Abstract
Introduction
Type 2 diabetes mellitus (T2DM) is a global health concern with significant mortality rate associated with comorbidities like diabetic kidney disease (DKD) and cardiovascular disease (CVD). Thus, treatment guidelines recommend first-line treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2Is) and/or glucagon-like peptide 1 (GLP-1) agonists for T2DM with comorbidities. However, in patients when these treatments are not tolerated, contraindicated, or considered expensive, dipeptidyl peptidase 4 inhibitors (DPP4Is) serve as an add-on or alternative for glycemic control without hypoglycemia risk. This study aimed to understand patients’ preferences in three South Asian countries between SGLT2I (medication A) and DPP4I (medication B) and the reasons influencing their preference for effective management of T2DM.
Methods
In this cross-sectional study (November 2021 to November 2022) across India, Taiwan, and the Philippines, patients with T2DM on both SGLT2I and DPP4I or neither completed the survey to identify their medication preferences. Differences in baseline characteristics and preferred medication (chi-squared/Fisher’s exact tests) and potential attributes influencing preferences (logistic regression) were analyzed.
Results
Among 1224 participants, SGLT2I (64.5%) was significantly preferred over DPP4I (35.5%). Mean age of participants was 59.3 years and the majority were female patients/individuals (52.5%), overweight/obese (56.6%), with glycated hemoglobin levels ≥ 7% (57.6%). Common comorbidities included hypertension (62.7%) and dyslipidemia (75.5%); the majority were without history of CVD (83.7%) or CKD (84%). The most prescribed T2DM medication was biguanide (83.9%), followed by combination of SGLT2Is and DPP4Is (51.3%). The most influential attributes were blood sugar reduction (56.9%), reduced heart failure hospitalization (14.4%), and kidney disease risk reduction (12.1%). SGLT2I users showed a higher preference for heart failure hospitalization reduction (16.5%) or weight reduction (11.1%). Country of residence, thiazolidinedione use, and SGLT2I/DPP4I use were significant factors in logistic regression analyses.
Conclusion
Asian patients with T2DM preferred medication profile resembling SGLT2Is over DPP4Is. Understanding patient preferences may aid optimal glycemic control while reducing cardiovascular and renal risks.
Supplementary Information
The online version contains supplementary material available at 10.1007/s13300-025-01770-3.
Keywords: Dipeptidyl peptidase 4 inhibitors, Patient preference, Sodium-glucose cotransporter 2 inhibitors, Type 2 diabetes mellitus
Key Summary Points
| Why carry out this study? |
| Considering the significant mortality rate associated with cardiovascular and kidney disease in patients with type 2 diabetes mellitus (T2DM), treatment guidelines recommend sodium-glucose cotransporter 2 inhibitors (SGLT2Is) and dipeptidyl peptidase 4 inhibitor (DPP4I) which have distinct profiles for cardiovascular and renal benefits beyond effective glycemic control without risk of hypoglycemia. |
| While SGLT2I and DPP4I offer known benefits in glycemic control, there is less research on patient preferences in Asia, where diabetes prevalence is high. |
| What was learnt from this study? |
| Patients from three South Asian countries (India, Taiwan, and the Philippines) preferred SGLT2I over DPP4I. |
| Glycemic control, reduced heart failure hospitalization, and reduction in kidney disease risk were the most common influencing factors for preferring SGLT2I over DPP4I. |
| Overall, patients’ medication preferences are influenced by their disease characteristics and patients primarily consider the benefits of medications in the overall disease management. |
Introduction
Diabetes mellitus (DM) is an expanding global health crisis with devastating consequences [1]. Per the 2021 International Diabetes Federation (IDF) report, DM affected 537 million adults worldwide and the number is expected to rise up to 783 million cases by 2045 [2]. As per the global disease burden study in 2021, the worldwide diabetes prevalence primarily reflected adults with type 2 diabetes mellitus (T2DM), which in 2021 accounted for 96% of diabetes cases and accounted for 95.4% of disability-adjusted life years related to diabetes [3]. In Southeast Asian countries, 90 million adults live with diagnosis of DM and this number is predicted to rise to 152 million (68%) by 2045 [2, 4]. The Southeast Asian region has the second highest number of deaths (1.2 million deaths) attributable to diabetes in adults among the IDF regions [2]. Studies estimate that 30–40% of individuals with T2DM develop diabetic kidney disease (DKD) in around ≥10 years of diabetes duration [5], while cardiovascular disease (CVD) contributes to at least 50% of T2DM-related mortality [6]. Given the increased mortality risk, T2DM requires effective glycemic control for addressing complications of chronic kidney disease (CKD) and CVD [7, 8].
