FDA Approves Expanded Uses for Type 2 Diabetes Drugs

Miriam E. Tucker

March 01, 2019

New approvals from the US Food and Drug Administration (FDA) allow expanded use of four already marketed type 2 diabetes treatments.

AstraZeneca announced FDA's approval of the sodium-glucose cotransporter type 2 (SGLT2) inhibitor dapagliflozin (Farxiga) and dapagliflozin + metformin extended release (Xigduo XR) for use in patients with type 2 diabetes and moderate renal impairment, defined as chronic kidney disease with an estimated glomerular filtration rate [eGFR] of 45-59 mL/min/1.73 m2. The previous label had restricted use of the medication to patients with eGFR 60 mL/min/1.73m2 and above.

Approval for the new indication is based on results of the 24-week DERIVE study of 321 patients with inadequately controlled type 2 diabetes and eGFR 45-59 mL/min/1.73m2.

Dapagliflozin alone or combined with metformin is still not recommended when eGFR is less than 45 mL/min/1.73m2 and remains contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73 m2) or end-stage renal disease, or on dialysis.

The new indication brings dapagliflozin in-line with other SGLT2 inhibitors, as both doses of empagliflozin (Jardiance, Lilly/Boehringer Ingelheim) are recommended for use in patients with eGFR ≥45 mL/min/1.73m2, as is the 100-mg dose of canagliflozin (Invokana, Janssen).

Ertugliflozin (Steglatro, Merck/Pfizer), however, is not recommended in patients with eGFR below 60 mL/min/1.73m2

Broadening Use of Combination Basal Insulin/GLP-1 Agonists

Previously approved as an add-on to diet and exercise in adults with type 2 diabetes uncontrolled on long-acting insulin or SC injected lixisenatide (Adlyxin, Sanofi), the FDA has now additionally approved Sanofi's single-injection product, insulin glargine/lixisenatide (Soliqua), for use in patients uncontrolled on oral antidiabetic medicines.

Similarly, FDA has granted the same label expansion to a rival product, Novo Nordisk's basal insulin/glucagon-like peptide 1 (GLP-1) agonist combination of insulin degludec/liraglutide (Xultophy), again allowing use as an adjunct to diet and exercise and removing the requirement that patients already be taking the basal insulin or SC liraglutide (Victoza).

The new indications for Soliqua and Xultophy mean they are technically approved for use in virtually any patient with type 2 diabetes.

Similar additional indications for both agents are already approved in the EU.

SGLT2 Inhibitors Investigated for Patients With Chronic Kidney Disease

The three leading SGLT2 inhibitors are also being investigated in large outcome trials in patients with chronic kidney disease.

AstraZeneca is evaluating the effect of dapagliflozin on renal outcomes and cardiovascular mortality in patients with chronic kidney disease (Dapa-CKD) in 4000 patients with baseline eGFR between 25 and 75 mL/min/1.73m2 (CKD Epidemiology Collaboration formula). Results are due in November 2020.     

Similarly, ongoing in the same patient population is Boehringer Ingelheim and Lilly's study of empagliflozin (EMPA-KIDNEY), which is enrolling 5000 patients with severe to moderate CKD (down to eGFR 20 mL/min/1.73mand examining both kidney disease progression and cardiovascular death. Results are expected in June 2022. 

In addition, the trial evaluating the effects of canagliflozin on renal and cardiovascular outcomes in patients with diabetic kidney disease (CREDENCE), involving 4402 participants with an estimated eGFR down to 30 mL/min/1.73m², was halted in July 2018 because of positive results.

The full CREDENCE results are due to be reported in April at the International Society of Nephrology World Congress of Nephrology in Melbourne, Australia.

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