FDA approves first triple combination pill for type 2 diabetes
The FDA on Monday approved the first oral therapy to combine three type 2 diabetes medications into one pill: the SGLT2 inhibitor empagliflozin, the DPP-IV inhibitor linagliptin and metformin hydrochloride extended release, according to a press release from Boehringer Ingelheim and Eli Lilly and Co.
The triple combination therapy (Trijardy XR) is approved to lower blood glucose for adults with type 2 diabetes along with diet and exercise.
“Many adults living with type 2 diabetes who are already on a treatment plan including multiple medications still struggle to keep their blood sugar under control, and may require additional agents to reach their [HbA1c] targets,” Ralph A. DeFronzo, MD, director of the diabetes research unit at the University of Texas Health Science Center at San Antonio, said in the release. “Adding new medicines to an individual’s plan can be challenging for some, which is why new treatment options that can help improve blood sugar without the burden of an increased pill count are important. In addition, type 2 diabetes is a complex disease that often requires the use of multiple antidiabetic medications to improve glycemic control. Having three different diabetes medications in a single tablet is an important advance in diabetes treatment.”
In the U.S., empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) and linagliptin (Tradjenta, Boehringer Ingelheim/Eli Lilly) are both once-daily tablets also approved to lower blood glucose for adults with type 2 diabetes. In 2016, the FDA approved a new indication for empagliflozin to reduce the risk for cardiovascular death among adult patients with type 2 diabetes and CVD. In June, the FDA granted fast track designation to empagliflozin for the reduction of risk for CV death and hospitalization for heart failure in people with chronic heart failure.
In findings from the CARMELINA trial presented at the American Diabetes Association Scientific Sessions in June and reported by Healio, researchers found that linagliptin did not increase risks for a new CV event or progression of renal disease among adults with type 2 diabetes, established CVD and renal impairment vs. placebo, regardless of age or the level of renal impairment. Additionally, a head-to-head comparison of the sulfonylurea glimepiride against linagliptin in a cohort of more than 6,000 adults with type 2 diabetes demonstrated no between-group differences for incidence of nonfatal myocardial infarction, nonfatal stroke and CV death during a median of 6 years, according to data from the CAROLINA trial, also reported at ADA.
The triple combination therapy is not indicated for adults with type 1 diabetes or diabetic ketoacidosis and has not been studied in people with a history of pancreatitis. The labeling for Trijardy XR contains a warning for lactic acidosis, a rare but serious complication that can occur due to metformin accumulation, and is common to all products containing metformin, according to the release.
The approval of Trijardy XR is based on two randomized open-label trials that assessed the bioequivalence of empagliflozin, linagliptin and metformin ER fixed-dose combination tablets and their individual components among healthy adults. The safety profile of Trijardy XR was found to be consistent with its individual components.
“The approval of Trijardy XR reflects our commitment to the diabetes community and to innovation that addresses evolving needs,” Jeffrey Emmick, MD, PhD, vice president of product development at Lilly, said in the release. “We developed Trijardy XR because many people with type 2 diabetes need help managing this complex condition without adding more pills to their treatment plan. We look forward to making this new option available soon.”
Trijardy XR will be available in four dosages: 5 mg empagliflozin/2.5 mg linagliptin/1,000 mg metformin hydrochloride ER; 10 mg empagliflozin/5 mg linagliptin/1,000 mg metformin hydrochloride ER; 12.5 mg empagliflozin/2.5 mg linagliptin/1,000 mg metformin hydrochloride ER; and 25 mg empagliflozin/5 mg linagliptin/1,000 mg metformin hydrochloride ER. – by Regina Schaffer
Disclosures: DeFronzo reports that he has served on the advisory board for Astra Zeneca, Novo Nordisk, Janssen, Boehringer-Ingelheim and Intarcia; received honorarium from Elcelyx and Astra Zeneca; received research support from Boehringer-Ingelheim, Astra Zeneca and Janssen; received a research grant from Merck and served on the speaker’s bureau for Novo Nordisk. Emmick is vice president of product development at Lilly.