Population Health Implications of Cardiorenal Metabolic Syndrome

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Pathways involved in cardiovascular, renal, and metabolic function are complex and interconnected. Cardiorenal syndrome (CRS) includes a spectrum of heart and kidney disorders involving dysfunction in 1 organ that leads to dysfunction in another organ.1 The use of sodium-glucose transport protein 2(SGLT2) inhibitors, which originally were indicated for glycemic control in patients given a diagnosis of type 2 diabetes, has improved cardiovascular and renal outcomes both in patients with type 2 diabetes who are at high cardiovascular and/or renal risk and in individuals with cardiovascular disease independent of diabetic status. However, these drugs remain underused in clinical practice. Greater use of SGLT2 inhibitors is needed to optimize care for patients with CRS, according to stakeholders who participated in a recent AJMC® Peer Exchange™panel moderated by Neil Minkoff, MD, chief medical officer of Coeus Healthcare and Consulting in Sudbury, Massachusetts.

OVERVIEW OF CRS

Formal definitions of CRS have evolved over time and have varied slightly among reviews by
professional societies.

In 2008, the Consensus Conference of the Acute Dialysis Quality Initiative classified CRS into 5 phenotypes based upon the acuity of disease and sequence of organ involvement1:

Type 1: Acute CRS, with heart failure resulting in acute kidney injury;

Type 2: Chronic CRS, with chronic heart failure resulting in chronic kidney disease;

Type 3: Acute renocardiac syndrome, with acute kidney injury resulting in acute heart failure;

Type 4: Chronic renocardiac syndrome, with chronic kidney disease resulting in chronic heart failure; and

Type 5: Secondary CRS, with a systemic process resulting in heart and kidney failure.

The pathophysiologic mechanism of CRS is believed to result from the heart’s inability to generate sufficient blood flow, which would lead to prerenal hypoperfusion and subsequent activation of the renin-angiotensin-aldosterone system axis, sympathetic nervous system, and arginine vasopressin secretion. These changes, in turn, would lead to fluid retention, greater preload on the heart, and worsened heart-pump failure.1 However, CRS pathophysiology extends beyond hemodynamics and involves multiple neurohumoral and inflammatory pathways.1 Additionally, identifying the primary cause of, and subsequent events leading to, CRS can be challenging because they often involve medical conditions associated with multiple interconnected pathways that feature poorly defined temporal patterns of progression. These conditions include diabetes, hypertension, heart failure, atherosclerosis, endothelial cell dysfunction, anemia and iron metabolism disorders, and chronic inflammation.1

Chronic kidney disease and cardiovascular disease are commonly noted among patients with type 2 diabetes.2 In adults with type 2 diabetes identified in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2012, the overall prevalence of chronic kidney disease was 43.5% (95% CI, 41.6%-45.4%) based on estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration equation or albuminuria criteria.3 A systematic review of 57 studies from around the world, which collectively involved more than 4.5 million individuals with type 2 diabetes, showed that cardiovascular disease had an overall prevalence of 32.2% and accounted for 50.3% of all deaths in this population.4

Type 2 diabetes is also strongly linked to development of CRS.2 Data from the NHANES showed that individuals who received a diagnosis of diabetes had a higher rate of chronic kidney disease than did those who were not given this diagnosis (14.7% vs 6.3%, respectively); the odds ratio (OR) for chronic kidney disease was higher among individuals with cardiovascular disease and diabetes after adjusting for medical and demographic risk factors (OR, 2.25; 95% CI, 1.56-3.23; P < .05).5 Women accounted for 67.9% of patients with chronic kidney disease; further, 73.6% of individuals aged 80 years or older had chronic kidney disease.5

