Trends in prescribing sodium‐glucose cotransporter 2 inhibitors for individuals with type 2 diabetes with and without cardiovascular‐renal disease in South Korea, 2015–2021

ABSTRACT

Background

This study evaluates shifts in oral glucose‐lowering drug prescription patterns and the adoption of sodium‐glucose cotransporter 2 inhibitors (SGLT2is) in South Korea.

Methods

A cross‐sectional and retrospective cohort analysis of the Korean National Health Insurance database (2015–2021) assessed the prescription patterns of oral glucose‐lowering drugs by therapy level, SGLT2i prescriptions by cardiovascular‐renal disease (CVRD) status, and the mean duration for SGLT2i therapy initiation and intensification.

Results

From 2015 to 2021, the number of individuals prescribed oral glucose‐lowering drugs across all regimen levels increased. However, the proportion of individuals receiving monotherapy or dual combination therapy decreased by 9.2 percentage points, whereas the proportion prescribed triple or more combination therapy increased. SGLT2i prescriptions increased from 2.5% in 2015 to 13.9% in 2021, marking an 11.4 percentage point growth. This trend was consistent among individuals with and without CVRD, with the most significant increase observed in individuals with heart failure—from 2.2% in 2015 to 16.6%. The mean time to SGLT2i initiation post‐diagnosis was shortened from 249 days in 2015 to 158 days in 2019.

Conclusions

The adoption of SGLT2i therapy was on the rise, especially among individuals with heart failure, accompanied by a notable decrease in time to treatment initiation. Despite these positive trends, the overall use of SGLT2i among individuals with CVRD remained limited.

This study evaluates shifts in oral glucose‐lowering drug prescription patterns and the adoption of sodium‐glucose cotransporter 2 inhibitors (SGLT2is) in South Korea from 2015 to 2021. The findings indicate a significant increase in SGLT2i use, particularly among individuals with heart failure; however, overall utilization remained limited among those with cardiovascular‐renal disease.

INTRODUCTION

The incidence of adverse cardiovascular‐renal events is significantly higher in individuals with diabetes compared to those without diabetes ¹ , ² . Moreover, in South Korea, the aging population has led to an increase in the prevalence of older adults with diabetes, highlighting a growing public health concern ³ . This demographic shift indicates that individuals with diabetes are more likely to have multiple comorbidities, thereby elevating their risk for cardiovascular‐renal complications ⁴ . Given these challenges in clinical practice, it is imperative that management of diabetes is expanded beyond glucose control to include a comprehensive strategy aimed at reducing cardiorenal risk.

Recent meta‐analysis from clinical trials have demonstrated that sodium‐glucose cotransporter 2 inhibitors (SGLT2is) are associated with a 14% reduction in cardiovascular death, a 12% reduction in major adverse cardiovascular events (MACEs), a 30% reduction in hospitalization for heart failure (HHF), and a 35% reduction in composite renal outcomes ⁵ . The 2019 update of the joint consensus report by the American Diabetes Association and the European Association for the Study of Diabetes introduced two significant changes related to the use of SGLT2i for the first time: First, it is recommended to consider treating high‐risk individuals with either a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) or an SGLT2i to reduce MACE, HHF, cardiovascular death, or chronic kidney disease (CKD) progression. Second, for individuals with type 2 diabetes and heart failure, particularly those with a reduced ejection fraction, SGLT2is are advised to decrease the risk of HHF, MACE, and cardiovascular death. This recommendation also extends to individuals with type 2 diabetes and CKD to prevent the progression of CKD, HHF, MACE, and cardiovascular death ⁶ . These changes were sustained in the 2022 joint consensus report produced by the American Diabetes Association and the European Association for the Study of Diabetes ⁷ . In line with these updates, the 2021 guidelines of the Korean Diabetes Association also recommended considering SGLT2is for individuals with type 2 diabetes and heart failure, atherosclerotic cardiovascular disease (ASCVD), or CKD ⁸ . These recommendations were maintained in the 2023 guidelines ⁹ .

Despite these recommendations, there is still a lack of data on the actual patterns of SGLT2i prescription and uptake among individuals with type 2 diabetes, differentiated by the presence or absence of cardiovascular‐renal disease (CVRD). Therefore, we investigated the treatment patterns of SGLT2i among individuals with type 2 diabetes based on their CVRD status using the Korean National Health Insurance Service (NHIS) database from 2015 to 2021.