Metformin, the most common biguanide, is the first-line treatment preferred for T2DM, as it effectively lowers blood glucose levels and enhances insulin sensitivity [9]. The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) [10] recommends use of disease-modifying drugs like sodium-glucose cotransporter 2 inhibitors (SGLT2Is) and glucagon-like peptide 1 (GLP-1) agonists as preferred line of treatment after the metformin or in combination in patients with T2DM and along with comorbidities of DKD, high risk of CVD, and heart failure irrespective of glycemic control. DPP4Is are recommended as an add-on treatment to SGLT2Is, in case if GLP-1 agonists are not feasible due to cost, adverse effects, or patient preference [11]. SGLT2Is exhibit cardiovascular benefits, including reduced risks of all-cause mortality, hospitalization, and other CVD events [12], whereas in few studies DPP4Is have not demonstrated beneficial effects on cardiovascular manifestations [13, 14]. SGLT2Is are also associated with greater weight loss benefits along with better glycemic control compared to DPP4Is, which adds to the list of benefits of SGLT2Is, as weight reduction is one of the desired outcomes of such patients [15]. However, patients on SGLT2Is have increased risk of urinary and genital tract infections and diabetic ketoacidosis (DKA) compared with those on DPP4Is [16, 17]. The treatment guidelines prefer SGLT2Is and GLP-1 agonists over DPP4Is in patients with T2DM [2, 8, 18]. The recommendations suggested in guidelines and the marked differences observed between the benefit–risk profile of these two medications may indicate the need to consider patients’ preference per their prime requirements.
Previous studies underline the importance of patient-centered care, emphasizing shared decision-making to enhance satisfaction, adherence, and treatment outcomes [19, 20]. This patient-centric approach is also supported and recommended by ADA and EASD [10]. However, research on patients’ preferences regarding newer glucose-lowering medications is limited. Understanding these aspects is crucial for choosing diabetes management strategies as per individual needs, optimizing adherence, and ultimately improving clinical outcomes. The current study aimed to evaluate the preferences between SGLT2I and DPP4I for the treatment of T2DM and the factors influencing patients’ choice between SGLT2I and DPP4I profiles in South Asian patients with T2DM.
Methods
Study Design
This multicenter, cross-sectional, observational study enrolled 1226 patients and was conducted between November 2021 and November 2022 in centers from three countries in Asia, namely India (n = 4), Taiwan (n = 10), and the Philippines (n = 1) (Supplementary Fig. 1).
The primary objective of this study was to understand patients’ preferences between SGLT2I and DPP4I, to determine potential differences in the reasons for preference between these two treatments, and to evaluate patient demographic characteristics and medical history driving the treatment preference.
Ethical Approval
The study was approved by the Ethics Review Board and written informed consent was obtained from participants. We obtained approval ethics review board for all the three countries, St. Luke’s Medical Centre Institutional Ethics Review Committee for Philippines (IEC no: D1690R00082—PH 5503 IRB), Chang Gung Medical Foundation Institutional Review Board Certificate of Clinical Trial/Research Consent for Taiwan (IEC no: D1690R00082_7406_CCH), and Conscience Independent Ethics Committee review board for India (IEC no: D1690R00082).
Study Population
Consecutive adult patients with diagnosis of T2DM visiting the outpatient department of the study sites who met the inclusion/exclusion criteria were invited to participate in the study. Patients on both SGLT2I and DPP4I treatments or neither of them were included in the study. Patients with T1DM or gestational diabetes were excluded from the study.
