From the Journals

Researchers parse which patients with T2D need SGLT2 inhibition



Agents that form the sodium-glucose cotransporter 2 inhibitor class – including canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance) – have show remarkably consistent cardiovascular efficacy and safety for treating patients with heart failure, chronic kidney disease, and higher-risk patients with type 2 diabetes.

Dr. David C. Berg, a cardiologist at Brigham and Women’s Hospital in Boston

Dr. David C. Berg

But despite an essential role now established for drugs in the SGLT2 inhibitor class for patients with heart failure with reduced ejection fraction, progressive renal dysfunction, or – most recently – patients with heart failure with preserved ejection fraction, the scope may be less clear when using these agents in patients with type 2 diabetes because they fall across a broad spectrum of risk for cardiorenal disease.

“What makes patients with type 2 diabetes distinct from other patients in whom SGLT2 inhibitors have been studied, such as patients with heart failure, is that they have a much wider spectrum of risk. Low-risk patients with type 2 diabetes were not included in the SGLT2 inhibitor trials. Defining risk in patients with type 2 diabetes has the potential to inform prioritization” for treatment with an SGLT2 inhibitor, explained David D. Berg, MD, who has led one effort to develop risk scores that can risk-stratify patients with type 2 diabetes based on their vulnerability to incident heart failure and hospitalization for these episodes,

The hefty cost for these drugs, with retail prices that run over $6,000 annually for the most widely used and most potent agents in the class, has spurred researchers to try to find cost-effective ways to identify patients with type 2 diabetes who stand to benefit most from taking an SGLT2 inhibitor.

‘Cost must be considered’

“Cost must be considered, and at this point it’s probably more responsible on a societal level to advise using SGLT2 inhibitors mainly in patients [with type 2 diabetes] with compelling indications,” said Silvio Inzucchi, MD, professor and director of the Yale Medicine Diabetes Center in New Haven, Conn. Dr. Inzucchi added, however, that “I can easily foresee a day when these agents are considered foundational therapy for all patients with type 2 diabetes, after they go generic and cost is not a major issue. I’m starting to lean toward this very simplified approach, but the costs are prohibitive at this time.”

Dr. Silvio Inzucchi, professor and director of the Yale Medicine Diabetes Center in New Haven, Conn.

Dr. Silvio Inzucchi

“If the SGLT2 inhibitors were available at a low cost, I’d argue that they should be used in all patients with type 2 diabetes who have no contraindications or tolerability issues; but we live in a world where they are not yet low cost,” agreed Mikhail N. Kosiborod, MD, a cardiologist and codirector of the Cardiometabolic Center of Excellence at Saint Luke’s Mid-America Heart Institute in Kansas City, Mo.

“We can’t give SGLT2 inhibitors to everyone with type 2 diabetes right now because that would be too costly; these agents are so expensive. You start by targeting the patients with the highest risk” for incident heart failure, said Ambarish Pandey, MD, a cardiologist at the University of Texas Southwestern Medical Center, Dallas.

The spotlight the SGLT2 inhibitor class has received, based on its unexpectedly potent efficacy in cutting rates of acute heart failure episodes in patients with type 2 diabetes, has also sharply raised the profile of this complication of type 2 diabetes, an outcome that until recently many clinicians had largely ignored, overshadowed by a focus on adverse outcomes from atherosclerotic cardiovascular disease such as MIs and strokes.

“Results from the SGLT2 inhibitor trials have reignited interest in the relationship between type 2 diabetes and heart failure and have started to shift the mindset of clinicians toward thinking about reducing both atherothrombotic risk and heart failure risk in patients with type 2 diabetes,” said Dr. Berg, a cardiologist at Brigham and Women’s Hospital in Boston.

“Prior to the SGLT2 inhibitor trials, heart failure was on the radar of diabetes clinicians only as something to watch for as a potential side effect of certain glucose-lowering therapies. Now that there are therapies that can lower heart failure hospitalization, it’s made us think more about heart failure, how common it is in patients with type 2 diabetes, and what can we do to lower this risk,” commented Alice Y.Y. Cheng, MD, a diabetes specialist at the University of Toronto.


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