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SGLT-2 Inhibitors Compatible With Most Other Diabetes Meds

Feb 1, 2019
 

New type 2 drug can be used as monotherapy.

Many drugs used for type 2 diabetes come with their share of adverse effects. On the other hand, sodium-glucose cotransporter 2 (SGLT-2) inhibitors are more compatible with many medications for many reasons. Ertugliflozin, currently sold under the brand name Steglatro or in combination with the DPP-4 sitagliptin under the brand name Stegujan or with metformin under the brand name Segluromet, the newest sodium-glucose cotransporter 2 inhibitor approved for type 2 diabetes that can provide fewer of these interactions.1

Ertugliflozin will be the fourth oral, systemic drug in this sodium-glucose cotransporter 2 inhibitor class since its approval in December 2017. People with diabetes would still need to maintain a healthy diet and exercise in addition to using this drug, but other than the lifestyle changes, Ertugliflozin can be used as monotherapy. This is important for many patients if they cannot use or tolerate metformin.1

In addition to monotherapy, Ertugliflozin can be used in combination with other agents used for diabetes, especially with a dipeptidyl peptidase-4 [DPP-4] inhibitor or metformin, combined into one oral tablet. A1C is lowered from ertugliflozin because this agent acts like other sodium-glucose cotransporter 2 inhibitor drugs in that they stop the glomerular filtrate in the kidney from reabsorbing glucose across the apical membrane of the proximal epithelial cells. This causes more glucose to be excreted in the urine.1

The enzymes UGT1A9 and UGT2B will metabolize ertugliflozin the most (CYP3A4, CYP3A5, and CYP2C8 contribute a little). CYP450 isoenzymes (CYP 1A2, CYP 2C9, CYP 2C19, CYP 2C8, CYP 2B6, CYP 2D6, and CYP 3A4) are not inhibited by this agent. And CYP 1A2, CYP 2B6, and CYP 3A4 are not induced by ertugliflozin. The fact that ertugliflozin doesn’t induce nor inhibit many enzymes that other antidiabetic agents do, means that there is much less drug-drug interactions when the patient needs to take medications at the same time as ertugliflozin.1

Multiple studies have demonstrated the efficacy of ertugliflozin in lowering a patient’s A1C. Three studies showed that A1C was lowered even more when ertugliflozin was used in combination with sitagliptin. Individuals who have excess weight or – hypertension may have additional benefits from ertugliflozin. For a benefit in hypertension, the drug increases excretion of sodium (via osmotic diuresis), which decreases the patient’s blood pressure. For the benefit of an individual who has  excess weight, ertugliflozin helps when glucose is excreted because that means a source of calories is being lost, which can result in loss of weight. Studies are already beginning to show weight loss in patients due to ertugliflozin.1

There may be some risks and disadvantages to ertugliflozin as well. So far, it has been found to have the same risks as other agents in its SGLT-2 inhibitor class (i.e., “association with genital mycotic infection, lower-limb amputation, urinary tract infection, acute kidney injury hypotension, and ketoacidosis.”) Also, because this drug is new, it is currently still being evaluated and updated based on reports and studies on its adverse effects. For example, there was a recent safety announcement about a “risk of Fournier’s gangrene,” which is a fatal genital infection, caused by SGLT-2 inhibitor agents (twelve cases since 2013) that will be added to ertugliflozin’s package insert, and monitored for inpatients.

Patients should be educated on reporting “symptoms of redness, swelling, or tenderness of the genital areas accompanied by a fever.” A one-month supply of ertugliflozin monotherapy (30-tablet bottle) costs $321.99 out-of-pocket. Merck has copayment assistance if the patient uses a private insurance.1

Ertugliflozin is already a preferred SGLT-2 inhibitor medication (second or third line for type 2 diabetes in addition to diet and exercise) based on its benefits versus its risks. It has no black box warning [canagliflozin does for its “risk of lower-limb amputation in people with type 2 diabetes and established cardiovascular disease (CVD) ]. But these conditions should still be considered for patients wanting to take ertugliflozin, in addition to renal impairment, recurrent infections; especially in elderly patients.1

Practice Pearls:

  • Ertugliflozin is an SGLT-2 inhibitor that can be used as monotherapy or in combination with the DPP-4 sitagliptin or with metformin.
  • Ertugliflozin has the same mechanism of action and other benefits (and similar risks as other SGLT-2 inhibitors, but it has no black box warnings.
  • Ertugliflozin is already a preferred SGLT-2 inhibitor medication (second or third line for type 2 diabetes in addition to diet and exercise).

Reference:

Nguyen, Vivianne K; White Jr., John R. “Overview of Ertugliflozin.” Clinical Diabetes Journals. 2018. http://clinical.diabetesjournals.org/content/early/2018/11/19/cd18-0097.full-text.pdf. 15 January 2019.

Annahita Forghan, Pharm.D. Candidate 2019, LECOM College of Pharmacy