Will AstraZeneca's SGLT2-favoring data win the class a shot at front-line diabetes use?

Farxiga
AZ's Farxiga is joined in the SGLT2 class by Johnson & Johnson's Invokana and Boehringer and Lilly's Jardiance.

SAN DIEGOBack in March, a real-world analysis showed that SGLT2 diabetes meds from AstraZeneca, Johnson & Johnson and the Eli Lilly-Boehringer Ingelheim team could dramatically cut down on heart failure hospitalizations and deaths. Now, new analyses have confirmed those findingsand may make a case for using the class earlier in treatment, AZ’s execs suggest.

In an oral presentation Tuesday at the American Diabetes Association’s annual meeting, investigators showed that the benefits seen in the real-world undertakinga 300,000 patient study dubbed CVD-REALheld true for Type 2 diabetes patients across the cardiovascular disease spectrum.

RELATED: Diabetes meds from AZ, J&J and Lilly sharply cut death rates in real-world analysis

Researchers separated patients into two groups, one with existing CV disease and the other without. They saw “the same signal, just as robust, in those two different patient populations in terms of the SGLT2 class lowering the risk of hospitalizations for heart failure and death as well,” Jim McDermott, AstraZeneca’s Medical Affairs lead for diabetes, said in an interview.

It’s good news for SGLT2 drugmakers but particularly for AstraZeneca, which, unlike its peers, doesn’t yet have outcomes data in hand showing its entrant can pare down CV risks. The way Mike Crichton, the company’s head of cardiovascular and metabolic diseases, sees it, after CVD-REAL, AZ’s forthcoming outcomes results will be “additive.”

Those data, from the pharma’s Declare study, will build on “the mountain of evidence that we already have with Farxiga that says it does the fundamentals well in the clinic, but it also has a meaningful impact in things like reductions in hospitalizations for heart failure and all-cause mortality,” he said in an interview.

Other analyses presented during the conference also pointed in favor of the SGLT2s. In one Nordic study, meds from the class spurred a 62% reduction in the rate of hospitalization for kidney disease, a 37% reduction in hospitalization for heart failure and a 27% reduction in death by any cause versus DPP-4 inhibitors, a class led by Merck giant Januvia.

As McDermott pointed out, with Farxiga controlling the SGLT2 market in the countries involved, “probably 92, 93, 94% of those patients” involved in the study were on AZ’s med.

Crichton figures those results are reason enough for clinicians to think about “getting Type 2 diabetics off to a strong start with a drug like Farxiga,” he said.

Instead of leading with Januvia and its peers, “you can have a drug that not only knocks down A1C”a key measure of blood glucose—"very effectively but reduces blood pressure and weight,” he said, adding, "DPP-4s, they have some utilization, but certainly we need to start talking about using drugs like Farxiga front-line instead of waiting to save the best for last.”

It’s really more of a shift in the treatment paradigm,” McDermott added. “It’s no longer all about A1C, and I don’t think patients should tolerate that it’s all about A1C anymore. ... I think what you’re seeing is a class of drugs that could really change a treatment paradigm for patients with diabetes and comorbidities.”

Merck, on the other hand, doesn’t expect to see DPP-4s overtaken anytime soon, despite its plans for its own SGLT2 candidate, ertugliflozin. “DPP-4s have had a long history,” Sam Engel, M.D., Merck Research Laboratories’ associate VP of cardiometabolic and women’s health, said in an interview, noting that they “really remain a preferred option for patients who are not achieving goals on metformin.”

Both drugmakers agree, however, that combining the two classes is a good option for those who need extra help in the glucose-lowering departmentand both boast tandem solutions to help get that done. Merck’s pairing of ertugliflozin and Januvia is currently awaiting FDA approval, while AstraZeneca’s Qtern, which marries Farxiga and DPP-4 Onglyza, won FDA approval in February.