MATERIALS AND METHODS

Data source and study population

South Korea operates a mandatory, single‐payer national healthcare insurance system, encompassing approximately 98% of the Korean population. The Korean NHIS database contains comprehensive data, including sociodemographic characteristics, reimbursement claims—specified by the International Classification of Diseases, 10th Revision (ICD‐10) codes, and Anatomical Therapeutic Chemical (ATC) codes—as well as mortality records ¹⁰ .

We identified individuals aged ≥19 years with type 2 diabetes, defined by the diagnosis of diabetes (ICD‐10 codes E11–E14) and concurrent prescription of oral glucose‐lowering drugs (ATC codes A10B), from January 1, 2015, to December 31, 2021. From this population, we excluded individuals diagnosed with type 1 diabetes (ICD‐10 code E10) or cancer (ICD‐10 codes C00–C97) from January 1, 2014, to December 31, 2021. Within the data, we focused on two datasets with distinct objectives: (1) to examine the trend in prescription patterns in a cross‐sectional study and (2) to assess the meantime to SGLT2i initiation over a 2‐year follow‐up period in a retrospective cohort study. The study protocol was approved by the Institutional Review Board of Ajou University Hospital, Suwon, Republic of Korea (approval no. AJOUIRB‐EXP‐2022‐355), and the requirement for informed consent was waived.

Prescription patterns by CVRD status

The trend in prescription patterns of oral glucose‐lowering drugs among individuals with type 2 diabetes was assessed from the year of type 2 diabetes diagnosis until the earliest of (1) death, (2) initiation of injectable therapies, or (3) the end of the study period (December 31, 2021). Prescription patterns were evaluated on an annual basis. For example, if injectable therapies were started in August 2019 after the diagnosis in 2015, prescription patterns for 2016 were analyzed using prescriptions from January 1, 2016, to December 31, 2016, whereas patterns for 2019 were assessed from January 1, 2019, to July 31, 2019. The therapy regimen level (i.e., mono‐, dual‐, triple‐, ≥quadruple without SGLT2i, and ≥quadruple with SGLT2i therapy) was determined based on glucose‐lowering drug classifications (Table S1). Individuals who were prescribed oral glucose‐lowering drugs in a previous year but were not prescribed them in subsequent years were categorized as non‐users.

CVRD was defined as a composite of ASCVD, heart failure (HF), and CKD. ASCVD was identified by at least one claim (outpatient or inpatient) with ICD‐10 codes I20–I25 or I60–I64, designated as either the principal diagnosis or within the first four additional diagnoses, or it was confirmed through procedures related to ASCVD. Similarly, HF and CKD were identified by at least one claim (outpatient or inpatient) with their respective ICD‐10 codes, I50 for HF and N18 for CKD, as the principal diagnosis or among the first four additional diagnoses. The status of CVRD was determined based on diagnoses from January 1, 2014, to December 31, 2021. For example, when evaluating the prescription patterns for 2016, CVRD status was ascertained from January 1, 2014, to December 31, 2016.

Time to SGLT2i initiation and intensification

Between 2015 and 2019, we conducted analyses on three datasets to evaluate the mean time to initiation of SGLT2is by stage of treatment intensification. Initially, we identified individuals with newly diagnosed type 2 diabetes (N = 1,239,854). Subsequently, we categorized individuals who initiated monotherapy (N = 587,165) and those who commenced dual combination therapy (N = 19,480). For each cohort, follow‐up for the initiation of SGLT2is began on the respective dates of type 2 diabetes diagnosis, monotherapy initiation, and dual combination therapy initiation, and concluded at the date of SGLT2i initiation, within a 2‐year follow‐up period.