Additionally, control of diabetes and related risk factors has stalled and declined since the early 2010s, according to a recent cross-sectional analysis of data from the NHANES.6 The proportion of patients who achieved a glycated hemoglobin target of less than 7% was 44.0% (95% CI, 38.9-49.3) from 1999 to 2002; it increased to 57.4% (95% CI, 52.9-61.8) from 2007 to 2010 and then decreased to 50.5% (95% CI,45.8-55.3) from 2015 to 2018.6 The proportion of patients who achieved the cutoff for blood pressure control of less than 140/90 mm Hg showed similar trends and was 64.0% (95% CI, 59.2-68.5) from 1999 to 2002, 74.2% (95% CI, 70.7-77.4) from 2011 to 2014, and 70.4% (95% CI, 66.7-73.8) from 2015 to 2018.6 The proportion of patients who achieved the lipid control cutoff (non-high density lipoprotein–cholesterol level < 130 mg/dL) was 25.3% (95% CI, 20.8-30.4) from 1999 to 2002; it increased to 52.3% (95% CI, 49.2-55.3) from 2007 to 2010 and then minimally improved to 55.7% (95% CI, 50.8-60.5) from 2015 to 2018.6 The proportion of patients who achieved all 3 goals simultaneously was 9.0% (95% CI, 6.7-11.9) from 1999 to 2002 and 24.9% [95% CI, 21.1-29.0) from 2007 to 2010; it then plateaued at 22.2% (95% CI, 17.9-27.3) from 2015 to 2018.6 These trends corresponded somewhat to trends in the use of first-line medications. The use of glucose-lowering drugs, antihypertensive agents, and statins increased from 1999 to the early 2010s and subsequently leveled off. The study authors concluded that increasing the use of first-line therapies is a critical first step toward success in achieving glycemic targets.6

STAKEHOLDER INSIGHTS

Understanding of the pathophysiology of CRS has evolved from a cardiocentric process to one that involves an interplay of neurohormonal and inflammatory systems with alterations associated with metabolic syndrome and type 2 diabetes. The rising incidence and prevalence of heart failure, diabetes, and chronic kidney disease and the interplay of these conditions has introduced challenges to managing patients given a diagnosis of CRS. Optimal management of this population varies across health systems and institutions; however, collaboration among the patient’s cardiologist, endocrinologist, nephrologist, and primary care doctor is important to ensure that treatment goals complement each other (eg, a nephrologist aiming solely to lower the serum creatinine level may work in opposition to a cardiologist aiming to optimize decongestion and reduce volume load). One stakeholder stated that patients with CRS are “some of the most complex patients that we have,” adding that the risk from heart failure, diabetes, or renal dysfunction is multiplicative, not additive. Additionally, health care use is high among patients with CRS, and delivery of value-based care by improving coordination along the continuum of care is particularly important.

Although the selection of medications for type 2 diabetes (notably SGLT2 inhibitors and GLP-1 receptor agonists) has increased since 2015; data from the NHANES that showed the recent plateau in the proportion of patients with type 2 diabetes who achieve targets for controlling levels of hyperglycemia, hypertension, and hyperlipidemia levels highlights the need for improved collaboration among providers to optimize overall management. Improved longitudinal care in the outpatient setting is also instrumental for avoiding preventable hospitalizations and emergency department (ED) visits, which are important for both patients with complex needs and their families. Even small efforts—such as implementation of a transition clinic for consultations between diabetes educators, nurse practitioners, patients, and families about care—may reduce the rate of ED visits, according to an unpublished study performed by a stakeholder and his colleagues.

CRS AND THE EMERGING ROLE OF SGLT2 INHIBITORS

Current medical therapies for CRS include a combination of decon­gestive therapies, neurohormonal modulators, vasodilators, ionotropics, inhibitors of the renin-aldosterone-angiotensin system (eg, angiotensin converting–enzyme [ACE] inhibitors and angiotensin receptor blockers [ARBs]), neprilysin/renin-angiotensin inhibitors, and β-adrenergic blockers.1 Patients with type 2 diabetes who also have been given diagnoses of chronic kidney disease and cardiovascular disease are typically managed with lifestyle modification, optimization of glycemic and blood pressure control, and use of ACE inhibitors and ARBs, but the burden of chronic kidney disease and cardiovascular disease often persists even if management is optimal.7

Newer classes of antidiabetic therapies, including SGLT2 inhibitors, represent a paradigm shift in therapeutic strategy for optimizing cardiovascular and renal outcomes in patients with type 2 diabetes, according to a scientific statement from the American Heart Association.7 Additionally, the proposed “Four Pillars of Heart Failure” is a novel conceptual framework that entails parallel implementation of angiotensin receptor-neprilysin inhibitors, β-adrenergic blockers, mineralocorticoid receptors, and SGLT2 inhibitors in patients who have received a diagnosis of heart failure and have a reduced ejection fraction.8

