basis of lifestyle changes (diet and exercise) in accordance with guidelines:

as monotherapy if metformin is not suitable due to intolerance or contraindications or in addition to other medicines for the treatment of diabetes.

contraindicated during pregnancy and breastfeeding!

Recommended starting dose 5 mg, increase to 15 mg if necessary

Take once a day in the morning regardless of food intake

The most common side effect is an increased risk of genital and urinary tract infections due to glucosuria. The risk can be reduced by good hygiene and care measures. Infections are rare and can generally be treated well with the usual treatment measures.

A serious adverse effect or complication is Fournier's gangrene, a necrotizing fasciitis of the perineum, which occurs very rarely. The risk is increased in patients with immunodeficiency of any cause, poor general health and nutritional status, alcoholism, drug addiction, smoking, advanced age, obesity and others. The disease is life-threatening and requires immediate surgical treatment and debridement.

Complication: Atypical ketoacidosis, very rare but potentially life-threatening! When treated with SGLT2i, ketoacidosis can occur even with only slightly elevated or normal blood glucose levels! Very important and requires special attention in terms of clinic and diagnosis!

Ketoacidosis is very likely if the following symptoms occur: nausea, vomiting, anorexia, abdominal pain, severe thirst, difficulty breathing, confusion, unusual tiredness, drowsiness, loss of consciousness.

Risk is increased in situations with increased endogenous insulin requirement or relative insulin deficiency, such as major surgical interventions (fasting, stress), especially major surgical interventions and bariatric surgery, but also diagnostic procedures that require fasting, low-calorie diets or fasting and dietary changes, especially with reduced carbohydrate intake, low-carb diets, malabsorption, severe fluid loss and excessive physical exertion, excessive alcohol consumption, or acute serious illnesses such as infections, gastroenteritis, myocardial infarction, stroke, etc.etc.
Even with combination treatment of SGLT2i with insulin, reducing the insulin dose can lead to an increased risk of ketoacidosis. Therefore, strict monitoring of blood glucose levels and possibly ketone bodies and increased awareness of symptoms is necessary!

Diagnosis: monitoring of ketone body concentration in blood (ketone body determination in urine not sufficient), pH≤7.3; serum bicarbonate ≤15mmol/l; anion gap ≥12mmol/l.

Immediate discontinuation of SGLT2i and treatment in case of ketoacidosis!

Pause treatment in case of infections and acute illnesses as well as in case of dietary changes, etc. Discontinuation possible 3 days before surgery. (AVP, Arneiverordnung in der Praxis Volume 50(1), March 2023) (patients should be informed about possible ketoacidosis, risk situations and symptoms!)

At the start of treatment, there may be a temporary, reversible increase in serum creatinine and a reduction in eGFR = part of the mode of action and the nephroprotective effect through osmotic diuresis and TGF. In patients with severely impaired renal function, close monitoring and treatment by an experienced nephrologist is recommended (clinical data and studies, as well as guidelines and benefit assessment for the treatment of CKD with low eGFR refer to dapagliflozin and empagliflozin; see Summary of Product Characteristics for the respective product).

Ertugliflozin is not recommended for use at eGFR ≤45 ml/min, and treatment with ertugliflozin should not be given or discontinued at eGFR ≤30 ml/min (see information for healthcare professionals Steglatro, version 2024). Only the treatment of type 2 DM from the age of 18 is specified as an indication for use (see Steglatro information for healthcare professionals, version 2024).

SGLT2i can currently be combined with other medications without any significant, clinically relevant interaction.

When combined with other diuretics (thiazide and loop diuretics), the diuretic effect can be enhanced and the risk of dehydration and hypotension is increased. Particular attention should be paid to elderly patients or patients with a history of hypotension, compensation of dehydration before and during treatment, dose reduction of antihypertensive or diuretic concomitant medication if necessary, pausing SGLT2i and volume compensation if necessary.

In combination with insulin and insulinotropic substances, there is a risk of hypoglycaemia (close blood glucose monitoring necessary, especially when changing the dose, if necessary careful reduction of insulin or other medication, if necessary ketone body monitoring).

There may be increased excretion of lithium and a drop in serum lithium levels (regular lithium levels and, if necessary, dose adjustment at the start of treatment and when changing the dose of SGLT2i).

For detailed information on the special features of the individual substances, please refer to the respective expert information.

not to be used in type 1 diabetes mellitus, as there is too great a risk of life-threatening ketoacidosis.

not to be used in patients under 18 years of age (no data available)

not recommended in renal insufficiency eGFR≤40 ml/min (Information for healthcare professionals Steglatro®, MSD, status 2024);

not to be used in case of hypersensitivity to one of the active substances or other components of the medication. Contains lactose compound, therefore not to be used in patients with rare hereditary galactose intolerance, complete lactase deficiency or glucose-galactose malabsorption.

For further information, see the technical information.

Ertugliflozin ^Steglatro® 5 mg 15 mg

Expert information Ertugliflozin ^Steglatro®