Statistical analysis

Prescription patterns from 2015 to 2021 were analyzed and classified into categories: non‐user, monotherapy, dual combination therapy, triple combination therapy, ≥quadruple combination therapy without SGLT2is, and ≥quadruple combination therapy with SGLT2is, based on the annual prescription data for each individual. When an individual received more than one pattern within a year, each pattern was recorded separately. Additionally, the top 10 treatment patterns in 2021 were identified and compared with the number of prescriptions for individuals in 2015. The annual proportion of individuals prescribed SGLT2i according to CVRD status was determined by dividing the number of individuals who received an SGLT2i prescription by the total number of individuals diagnosed with diabetes in that specific year. Additionally, the mean time to initiation and intensification of SGLT2i therapy, segmented by stage of treatment intensification, was determined and comparisons were made between the years 2015 and 2019. All analyses were performed using SAS Enterprise Guide 7.1 (SAS Institute, Cary, NC, USA).

RESULTS

The number of individuals with type 2 diabetes prescribed oral glucose‐lowering drugs increased, from 1,847,901 in 2015 to 3,259,667 in 2021. During the same period, both the mean age and the proportion of male individuals experienced an upward trend. Additionally, the proportion of individuals with CVRD increased from 26.2% to 37.6%, as detailed in Table S2.

Overall prescription patterns by therapy regimen level

During the study period, there was an observed increase in the number of individuals prescribed therapy at all regimen levels, as shown in Figure 1. Overall, the number of individuals prescribed oral glucose‐lowering drugs increased from 2,304,000 in 2015 to 3,578,000 in 2021. Some individuals may be counted more than once if they transitioned between different types of therapy during this period. Therefore, the number differs from that in Table S2. By therapy regimen levels, monotherapy prescriptions increased from 726,000 in 2015 to 980,000 in 2021. Dual combination therapy prescriptions increased from 1,029,000 to 1,515,000, and triple combination therapy from 530,000 to 1,031,000. Quadruple combination therapy without SGLT2i increased from 17,000 to 37,000, and with SGLT2i from 2,000 to 15,000. Despite this overall rise, the proportion of individuals on monotherapy or dual combination therapy declined by 9.2 percentage points (from 39.3% in 2015 to 30.1% in 2021 for monotherapy, and from 55.7% in 2015 to 46.5% in 2021 for dual combination therapy). In contrast, the proportion of individuals receiving triple or more combination therapy increased (from 28.7% in 2015 to 31.6% in 2021 for triple combination therapy; from 0.9% in 2015 to 1.1% in 2021 for ≥quadruple combination therapy without SGLT2is; and from 0.1% in 2015 to 0.5% in 2021 for ≥quadruple combination therapy with SGLT2is). Remarkably, the proportion of individuals not prescribed any glucose‐lowering drugs increased by 4.7 percentage points (from 4.2% in 2016 to 8.9% in 2021), as depicted in Figure S1.

Figure 1.

Number of individuals prescribed oral glucose‐lowering drugs by levels of therapy regimen. SGLT2i, sodium‐glucose cotransporter 2 inhibitor.

The top 10 most prescribed oral glucose‐lowering drugs in 2021 are presented in Figure 2. The combination of metformin with a dipeptidyl peptidase 4 inhibitor (DPP‐4i) was the most commonly prescribed therapy, followed by metformin monotherapy, and a triple regimen of metformin, DPP‐4i, and sulfonylurea (SU). This hierarchy was consistent among individuals, regardless of CVRD status. The combination of metformin with SGLT2i and the triple combination therapy including metformin, SGLT2i, and SU was ranked fourth and sixth, respectively. Notably, there has been a significant increase in the number of individuals prescribed these regimens since 2015, for both groups with and without CVRD.

Figure 2.

Top 10 most prescribed oral glucose‐lowering drugs in 2015 and 2021. CVRD, cardiovascular‐renal disease; DPP‐4i, dipeptidyl peptidase 4 inhibitor; MET, metformin; SGLT2i, sodium‐glucose cotransporter 2 inhibitor; SU, sulfonylurea; TZD, thiazolidinediones.

Prescription of SGLT2i by CVRD status

The number of individuals prescribed SGLT2i increased from 46,000 in 2015 to 448,000 in 2021. Concurrently, the proportion of individuals prescribed SGLT2is increased from 2.5% in 2015 to 13.9% in 2021, an increase of 11.4 percentage points. The most significant increase was observed in the triple regimen, which experienced a 17.8 percentage point increase (Figure S2). This increase was consistent among individuals with CVRD (an 11.8 percentage point increase) and those without CVRD (an 11.2 percentage point increase). Furthermore, the trend of increasing prescriptions persisted across all categories of ASCVD, HF, and CKD, with the most notable increase observed in individuals with HF—from 2.2% in 2015 to 16.6% in 2021, a 14.4 percentage point increase (Figure 3).

