ACC publishes first-ever consensus statement on novel therapies for type 2 diabetes, recommending GLP-1s and SGLT-2s for CV risk reduction – November 27, 2018

The American College of Cardiology (ACC) yesterday published the first-ever “Expert Consensus Decision Pathway on Novel Therapies for CV Risk Reduction in Patients with Type 2 Diabetes and Atherosclerotic Cardiovascular Disease” (JACC), recommending an SGLT-2 inhibitor or GLP-1 agonist as a second-line approach to lifestyle modification and metformin in patients with established ASCVD and type 2 diabetes.

In a broader sense, the recommendations underscore the need for a collaborative treatment approach and comprehensive CV risk reduction in type 2 diabetes, encouraging cardiologists to: (i) more actively screen for type 2 diabetes in their patients with or at high risk of CV disease; (ii) aggressively treat CV risk factors; and (iii) incorporate data for newer antihyperglycemic agents into routine practice. Moreover, as part of the “major paradigm shift beyond glucose control” for diabetes treatment triggered by GLP-1 agonists and SGLT-2 inhibitors, the publication suggests that cardiologists be incorporated into the broader healthcare provider team of people with type 2 diabetes, which can be fragmented, episodic, and focused on treating acute events (we agree!).

Very notably, these recommendations are endorsed by the ADA and very closely align with those found in the recent ADA/EASD consensus report for managing hyperglycemia in type 2 diabetes. The writing committee includes ADA Chief Medical, Scientific, and Mission Officer Dr. William Cefalu and ADA Family Diabetes Research Award recipient Dr. Rita Kalyani as ADA representatives. We’re thrilled to see ACC publish this extremely important piece, and it should go a long way toward increasing cardiologists’ awareness of and confidence in new diabetes therapies proven to lower CV risk. Doubtless, cardiologists have a key role to play in maximizing uptake of GLP-1s and SGLT-2s, both of which remain highly underutilized for both glucose and CV risk lowering. Following the official launch of AHA and ADA’s multi-year partnership, “Know Diabetes by Heart,” this publication adds to recent momentum in promoting interprofessional collaboration and CV disease awareness among patients with type 2 diabetes, and we salute all organizations involved for taking a collaborative approach.

Treatment Algorithms

The ACC algorithm recommends either an SGLT-2 or GLP-1 with proven CV benefit for those with predominant ASCVD. An SGLT-2 is preferred if heart failure predominates (SGLT-2s should only be used if eGFR is adequate), and a GLP-1 is preferred for substantial weight loss and significant CKD (eGFR<45 mL/min/1.73 m²) – see table below. If clinically indicated, concomitant usage of a GLP-1 agonist and SGLT-2 inhibitor is reasonable in accordance with ADA’s 2018 Standards of Care, though the authors warn of high out-of-pocket costs and possible drug interactions due to opposite effects on glucagon.

• Although the guidelines specify SGLT-2 or GLP-1 use as a second-line therapy, the writers do acknowledge “clinical judgement” may lead some HCPs to prescribe an SGLT-2 or GLP-1 with the intent of reducing CV risk in patients not on background metformin therapy. While they acknowledge the paucity of clinical trial data supporting SGLT-2 or GLP-1 use as a first-line approach, they also assert that background antihyperglycemic therapy (metformin) may arguably not be pertinent to demonstrating comparable CV risk reduction based on what little data is available. We were glad that the authors engaged with metformin’s established role as a foundational therapy – a topic that has garnered significant attention lately – and we’d like to see this debated more. It should also be noted, of course, that a significant number of patients struggle to tolerate metformin.

SGLT-2 Inhibitors

• Lilly/BI’s Jardiance (empagliflozin) is recommended as the preferred SGLT-2 inhibitor based on its indication for reducing CV death in the US. Importantly, these recommendations were constructed before J&J’s Invokana (canagliflozin) received its CV indication in the US, for reducing three-point MACE, as well as prior to the release of full results from the DECLARE CVOT for AZ’s Farxiga (dapagliflozin), which found a statistically significant benefit on the primary composite endpoint of heart failure and CV death. This recommendation is exactly the same as in the ADA/EASD consensus statement, and we’ll be very interested to see how future guidelines relate different SGLT-2 inhibitors to one another.

GLP-1 Agonists

• Novo Nordisk’s Victoza (liraglutide) is recommended as the preferred GLP-1 agonist based on its indication for reducing three-point MACE in the US. Victoza remains the only GLP-1 with a CV indication, though topline REWIND data for Lilly’s Trulicity indicate this will likely change in the near future. Other GLP-1 agonists are not ranked, and this recommendation also aligns with the ADA/EASD consensus statement. In terms of titration, ACC specifically recommends initiating a GLP-1 agonist at the lowest dose and up-titrating slowly to the maximal tolerated dose, in accordance with RCT protocol – an additional detail we don’t often see emphasized in similar figures, perhaps reflecting a continued lack of familiarity with GLP-1 dosing among many cardiologists.

--by Peter Rentzepis, Ann Carracher, and Kelly Close