There is a "striking" discordance between evidence-based, guideline-recommended use of sodium-glucose cotransporter–2 (SGLT2) inhibitors for the treatment of type 2 diabetes "and their actual uptake in clinical practice," say the authors of a new study.
The research, based on pharmacy claims from a national database made during the first years after the US Food and Drug Administration (FDA) approved this class of agents, was published online in Diabetes Technology and Therapeutics.
Rozalina G. McCoy, MD, Department of Medicine, Mayo Clinic, Rochester, Minnesota, and colleagues investigated the period after the FDA approved canagliflozin (March 2013), dapagliflozin (January 2014), and empagliflozin (August 2014), when guidelines recommended the use of these agents as second-line therapy after metformin, especially for patients at risk for hypoglycemia.
Disparities in Prescribing
The researchers wanted to see which patients were being prescribed these agents before the cardiovascular outcome trials "muddied the waters" by reporting that these agents provided cardiovascular and renal protection, McCoy told Medscape Medical News.
"Early on, it was apparent that [SGLT2 inhibitors] are not associated with weight gain or hypoglycemia but can lower blood pressure and weight, thereby making them particularly attractive treatment options for overweight or obese patients, patients with comorbid heart failure or hypertension, patients at risk for hypoglycemia, and the elderly," the authors report.
However, in the current study, paradoxically, patients with cardiovascular disease, heart failure, hypertension, chronic kidney disease, and those at risk for hypoglycemia were less likely to receive an SGLT2 inhibitor compared to other patients.
In addition, patients who were black, female, older, or who were covered by Medicare Advantage insurance were less likely to receive these newer drugs than patients who were white, younger, male, or privately insured.
McCoy speculates that physicians may be reluctant to prescribe a new drug if they don't have experience using it to treat frail patients who have many comorbidities.
"I think it is very important to be cautious with our frail patients," she said, "but at the same time, we don't want to deprive them of clinically preferred treatment."
According to McCoy, clinicians need to "use best clinical judgement...and think about what is the medication that the patient in front of me would really benefit from the most."
"We Need to Bridge This Chasm"
Speaking at the recent European Association for the Study of Diabetes (EASD) 2019 meeting, where she discussed the findings of the McCoy study, Melanie Davies said: "The challenge we have…is that SGLT2 inhibitors are currently underprescribed, and when they are prescribed, they're being prescribed to the patients who are not likely to benefit the most."
Davies is professor of diabetes medicine at the University of Leicester, United Kingdom.
"We need to bridge this chasm between the reality in present and where the evidence suggests we should be," she told meeting delegates.
"If you had prior myocardial infarction, or heart failure, or chronic kidney disease," Davies noted, referring to the patients in the McCoy study, "you were even less likely to be prescribed these [newer] agents."
A Look Back at Early Adopters
For their study, McCoy and colleagues identified 1,054,727 adults with type 1 or type 2 diabetes who had private or Medicare Advantage health insurance in a large, US health insurance plan and had filled at least one prescription for at least one glucose-lowering medication between January 1, 2013, and December 31, 2016.
Of these, 75,500 patients (7.2%) filled a first prescription for an SGLT2 inhibitor (canagliflozin, dapagliflozin, empagliflozin). Most patients (70%) received canagliflozin.
The researchers note that even during the period they studied, SGLT2 inhibitors were recommended ― in May 2013 by AACE/ACE as third-line agents, as second-line agents in 2014–2015 by various organizations, and in January 2016, based on the EMPA-REG trial. Their use was recommended for patients with heart failure and cardiovascular disease.
The researchers found that 2.3% of the patients who were prescribed SGLT2 inhibitors in 2014 had type 1 diabetes, despite this use being off label.
The percentage dropped to 1.2% in 2016 — in parallel with growing awareness of increased risk for ketoacidosis with use of these agents in patients with type 1 diabetes who were receiving insulin.
Did It Take Time for Information to Trickle Down to Generalists?
During the study years, most SGLT2 inhibitors were prescribed by primary care clinicians (32% family medicine, 24% internal medicine); 23% were prescribed by endocrinologists.
Despite evidence supporting the preferential use of an SGLT2 inhibitor for patients with certain comorbidities, the authors write, clinical practice did not reflect this.
Patients with diabetes and prior myocardial infarction, heart failure, kidney disease, or severe hypoglycemia were 6%, 7%, 20%, and 4% less likely, respectively, to be prescribed this type of drug (P < .001 for all).
There were also differences in prescribing with respect to patient demographics and insurance coverage.
Compared with diabetes patients who were aged 18 to 44 years, those who were aged 75 years or older were 43% less likely to receive an SGLT2 inhibitor (P < .001).
Compared with patients who had commercial insurance, those with Medicare Advantage were 36% less likely to receive this class of drug (P < .001).
Patients who received SGLT2 inhibitors were also more likely to be male than female (49% vs 45%).
Black patients were 7% less likely than white patients to receive an SGLT2 inhibitor.
"Patients with myocardial infarction, heart failure, and prior hypoglycemia were less likely to use SGLT2 inhibitors despite evidence supporting their preferential use in these patients," the authors reiterate.
The drugs "were initiated most often by lowest-risk patients (ie, young, with fewer comorbidities), without the health conditions most likely to benefit," the authors state.
There were also "apparent racial/ethnic, regional, and insurance‐based disparities in use," they observe.
However, over the course of the study, they did find that the proportion of patients aged 65 or older who received an SGLT2 inhibitor increased from 12% to 28%, as did the proportion who had Medicare Advantage insurance, from 14% to 32% (P < .001 for both).
The authors speculate that clinicians, especially generalists, may have initially been unaware of emerging class-specific benefits of SGLT2 inhibitors, so they may have prescribed these new, costly agents to younger patients and those with less comorbidities who they believed warranted a more intensive approach to therapy.
Younger patients may have also been more likely to ask for new medication as a result of direct‐to‐consumer advertising.
Although SGLT2 inhibitors were on the formularies, people with Medicare Advantage may not have been able to afford brand name medications, because such patients are not eligible for the same discount programs as people with commercial insurance.
Think About Absolute Benefits in Individual Patients
Davies said: "The current consensus...advocates that we should be using these therapies in around a quarter to a half [of patients with diabetes]."
However, she stressed that "we should be thinking about the absolute benefit" of these drugs in "the patients we're targeting."
She noted that the large outcomes trials with SGLT2 inhibitors have found major differences in the number needed to treat (NNT) with these agents to provide benefits with respect to major adverse cardiac events, including heart failure, and more recently, renal outcomes.
For example, in the DECLARE TIMI-HF study, there was a 10-fold variation in the NNT to gain benefits from dapagliflozin, she noted. In patients at highest risk, the NNT was only 36, but for those at lowest risk, it was 303.
So the "drive to treat all of our diabetes patients with SGLT2 inhibitors [and GLP1 agonists], I would argue, is a little premature," she concluded.
The authors agree and say that this study highlights the importance of individualized treatment.
"Patient and clinician education regarding individualized approaches to diabetes management, and health plan support of such evidence‐based treatment strategies, may therefore help improve access to new diabetes therapeutics and improve health outcomes among patients living with this disease," they conclude.
Diabetes Technol Ther. Published online October 9, 2019. Abstract
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Cite this: Newer Diabetes Drugs Given to Those Who Need Them Least - Medscape - Oct 24, 2019.
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