Figure 3.

Trends in the proportion of individuals prescribed sodium‐glucose cotransporter 2 inhibitor by cardiovascular‐renal disease status. ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease; CVRD, cardiovascular‐renal disease; HF, heart failure.

Time to initiation and intensification of SGLT2i

The mean duration to initiate SGLT2i therapy following a diagnosis of type 2 diabetes decreased from 249 days in 2015 to 158 days in 2019. During this period, the time to SGLT2i initiation after diagnosis was reduced to 45 days for monotherapy (from 193 days in 2015 to 148 days in 2019) and 79 days for dual combination therapy (from 249 days in 2015 to 170 days in 2019). For individuals on monotherapy, the time to intensify treatment with dual combination therapy with SGLT2i was shortened by 30 days (from 360 days in 2015 to 330 days in 2019). However, the transition period from dual to triple combination therapy lengthened by 26 days (from 288 days in 2015 to 314 days in 2019; Figure 4).

Figure 4.

Time to initiation and intensification of sodium‐glucose cotransporter 2 inhibitor. SGLT2i, sodium‐glucose cotransporter 2 inhibitor.

DISCUSSION

In a nationwide database study of individuals with type 2 diabetes, we observed an increase in the number of individuals prescribed oral glucose‐lowering drugs across all treatment regimen levels. However, there was a trend toward a higher proportion of individuals being prescribed triple or more combination therapy, while the proportion receiving monotherapy or dual combination therapy declined. According to the Korea National Health and Nutrition Examination Survey (KNHANES), the estimated diabetes population in South Korea increased from 3.21 million in 2015 to 5.60 million in 2021, marking a 1.7‐fold increase, driven by improvements in diabetes management and extended lifespans ¹¹ , ¹² . The treatment rate for individuals with diabetes also rose from 56.7% in 2015 to 61.4% in 2021, corresponding to an increase from 1.82 million treated patients in 2015 to 3.44 million in 2021 ¹¹ , ¹³ . Additionally, the proportion of individuals with diagnosed diabetes not receiving pharmacological treatment decreased by more than half, from 10.9% in 2013–2014 to 5.0% in 2021–2022 ¹¹ , ¹⁴ . This decrease likely reflects the adoption of more aggressive treatment strategies and earlier intervention, emphasizing the importance of early diabetes management. According to the 2022 Diabetes Fact Sheet by the Korean Diabetes Association, in South Korea, the number of individuals prescribed glucose‐lowering drugs increased from 929,119 in 2002 to 3,900,596 in 2019. During this period, the proportion of individuals prescribed triple or more combination therapy increased, whereas prescriptions for monotherapy and dual combination therapy declined ⁴ . The trend towards an increasing treatment rate and more intensive therapy may be attributed to the recent development of several oral antidiabetic agents with improved safety profiles, which has led to a more proactive adoption of combination therapies to optimize glycemic control. Additionally, the progressive expansion of insurance reimbursement for combination therapies in South Korea has further facilitated their use in clinical practice. Moreover, individuals with diabetes often have multiple comorbidities, such as hypertension and hypercholesterolemia, which underscore the necessity for therapy intensification and the adoption of new pharmacological treatments. Between 2013–2014 and 2021–2022, the prevalence of hypertension among individuals with diabetes increased from 54.7% to 59.6%, while the prevalence of hypercholesterolemia rose significantly from 31.6% to 74.2% during the same period ¹¹ , ¹⁴ . In particular, the prevalence of diabetes among older adults increased from 25.9% in 2011 to 29.4% in 2022 ³ . Approximately 50% of older adults in South Korea also have hypertension, dyslipidemia, and obesity ¹⁵ . This rise in comorbidities is expected to continue due to the aging diabetic population, likely leading to a higher demand for triple or more combination therapies. The shift towards more intensive treatment not only reflects adherence to guidelines but also highlights a growing number of individuals with poor glycemic control or a long duration of diabetes. The proportion of individuals with diabetes achieving a glycated hemoglobin (HbA_1c) level of <6.5% decreased from 28.3% during 2016–2018 to 24.5% in 2019–2020 ¹⁶ , ¹⁷ . Moreover, the increasing prevalence of microvascular complications further indicates an increase in individuals with poor glycemic control ¹⁸ .

