Miriam E. Tucker
February 26, 2020
Between 2013 and 2018, empagliflozin and dulaglutide became the most-prescribed drugs in their respective classes for treating type 2 diabetes in the United States, new research shows.
The findings, from US-based administrative claims data, were published online February 10 in Diabetes Care by Chintan V. Dave, PharmD, PhD, and colleagues.
Among patients initiating oral sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) over the 5-year period, empagliflozin (Jardiance, Boehringer Ingelheim/Lilly) became the most commonly prescribed glucose-lowering drug, primarily driven by an increasing proportion of patients with diabetes who had a diagnosis of myocardial infarction, stroke, or heart failure (collectively called cardiovascular disease-heart failure [CVD-HF]).
And within the SC injectable glucagon-like peptide 1 receptor (GLP-1) agonist class, initiations of dulaglutide (Trulicity, Lilly) surpassed liraglutide in 2013-2018, although those starting liraglutide (Victoza, Novo Nordisk) were more likely to have a CVD-HF diagnosis.
"This study shows that by preferring empagliflozin, prescribers have largely reacted in accordance with the available evidence and drug labels, while other factors such as lower price, frequency of administration [dulaglutide is given weekly and liraglutide is given daily], or prior authorizations may have led prescribers to select dulaglutide over liraglutide," Dave, of the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, and colleagues write.
Internists and endocrinologists were the most frequent prescribers of both drug classes.
Cardiologists rarely prescribed them, even for patients with established CVD-HF.
"As patients with co-occurring diabetes and CVD are likely to see their cardiologist, these encounters may provide an additional opportunity to optimize their treatment," the authors emphasize.
For SGLT2 inhibitors, Label Changes a Likely Contributor
Over the study period, the proportion of patients who had CVD-HF receiving SGLT2 inhibitors rose by 3.4% (P trend<.001).
The proportion of overall prescriptions for SGLT2 inhibitors written by endocrinologists dropped by 12.0%, although the absolute number of SGLT2-inhibitor prescriptions written by endocrinologists increased (P<.001).
The proportion written by internists didn't change (P=.58), while it increased slightly among cardiologists but still barely exceeded 1% (P<.001). The findings were similar for the subgroup of patients with CVD-HF who initiated SGLT2 inhibitors.
By individual agents, canagliflozin (Invokana, Janssen) prescriptions dropped by 75.1% over the study period, from 100% in 2013 to just 24.9% by 2018 (P<.001), while empagliflozin initiation rose by 51.7%, from 13.9% to 65.6% of all SGLT2 inhibitor initiations (P<.001).
Among those initiating empagliflozin, the proportion with CVD-HF rose by 5.3% (P<.001), mostly after the additional indication for reducing CV events and death was added to the US label in December 2016.
In contrast, there were no significant changes in the proportions of those with CVD-HF who initiated canagliflozin (P=.065), dapagliflozin (P=.87), or other medications (P=.060).
"Changes in the drug label for canagliflozin (boxed warning for amputation) and empagliflozin (for reduction in CV events and death) in 2016 likely contributed to a rapid change in prescribing preference for empagliflozin," Dave and colleagues write.
With GLP-1 Agonists, Perhaps Frequency of Administration Matters
Among those starting GLP-1 agonists, the proportion with CVD-HF increased by 3.9% (P<.001) during the study period.
Prescriptions by endocrinologists declined as a proportion, but rose in absolute numbers (P<.001), and remained consistent for internists (>55%; P=.12).
Prescribing of GLP-1 agonists by cardiologists remained low (<0.5%) and was not higher for individuals with CVD-HF.
By individual GLP-1 agonist, liraglutide initiation declined by 32.1%, from 72.4% to 40.3% of GLP-1 agonist initiations (P<.001) whereas dulaglutide initiation rose by 43.8%, from 5.0% to 48.8% (P<.001). Again, these trends were similar in the subgroup of patients with CVD-HF.
The proportion of patients with CVD-HF among liraglutide initiators increased by 5.1%, from 10.5% to 15.6% (P=.018), and among exenatide initiators by 2.1%, from 10.3% to 13.8% (P=.77).
"Due to the reduced frequency of administration and possible formulary preferences, dulaglutide initiations surpassed liraglutide, the only GLP-1 agonist with evidence of CV benefit at the time," Dave and colleagues note.
Dulaglutide has just been granted an additional approval by the US FDA for reducing the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes with and without established CVD or multiple CV risk factors.
This makes it the first and only type 2 diabetes medicine approved to reduce the risk of CV events for both primary and secondary prevention populations.
The study was funded by the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Dave has reported receiving support from the New Jersey Alliance for Clinical and Translational Science.
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