SGLT2 inhibitors, which inhibit glucose reabsorption through the SGLT2 receptors present on the proximal convoluted tubule of the kidneys, are used alone or with other oral anti-hyperglycemic agents to improve glycemic control in patients with type 2 diabetes; their use has produced favorable cardiovascular and renal outcomes in these patients.2 The results of a systematic review and meta-analysis of randomized, placebo-controlled trials that investigated cardiovascular outcomes of patients with type 2 diabetes showed that use of SGLT2 inhibitors reduced the risk of cardiovascular death or hospitalization for heart failure by 23% (HR, 0.77; 95% CI, 0.71-0.84; P < .0001), hospitalization for heart failure by 31% (HR, 0.69; 95% CI, 0.61-0.79; P < .0001), and progression of renal disease by 45% (HR, 0.55; 95% CI, 0.48-0.64; P < .0001) when compared with placebo.9

Although the mechanisms by which SGLT2 inhibitors improve cardiovascular and renal outcomes are still being elucidated, proposed cardioprotective mechanisms of SGLT2 inhibitors include osmotic diuresis, local inhibition of the renin-angiotensin system, a caloric restriction mimicry effect that shifts substrate use from glucose to fat, reduction in arterial stiffness, and improvement in endothelial dysfunction.2 Proposed mechanisms of renal protection include decreases in intraglomerular pressure (via decreased sodium reabsorption in the proximal convoluted tubule and increased sodium transport to the macula densa of the distal juxtaglomerular apparatus), reduction in plasma uric acid levels, inhibition of renal reabsorption of sodium-coupled uric acid in the proximal convoluted tubule, and reduction in oxidative stress.2 The experts believed that the cardiovascular and renal effects are unlikely to be explained solely by the effects of SGLT2 inhibitors on glycemic control because use of other drugs with greater antihyperglycemic effects do not lead to the substantial cardiovascular and renal improvements observed with use of these agents. Further, the improvements are not due entirely to natriuretic effects because SGLT2 inhibitors have a modest effect on plasma volume and circulating natriuretic peptide levels.10

Evolution of the Indications for SGLT2 Inhibitors

In 2014, empagliflozin initially was approved by the FDA as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.11 In 2016, the FDA added an indication for empagliflozin to reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease; this indication was based on results from the EMPA-REG OUTCOME trial (NCT01131676), which showed that empagliflozin therapy was associated with a lower risk for death from cardiovascular causes (HR, 0.62; 95% CI, 0.49-0.77; P < .001), death from any cause (HR, 0.68; 95% CI, 0.57-0.82; P < .001), and hospitalization for heart failure (HR, 0.65; 95% CI, 0.50-0.85; P = .002) when compared with placebo in patients with type 2 diabetes and high cardiovascular risk.12 Assessment of renal outcomes was also a prespecified objective of the EMPA-REG OUTCOME trial, and the empagliflozin group had a lower rate of incident or worsening nephropathy (12.7% vs 18.8% with placebo; relative risk [RR] reduction, 39%), progression to macroalbuminuria (11.2% vs 16.2%, respectively; RR reduction, 38%), doubling of the serum creatinine level (1.5% vs 2.6%, respectively; RR reduction, 44%), and initiation of renal replacement therapy (0.3% vs 0.6%, respectively; RR reduction, 55%).13

Analysis of the CANVAS (NCT01032629) and CANVAS-R (NCT01989754) trials of patients with type 2 diabetes and high cardiovascular risk showed that canagliflozin use was associated with a lower rate of a primary outcome event when compared with placebo (composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; 26.9 vs 31.5 participants with an event per 1000 patient-years [HR, 0.86; 95% CI, 0.75-0.97; P < .001 for noninferiority; P = .02 for superiority]).14 Additionally, progression of albuminuria (89.4 vs 128.7 participants with an event per 1000 patient-years [HR, 0.73; 95% CI, 0.67-0.79]) and the composite outcome of a sustained 40% reduction in eGFR, need for renal replacement therapy, or death from renal causes (5.5 vs 9.0 participants with an outcome per 1000 patient-years [HR, 0.60; 95% CI, 0.47-0.77]) were less frequent among the canagliflozin group.14