The current study showed that 4.2% had discontinued treatment by 2016, rising to 8.9% in 2021, marking a 4.7 percentage point increase. In the KNHANES, 6.5% of individuals diagnosed with diabetes in 2019–2020 were not prescribed glucose‐lowering medications ¹⁶ . A recent study of over 80,000 privately insured US adults with type 2 diabetes who initiated second‐line glucose‐lowering drugs showed that nearly two‐thirds of individuals modified their treatment within 1 year of their initial prescription, with discontinuation being the most common modification (38.6%) ¹⁹ . Previous studies suggested several reasons for treatment discontinuation, such as concerns about medication efficacy, fear of hypoglycemia, the complexity of multi‐drug regimens, high cost, and insufficient diabetes knowledge ²⁰ . In South Korea, the incidence of diagnosed diabetes among young adults has been rising, a trend that may be partially influenced by the increased participation in national health screening programs ³ . As a result, there are cases where pharmacological treatment is initiated at an early stage, followed by a transition to non‐pharmacological management. This shift in treatment approach may contribute to the observed increase in treatment discontinuation rates.

In South Korea, DPP‐4is are widely used in both dual and triple therapy for type 2 diabetes, regardless of the presence of CVRD. Consistent with these findings, previous study showed that DPP‐4i is more commonly prescribed than SGLT2i or GLP‐1RA ²¹ . Individuals with ASCVD or high cardiovascular risk were about three times more likely to be prescribed DPP‐4i compared to SGLT2i or GLP‐1RA ²² , ²³ . Additionally, a study in primary care conducted between 2013 and 2016 found that 23% of over 250,000 US individuals with type 2 diabetes were prescribed DPP‐4i as a second‐line therapy to metformin, compared to only 4% for SGLT2i and 6% for GLP‐1RA ²⁴ . In Denmark, DPP‐4i accounted for 5% of all antidiabetic agents prescribed in 2017, with the proportion of new initiators remaining stable since 2014 ²⁵ , ²⁶ . Several factors drive the widespread use of DPP‐4is. First, they effectively reduce HbA1c levels by 0.5–1.0% and have a low risk of hypoglycemia, making them particularly suitable for individuals with moderate to advanced CKD or for older adults. Second, DPP‐4is are known for their good tolerability, ease of administration, and weight‐neutral effect, distinguishing them from other glucose‐lowering agents, such as sulfonylureas or insulin, which carry higher risks of weight gain and hypoglycemia. Third, large clinical trials have demonstrated the cardiovascular safety of DPP‐4is, although caution is needed with certain agents like saxagliptin, due to potential heart failure risks ²⁷ . Furthermore, DPP‐4is showed better glucose‐lowering efficacy in Asian populations compared to other ethnic groups, which may be attributed to variations in body mass index influencing the HbA1c‐lowering response ²⁸ . Furthermore, in South Korea, the availability of nine distinct DPP‐4is may have contributed to their increased accessibility and convenience for physicians, making them a more favorable option compared to other antidiabetic medications.

