US FDA approves first oral triple combination therapy for type 2 diabetes
USA: The first oral therapy that combines three medications for type 2 diabetes into one pill, Trijardy XR (Boehringer Ingelheim and Lilly), has received the US FDA's approval to lower blood sugar in adults with type 2 diabetes, along with diet and exercise. The therapy combines empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and metformin hydrochloride (HCl), a biguanide.
Trijardy XR is not for people with type 1 diabetes, or for people with diabetic ketoacidosis (increased ketones in the blood or urine).
"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 A1C targets," said Ralph DeFronzo, professor and diabetes division chief, UT Health San Antonio, said in a press 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."
The approval was based on two randomized open-label trials that assessed the bioequivalence of empagliflozin, linagliptin, and metformin hydrochloride extended-release fixed-dose combination tablets and their individual components in 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," said Jeff Emmick, M.D. Ph.D., vice president, Product Development, Lilly. "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."
Additionally, the approval is supported by a phase 3, randomized, double-blind study that compared the efficacy and safety of empagliflozin plus linagliptin to the individual components as add-on therapy in 686 adult patients with type 2 diabetes who are inadequately controlled on metformin. Patients were randomized 1:1:1:1:1 to receive one of 5 active-treatment arms of empagliflozin 10mg or 25mg, linagliptin 5mg, or linagliptin 5mg in combination with 10mg or 25mg empagliflozin as a fixed-dose combination tablet.
Findings from the study showed that empagliflozin 10mg or 25mg + linagliptin 5mg demonstrated a statistically significant improvement in HbA1c (P <.0001) and fasting plasma glucose (P <.001) compared with the individual components at Week 24. Additionally, a statistically significant reduction in body weight was observed with empagliflozin 10mg or 25mg + linagliptin 5mg compared with linagliptin 5mg alone (P <.0001). No statistically significant difference was observed in body weight compared to empagliflozin alone.
The safety profile of Trijardy XR was consistent with its individual components. The most common adverse reactions include upper respiratory tract infection, urinary tract infection, nasopharyngitis, diarrhea, constipation, headache, and gastroenteritis. It also carries a Boxed Warning for lactic acidosis.
Trijardy XR will be available in four different dosages, including: 5 mg empagliflozin/2.5 mg linagliptin/1000 mg metformin HCl extended-release; 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin HCl extended-release; 12.5 mg empagliflozin/2.5 mg linagliptin/1000 mg metformin HCl extended-release; and 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin HCl extended-release.