These findings on renal outcomes prompted the design of the CREDENCE trial (NCT02065791), which aimed to assess the effects of canagliflozin therapy on renal outcomes in patients with type 2 diabetes and albuminuric chronic kidney disease.15 The rate of the primary composite outcome (end-stage kidney disease, doubling of serum creatinine level, or renal or cardiovascular death) was lower with use of canagliflozin than with placebo (43.2 vs 61.2 events per 1000 patient-years; RR reduction, 30% [HR, 0.70; 95% CI, 0.59-0.82; P = .00001]).15 These findings prompted the FDA approval of an indication for canagliflozin to reduce the risk for end-stage kidney disease, doubling of serum creatinine level, cardiovascular death, and hospitalization for heart failure in patients with type 2 diabetes and diabetic nephropathy with albuminuria.16

Unlike the trials of empagliflozin and canagliflozin in patients with type 2 diabetes, results from the DECLARE-TIMI58 trial (NCT01730534) showed that dapagliflozin therapy was not associated with a lower rate of cardiovascular death when compared with placebo (HR, 0.98; 95% CI, 0.82-1.17), but it was associated with a lower rate of hospitalization for heart failure (HR, 0.73; 95% CI, 0.61-0.88).17 The authors suggested that the differences in outcomes in the dapagliflozin trial may be related to variations in patient characteristics between the DECLARE-TIMI58 trial (which had a minority of patients with atherosclerotic cardiovascular disease and excluded patients with a creatinine clearance < 60 mL/min) and the EMPA-REG OUTCOME trial (which exclusively enrolled patients with atherosclerotic cardiovascular disease and had a high percentage of patients with chronic kidney disease when compared with other SGLT2-inhibitor trials).18

Recent data suggested that use of SGLT2 inhibitors may also improve outcomes of heart failure in patients regardless of their type 2 diabetes status.19-22 Results of the DAPA-HF trial (NCT03036124), which included patients with heart failure and a reduced ejection fraction, showed that the primary composite outcome of worsening heart failure (defined as hospitalization or an urgent visit resulting in intravenous therapy for heart failure) occurred in a smaller proportion of patients who received dapagliflozin than in those who received placebo (16.3% vs 21.2%, respectively [HR, 0.74; 95% CI, 0.65-0.85; P < .001]).19 These findings prompted FDA approval of dapagliflozin to reduce the risk for cardiovascular disease and hospitalization for heart failure in adult patients who have heart failure with a reduced ejection fraction.23

Similarly, the EMPEROR-Reduced trial (NCT03057977) of patients with class II to IV heart failure and an ejection fraction of 40% or less showed that empagliflozin therapy was associated with a lower incidence of the primary composite outcome (ie, death from cardiovascular causes or hospitalization for heart failure) when compared with placebo (HR, 0.75; 95% CI, 0.65-0.86; P < .001); these effects were maintained across prespecified subgroups, including patients who had and had not received a diagnosis of diabetes at baseline.20 Results published in a recent press release concerning the EMPEROR-Preserved trial (NCT03057951) showed that empagliflozin therapy was associated with a significant reduction in the composite outcome of cardiovascular death or hospitalization for heart failure when compared with placebo in patients with heart failure with preserved ejection fraction, a form of heart failure that has no approved therapies (6.9 vs 8.7 events per 100 patient-years, respectively [HR, 0.79; 95% CI, 0.69-0.90; P < .001]).21

Additionally, results from the DAPA-CKD trial (NCT03036150) showed that use of dapagliflozin may be beneficial for patients with chronic kidney disease regardless of type 2 diabetes status.22 The primary composite outcome (sustained decrease in eGFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes) occurred less frequently in the dapagliflozin group than in the placebo group (9.2% vs 14.5%, respectively [HR, 0.61; 95% CI, 0.51-0.72; P < .001]).22 The effect of dapagliflozin on the primary outcome was also consistent across prespecified subgroups, including in patients with type 2 diabetes (HR, 0.64; 95% CI, 0.52-0.79) and those without type 2 diabetes (HR, 0.50; 95% CI, 0.35-0.72).22

However, uptake of SGLT2 inhibitors in clinical practice has been low, according to an analysis of patients with type 2 diabetes who initiated antidiabetic therapy from 2013 to 2019 in 2 large US health insurance databases.24 Although the uptake of SGLT2 inhibitors increased over the study period, use of these agents as first-line treatment for type 2 diabetes was low overall (0.8% of those on Medicare and 1.7% of those on commercial insurance), and the uptake was more evident among commercially insured patients with cardiovascular disease.24

STAKEHOLDER INSIGHTS

Although initially conceptualized as antidiabetic drugs, SGLT2 inhibitors have strong evidence to support their ability to reduce the incidence of cardiovascular disease, heart failure, and progression of chronic kidney disease. The “dramatic” reduction in hospitalizations related to heart failure with SGLT2 inhibitors, regardless of diabetic status, has led to a paradigm shift in guideline-directed therapy to include SGLT2 inhibitors in the armamentarium for CRS.