In a meta‐analysis of the SGLT2i trial including six landmark trials, SGLT2is were associated with a reduced risk of MACE, HHF, and kidney outcomes ²⁹ . Furthermore, in trials with a focus on HF and kidney outcomes that allowed the inclusion of participants without diabetes, the efficacy of SGLT2is in reducing CVRD risks has been observed regardless of diabetes status and baseline glycemic control ³⁰ . Based on this evidence, the American Diabetes Association has expanded its guidelines to recommend SGLT2i for individuals with diabetes who have a high cardiovascular risk, HF, or CKD, regardless of their HbA1c levels and personalized glycemic targets ³⁰ , ³¹ . Consequently, the use of SGLT2i is now recognized as a goal in its own right, rather than merely a means to achieve glycemic control. In South Korea, SGLT2is have been approved for the treatment of type 2 diabetes since the end of 2013 and have been reimbursed since 2014. Since 2021, the Clinical Practice Guidelines issued by the Korean Diabetes Association have recommend prescribing SGLT2is to individuals with HF, ASCVD, and CKD ⁸ , ⁹ . Despite evidence from landmark trials demonstrating cardiorenal benefits among individuals with type 2 diabetes and guidelines recommendations, the rate of SGLT2i prescriptions remained low, even though the proportion of individuals prescribed SGLT2is increased from 2.5% in 2015 to 13.9% in 2021. Along with the increase in triple combination therapy prescriptions, there was also a rise in the prescription of triple combination therapy including SGLT2i. However, this increase was smaller compared to the rise in other triple combination therapies (data not shown). Furthermore, the proportion of individuals with CVRD who were prescribed SGLT2is was similar to those without CVRD (14.1% vs 13.8%), and even individuals with HF had a low prescription rate of SGLT2is (16.6%). In individuals with HF, the proportion of those prescribed SGLT2i was higher in secondary or tertiary hospitals than in primary care clinics (20.7% vs 13.3%, data not shown). These findings are consistent with prior studies. A previous study in South Korea demonstrated that the initiation of SGLT2i following cardiovascular events in 2019 was approximately 13% ²¹ . A multicenter retrospective cohort study conducted across 13 secondary or tertiary hospitals revealed that only approximately 25% of individuals received prescriptions for SGLT2is after experiencing cardiovascular events ³² .

The low prescription rate of SGLT2i in South Korea can be understood from two key perspectives. SGLT2i trials included less than 25% Asian participants, and due to the unique characteristics of diabetes in Asians, such as impaired β‐cell function, increased visceral obesity risk, and early‐onset diabetes, there are limitations in generalizing the trial results to this population ³³ . Furthermore, stroke constitutes a significant proportion of CVD cases among individuals with diabetes in Asians, which differs from other parts of the world. In South Korea, in 2015, the hospitalization rate for stroke in adults with diabetes was 257 per 10,000, significantly higher than for myocardial infarction (71 per 10,000) and heart failure (154 per 10,000) ³⁴ . Despite these higher stroke rates, the efficacy of SGLT2i in reducing stroke risk remains inconclusive based on current RCTs. This suggests that many of the ASCVD patients included in the current study may have primarily been stroke patients, which may have contributed to the relatively low use of SGLT2is. Furthermore, in the 2021 guidelines of the Korean Diabetes Association, the threshold for prescribing SGLT2is in individuals with an eGFR below 60 mL/min/1.73 m² was revised to 30 mL/min/1.73 m^{2 8} . This change likely contributed to the initially low prescription rates of SGLT2is in CKD patients. Therapeutic inertia may also contribute to the low prescription rates for SGLT2i. It represents a failure to escalate or de‐escalate medical therapy when clinically appropriate, influenced by factors related to clinicians, patients, and the healthcare system ³⁵ . From a clinician's perspective, several factors interrupted the prescription of SGLT2is. Time constraints during consultations, particularly when managing type 2 diabetes in conjunction with various other medical conditions, may restrict the opportunity for comprehensive treatment discussions. A lack of resources and inadequate training on treatment expansion may also be significant barriers to the adoption of new treatment guidelines ³⁵ , ³⁶ . Specifically, in South Korea, the complex and restrictive reimbursement criteria for SGLT2is may further contribute significantly to clinicians' hesitation in prescribing these medications (Table S3). Concerns regarding patient discomfort due to potential adverse effects, such as sudden weight loss, frequent urination, risk of genital infections, higher costs due to a restricted reimbursement scheme, and initial declines in renal function, also deter clinicians from SGLT2i prescriptions. Furthermore, in meta‐analysis of trials, SGLT2i were associated with an increased risk of genital infection and amputations ³⁷ . However, SGLT2i trials have generally reported similar or no increased adverse event rates with SGLT2is compared to controls among Asian populations, with incidence rates being relatively lower in Asians than in other regions ³³ . The exclusion of older adults from most trials further complicates the prescription of SGLT2is for this demographic. However, in South Korea, the initiation of SGLT2i therapy in individuals aged 65 and older did not lead to an increased risk of diabetic ketoacidosis, fractures, or severe hypoglycemia in real‐world settings ³⁸ . A recent study suggested tailored treatment for older adults with diabetes to maximize the benefits of SGLT2is while minimizing potential risks ³⁹ . Moreover, the increase in SGLT2i prescriptions might be attributed to the accumulating experience with SGLT2i prescriptions, reducing concerns about adverse events. However, the overall prescription rate of SGLT2is continued to be low. Therefore, considering their cardiorenal advantages, it is essential to provide clinicians with education and support and to ease the reimbursement criteria for SGLT2i prescriptions.

