National Trends in Use of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists by Cardiologists and Other Specialties, 2015 to 2020

Abstract

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) mitigate cardiovascular risk in individuals with type 2 diabetes, but most eligible patients do not receive them. We characterized temporal trends in SGLT2i and GLP-1RA use by cardiologists compared with other groups of clinicians. Methods and Results We conducted a descriptive analysis of serial, cross-sectional data derived from IQVIA's National Prescription Audit, a comprehensive audit capturing ≈90% of US retail prescription dispensing and projected to population-level data, to estimate monthly SGLT2is and GLP-1RAs dispensed from January 2015 to December 2020, stratified by prescriber specialty and molecule. We also used the American Medical Association's Physician Masterfile to calculate average annual SGLT2is and GLP-1RAs dispensed per physician. Between January 2015 and December 2020, a total of 63.2 million SGLT2i and 63.4 million GLP-1RA prescriptions were dispensed in the United States. Monthly prescriptions from cardiologists increased 12-fold for SGLT2is (from 2228 to 25 815) and 4-fold for GLP-1RAs (from 1927 to 6981). Nonetheless, cardiologists represented only 1.5% of SGLT2i prescriptions and 0.4% of GLP-1RA prescriptions in 2020, while total use was predominated by primary care physicians/internists (57% of 2020 SGLT2is and 52% of GLP-1RAs). Endocrinologists led in terms of prescriptions dispensed per physician in 2020 (272 SGLT2is and 405 GLP-1RAs). Cardiologists, but not noncardiologists, increasingly used SGLT2is over GLP-1RAs, with accelerated uptake of empagliflozin and dapagliflozin coinciding with their landmark cardiovascular outcomes trials and subsequent US Food and Drug Administration label expansions. Conclusions While use of SGLT2is and GLP-1RAs by cardiologists in the United States increased substantially over a 6-year period, cardiologists still account for a very small proportion of all use, contributing to marked undertreatment of individuals with type 2 diabetes at high cardiovascular risk.

Keywords: GLP‐1 receptor agonists; SGLT2 inhibitors; cardiometabolic health; prescribing patterns; risk reduction; type 2 diabetes.

Figure 1. Cardiologist contribution to use of SGLT2is and GLP‐1RAs.

SGLT2i (A) and GLP‐1RA (B) prescriptions by cardiologists. The primary axis in orange shows the percentage of overall monthly dispensed prescriptions for each drug class that are attributed to cardiologists; the secondary axis in blue shows the absolute number of dispensed prescriptions by cardiologists each month. While cardiologists have substantially increased absolute numbers of prescriptions, they continue to account for a very small proportion of overall use. GLP‐1RA indicates glucagon‐like peptide‐1 receptor agonists; and SGLT2i, sodium‐glucose cotransporter‐2 inhibitor. Source: IQVIA National Prescription Audit, 2015–2020.

Figure 2. SGLT2i and GLP‐1RA use across clinician specialties.

Monthly SGLT2i (A) and GLP‐1RA (B) dispensed prescriptions by specialty of the prescriber. PCP/internist prescribers accounted for the majority of dispensed prescriptions. Arrows delineate a subset of relevant clinical trial publications and key regulatory actions. APP indicates advanced practice provider; CREDENCE, Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation; CV, cardiovascular; DAPA‐HF, Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure; DECLARE‐TIMI, Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events; EMPA‐REG OUTCOME, BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; FDA, US Food and Drug Administration; GLP‐1RA, glucagon‐like peptide‐1 receptor agonists; HF, heart failure; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; PCP/Int Med, primary care physicians and internists; SGLT2i, sodium‐glucose cotransporter‐2 inhibitor; SQ, subcutaneous; and SUSTAIN‐6, Trial to Evaluate Cardiovascular and Other Long‐Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes 6. Source: IQVIA National Prescription Audit, 2015–2020.

Figure 3. Prescriptions per physician in 2020.

Estimated average SGLT2i and GLP1‐RA prescriptions dispensed per physician by specialty from January to December 2020. Endocrinologists outpace all other physician specialties in per‐physician use. GLP‐1RA indicates glucagon‐like peptide‐1 receptor agonists; PCP/Int Med primary care physicians and internists; and SGLT2i, sodium‐glucose cotransporter‐2 inhibitor. Source: IQVIA National Prescription Audit, 2015–2020.

Figure 4. Drug choice among cardiologists and noncardiologists.

Proportion of monthly SGLT2i/GLP‐1RA dispensed prescriptions from cardiologists (A) or noncardiology clinicians (B) attributed to each molecule in the 2 drug classes. Within each graph, SGLT2i drugs are shaded in blue hues, while GLP‐1RA drugs are shaded in brown hues. The gray series (other) corresponds to ertugliflozin and albiglutide, which each accounted for <1% of the total prescriptions. Arrows delineate a subset of relevant clinical trial publications and key regulatory actions. CV indicates cardiovascular; DAPA‐HF, Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure; EMPA‐REG OUTCOME, BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; EMPEROR‐Reduced, Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction; FDA, US Food and Drug Administration; GLP‐1RA, glucagon‐like peptide‐1 receptor agonists; HF, heart failure; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; PCP/Int Med, primary care physicians and internists; SGLT2i, sodium‐glucose cotransporter‐2 inhibitor; and SQ, subcutaneous. Source: IQVIA National Prescription Audit, 2015–2020.

Figure 5. Share of SGLT2i prescriptions comprised by dapagliflozin and empagliflozin.

Share of monthly SGLT2i dispensing attained by dapagliflozin (A) and empagliflozin (B) among cardiologists compared with all other clinicians. Arrows delineate a selection of landmark cardiovascular outcomes trial publications and key FDA indication expansions which may have influenced prescription choice among clinicians. CV indicates cardiovascular; DAPA‐HF, Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure; EMPA‐REG OUTCOME, BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; EMPEROR‐Reduced, Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction; FDA, US Food and Drug Administration; GLP‐1RA, glucagon‐like peptide‐1 receptor agonists; HF, heart failure; and SGLT2i, sodium‐glucose cotransporter‐2 inhibitor. Source: IQVIA National Prescription Audit, 2015–2020.

Figure 6. Prescriptions of daily vs weekly injection GLP‐1RAs.

Since January 2015, the absolute number of dispensed prescriptions for daily injection GLP‐1RAs has stagnated, while weekly injection GLP‐1RA prescriptions have increased substantially, accounting for the majority of GLP‐1RA prescriptions in 2020 (A). This shift from daily to weekly GLP‐1RA injections is also reflected in each category’s relative proportion of GLP‐1RA prescriptions (B). Daily injection GLP‐1RAs are lixisenatide, liraglutide, and short‐acting exenatide (Byetta). Weekly injections are albiglutide, dulaglutide, subcutaneous semaglutide, and long‐acting exenatides (Bydureon, Bydurean BCise, and Bydureon Pen). CV indicates cardiovascular; FDA, US Food and Drug Administration; GLP‐1RA, glucagon‐like peptide‐1 receptor agonists; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; REWIND, Researching Cardiovascular Events With a Weekly Incretin in Diabetes; SGLT2i, sodium‐glucose cotransporter‐2 inhibitor; SQ, subcutaneous; and SUSTAIN‐6, Trial to Evaluate Cardiovascular and Other Long‐Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes 6. Source: IQVIA National Prescription Audit, 2015–2020.