The stakeholders noted that despite the promise of SGLT2 inhibitors for improving CRS outcomes, the actual use of these agents is less than the number of patients who would derive benefit from therapy—and endocrinologists, nephrologists, cardiologists, and primary care providers involved in managing these patients need to develop care pathways to deliver these therapies to patients. The rapid expansion of indications for SGLT2 inhibitors may complicate a payer’s view of whether 1 agent is superior to another. In addition, payers must decide whether drug price is the primary factor for defining therapeutic value, since the high monetary cost of SGLT2 inhibitors may limit their use. Moving forward, education of primary care physicians is important to clarify misconceptions about data on adverse effects (AEs); these include case reports of diabetic ketoacidosis that tend to occur in patients with type 1 diabetes, rate of mycotic infections, and the original warning on the FDA label (which has since been dropped) about distal amputations of lower extremities observed in patients using canagliflozin.

The siloed and fragmented approach to care may also contribute to delays in the delivery of SGLT2 inhibitors to patients with CRS, particularly if each provider assumes that another member of the patient’s care team is prescribing the drug. Multidisciplinary collaboration among providers is important to help develop care pathways for these patients and ensure that they get prompt treatment with SGLT2 inhibitors.

POPULATION HEALTH IN CRS AND SGLT2 INHIBITORS—STAKEHOLDER INSIGHTS

Jeffrey Turner, MD, associate professor of nephrology at the Yale University School of Medicine in New Haven, Connecticut, said that in his experience, the patients of most concern have advanced heart failure; control of blood pressure often is difficult, and these individuals often do not respond well to diuretics or require high diuretic doses to obtain a response. “They just lack stability, so they need constant monitoring and adjustment of medications,” he said. “The data [have] shown us that the kidney numbers, the creatinine [levels], and, in particular, the day-to-day changes in creatinine [levels], aren’t the most important metric to look at, but looking at their volume management and their heart failure and cardiovascular state is really what drives the prognosis of these patients.”

Many cardiologists, endocrinologists, and nephrologists tend to take an organ-centric approach for management of CRS when a patient-centric view would likely be beneficial for these patients, according to Nihar R. Desai, MD, MPH, associate professor of medicine and
associate chief of the section of Cardiovascular Medicine at the Yale University School of Medicine. “These patients are the very definition of what multidisciplinary team is all about,” he said, “because if you’ve got cardiac disease, you have renal disease, you have metabolic syndrome, or diabetes, and probably, for many of our patients, all of those things. Then what you need is not just 1 person who’s thinking about this part of your body, and another person’s thinking about another part of your body, but someone who’s thinking about the whole person.”

Desai said that his institution has explored use of care navigators on the heart failure component of the equation as well as value-based care programs. This has led to improved collaboration among the payers, health system, and providers of patients with CRS, who tend to be high users of the health care system. “Care coordination [and] some high-value therapies can really go a long way to better outcomes, lower costs, and better value.”

Om P. Ganda, MD, clinical investigator and senior staff physician at the Joslin Diabetes Center and associate clinical professor of medicine at Harvard Medical School in Boston, Massachusetts, said that his institution started a cardiometabolic clinic in conjunction with the Advanced Heart Failure Program at Beth Israel Deaconess Medical Center. He stated that his colleagues and he aim to expand the collaboration to include patients with advanced kidney disease. Like Turner, Ganda said that management of heart failure is the first step when approaching hospitalized patients with CRS. He recommends follow-up soon after discharge and collaboration with the primary care physician to get a patient started on an SGLT2 inhibitor.

Ganda added that despite recent efforts on collaboration with payers, data that shows lower use of SGLT2 inhibitors by patients insured with Medicare than by those having commercial insurance suggest that much work remains to increase use of these agents. Minkoff suggested that patients on Medicare Advantage programs may be more inclined to receive generic medications to reduce health care costs. In addition, Minkoff noted that educating clinicians and patients about the benefits of a highly effective (albeit more expensive) drug (eg, an SGLT2 inhibitor) is important moving forward. “You might pay a little more copay,” Minkoff commented, “but if you avoid 1 hospitalization, you [are] still … ahead of the game.”