In the current study, although the mean duration from diagnosis or monotherapy initiation to SGLT2i therapy was shortened, the transition period from dual to triple combination therapy was extended. Triple therapy involving the addition of SGLT2i to two glucose‐lowering agents has shown superior glycemic control and weight reduction compared to placebo or dual therapy. However, several adverse effects associated with the use of SGLT2i in triple therapy have been reported ⁴⁰ , ⁴¹ , ⁴² . Specifically, the risk of hypoglycemic events in SGLT2i triple therapy is nearly twice as high compared to SGLT2i dual therapy. Additionally, individuals on triple therapy are at a higher risk of urinary tract infections and genital infections ⁴⁰ . Moreover, in South Korea, reimbursement for SGLT2i‐containing triple therapy was initially limited to specific combinations (e.g., metformin, SU, and SGLT2i; Table S3). This restriction may have discouraged the use of triple therapy compared to mono or dual therapy with SGLT2i. However, with the expansion of insurance coverage in April 2023, access to triple therapy has become more widely available. Therefore, further research is necessary to evaluate the duration of intensification from dual to SGLT2i‐containing triple therapy following these regulatory changes.

Our study has several limitations. First, GLP‐1RAs are recommended for individuals with CVRD, similar to SGLT2is. However, due to their significantly lower prescription rate (0.3% in 2021, data not shown), we did not include the trends of GLP‐1RA prescriptions in our results. Second, because our study relied on claim data from the NHIS, we were unable to ascertain the status of SGLT2is prescribed on a non‐reimbursable basis such as a triple regimen combination with metformin, DPP‐4i, and SGLT2i or a combination of metformin, thiazolidinedione, and SGLT2i. Lastly, since 2021, the Korean Diabetes Association has recommended SGLT2i prescriptions for individuals with CVRD, and additional approval for chronic heart failure has been obtained from the Korean Ministry of Food and Drug Safety. Furthermore, reimbursement for a triple therapy combination of metformin, DPP‐4i, and SGLT2i, or a combination of metformin, thiazolidinediones, and SGLT2i, has been available since 2023 (Table S3). Therefore, an increase in SGLT2i prescriptions is anticipated, necessitating further study to analyze prescription trends after 2021.

In conclusion, the adoption of SGLT2i therapy is on the rise, especially among individuals with heart failure, accompanied by a notable decrease in time to treatment initiation. However, despite these positive trends, the overall prescription of SGLT2i remains relatively low, even in individuals with CVRD. This finding underscores the need for increased efforts to expand the prescription of SGLT2i with cardiorenal benefits.

DISCLOSURE

K.H.H. has no relevant disclosures. S.S. and E.N. are employees of Boehringer Ingelheim. D.J.K. has received grants or research support from Boehringer Ingelheim, LG Chem, and Novo Nordisk. D.J.K. is an Editorial Board member of the Journal of Diabetes Investigation and a co‐author of this article. To minimize bias, he was excluded from all editorial decision‐making related to the acceptance of this article for publication. The authors meet the criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive payment related to the development of the article. Boehringer‐Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.

Approval of the research protocol: The study protocol was approved by the Institutional Review Board of Ajou University Hospital, Suwon, Republic of Korea (approval no. AJOUIRB‐EXP‐2022‐355).

Informed consent: Because this was a retrospective study, the requirement for informed consent was waived.

Approval date of registry and the registration no. of the study/trial: N/A.

Animal studies: N/A.

Supporting information

Table S1. Classifications of glucose‐lowering drugs.

Table S2. Baseline characteristics of individuals with type 2 diabetes prescribed oral glucose‐lowering drugs.

Table S3. Changes in sodium‐glucose cotransporter 2 inhibitors reimbursement in South Korea.

Figure S1. Proportion of individuals prescribed oral glucose‐lowering drugs by levels of therapy regimen.

Figure S2. Number and proportion of individuals prescribed sodium‐glucose cotransporter 2 inhibitor by levels of therapy regimen.