As for strategies to increase patient uptake and acceptance, Turner said that ensuring that he has enough time to discuss a new medication (eg, an SGLT2 inhibitor) is important for patient buy-in. “[It is important to have] that time to sit down and really reach out to that patient, explain to them why you are starting them on this medication, because … we’re asking a lot of a patient to start taking a daily medication for presumably the rest of their life,” said Turner. “We underestimate how much we ask patients when we simply prescribe something to their pharmacy. We’re really winning them over and finding where they’re at, and, sometimes, that takes a couple of visits to get them to where they need to be mentally to buy into this medication.”

Desai agreed that taking the time to counsel patients about reasons for modifying a diuretic program and educating them on the benefits and potential AEs of a new medication are key components of patient management. “It’s not just writing the prescription or getting the prescription in through the computer,” he noted. “It’s really got to be about engaging the patient, walking them through the decision. What are the risks? What are the benefits? Why do we think this is so important? How is it going to work? What are the logistics? What other changes do we have to make as kind of a part of a plan here, and how are we going to check in on you and make sure that things are going the way that we want them to go?” He continued, “On the heart failure side, we have a very robust disease management program with advanced practice providers and nurses and pharmacists. What we’ve tried to do is bring that whole team together and empower every member of that team to be part of this—to engage with our patients and to help them get on therapies that we think are going to be important for them from a cardiovascular risk-reduction stand [point].”

However, Ganda said that access to SGLT2 inhibitors may be disproportionately more difficult for certain groups of patients, such as those with low socioeconomic status. “We really need to talk about access,” he said, “… because some of these patients need it the most, and they can’t get it.”

When identifying quality measures to assess the value of care for CRS, Desai said that stakeholders should focus on end points that are relevant to patients (eg, hospitalizations and cardiovascular events that affect quality of life) and measures currently identified in guidelines for patients with cardiovascular disease, diabetes, metabolic syndrome, or renal dysfunction. “If we want to talk about sort of reimagining the quality measurement enterprise to best align the interests of the patient and the interest of providers, payers, systems, and those that are bearing risk providing coverage for those patients, I think that’s a good framework for what a quality metric program should look like here on the cardiometabolic and cardiorenal side of things,” he noted.

Desai added that removing disparities that disproportionately prevent certain subgroups of patients from accessing SGLT2 inhibitors is necessary to fully realize the profound effects of SGLT2 inhibitors and drive value by reducing overall use of health care resources. To increase uptake of SGLT2 inhibitors in primary care practices, Turner commented, specialists should educate primary care physicians on their niche area (eg, kidney disease for a nephrologist) and updated data on the benefits of SGLT2 inhibitors.

Ganda added that the basis of the “metabolic memory” theory, which states that early treatment of hyperglycemia leads to better outcomes in type 2 diabetes and related complications, needs to be communicated to payers to improve coverage of SGLT2 inhibitors and other highly effective therapies. However, he is optimistic that widespread use of SGLT2 inhibitors eventually could have an effect on health outcomes similar to that of intensive statin therapy on blood lipid profiles.25

Desai concluded the section by stating that a reevaluation of quality measures is also important to reassess the meaning of quality care for patients. “This is an area where the interests of the patients, … providers, and … payers really can come together, and the use of high-value therapies could meaningfully improve the outcomes and lives [of] our patients and reap some financial benefits to the payers,” said Desai. “If we make it easy for the providers to write for these drugs and get access for the patients that they want, it is an instance where cardiorenal and cardiometabolic care could be at the very leading edge of what value-based care could look like, where the incentives are fully aligned.”

CLOSING REMARKS

At the end of the discussion, Turner said that SGLT2 inhibitors are “a gateway into better things to come,” and more drugs that have meaningful effects on patient outcomes and health are likely to come along in the near future. Similarly, Desai expressed excitement at the rapid pace of emerging evidence and changing guidelines, although he pointed out that such agents can only have a benefit if they reach the patients who need them. “It’s really a call to action for all of us to say, what do we do with all this data?” he said. “What do we do with all this evidence? And how do we sort of align our clinical practice with the evidence that we see accumulating out there?”

Ganda added that use of SGLT2 inhibitors now affords an effective way to treat diabetes and prevent complications and mortality. “We are now seeing, with these new drugs, effects on mortality, which [were] never seen before with any other drug,” he said.

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