Variables and Data Collection
Survey Process
Each patient who consented was provided with a survey questionnaire by their treating physicians or delegates. The survey form was available in both paper and digital format. The forms were developed in English and translated into local languages (Mandarin and Filipino languages for Taiwan and Philippines; Hindi, Bengali, and Tamil for India). Participation ended upon survey completion (Supplementary Fig. 2).
The treating physician collected patients’ demographic and medical history data which included age, gender, education level, height, weight, recent HbA1c level, time since T2DM diagnosis, current medications for T2DM, history of hypertension, dyslipidemia, smoking status, history of cardiac disorders, family medical history of CVD or CKD, latest estimated glomerular filtration rate (eGFR), and albuminuria.
The second part of the survey form described the benefit–risk profiles of the two T2DM agents (medication A, SGLT2I; medication B, DPP4I) in a blinded manner, and patients were asked to indicate their preferred drug profile among the two options. The drug profiles included attributes such as route of administration, effect on HbA1c, weight, risk of hospitalization for heart failure and kidney disease, risk of adverse events [hypoglycemia, DKA, hepatitis, and urogenital tract infections] (Supplementary Table 1). Lastly, the patients were asked to rank the importance of the reasons for their preference of choosing medication A or B on a scale of 0 to 9 (1 being the most important while 9 is the least important) on the basis of the drug attributes listed above.
Statistical Analysis
The sample size of 396 patients was planned by considering the prevalence of 65% of patients with T2DM preferring both or none of the medication profiles (SGLT2I/DPP4I), with a precision limit of 10%, significance level of 5%, and 0% dropout rate to assess the primary objective of SGLT2I being a better choice than DPP4I. The analysis was conducted on the full analysis set (FAS) comprising all enrolled patients, with ineligible ones excluded. Demographic data and medical history were summarized using descriptive statistics. Continuous variables were presented as mean, standard deviation, median, minimum, maximum, 25th and 75th percentiles, while categorical variables were expressed as numbers and percentages. No imputation for missing values was performed. Kolmogorov–Smirnov tests assessed the data distributions for continuous variables. For normally distributed variables, analyses of variance with post hoc Tukey’s tests were used, while non-normally distributed variables were assessed using Kruskal–Wallis tests with Dwass–Steel–Critchlow–Fligner post hoc tests. A two-sided P value of < 0.05 was considered statistically significant.
The study analyzed patient preferences between two medications: Medication A (SGLT2I) and Medication B (DPP4I). Discrete choice experiment technique was used to obtain individual preferences. The number and percentage of patients choosing each medication were summarized. The Clopper–Pearson approach was used to estimate the 95% confidence interval (CI) for the percentage of patients choosing Medication A (SGLT2I). Patients’ preferences were evaluated based on their reasons for choosing an antidiabetic agent, ranked from 1 to 9. The ranks and reasons were compared between the Medication A group and the Medication B group using Chi-square/Fisher’s exact test. A random forest classification algorithm was used to evaluate which of the patient’s demographic characteristics and medical history variables were predictive of patients’ preferences (Medication A vs. B). The out-of-bag (OOB) observations were then used to estimate the prediction error and evaluate variable importance according to the ranking of OOB Gini values. Logistic regression examined odds ratios (OR), 95% CI, and P values for the medication to investigate the relationship between patient reported preference and their demographic/medical history characteristics. While no imputation was performed, missing values were reported and accounted for in the analysis where applicable. Data management and statistical analyses were conducted using SAS version 9.4 software.
Results
Of the 1226 patients enrolled, two did not meet the eligibility criteria. A total of 1224 patients were included in the FAS, of which 400 (32.7%) were from India, 398 (32.5%) were from Taiwan, and 426 (34.8%) were from the Philippines.
Study Population
The mean (SD) age of the patients was 59.3 years (11.49), with 52.5% being female. Approximately, one-third of the patients completed high school education (33.1%) (Table 1). Around 56.6% were considered overweight or obese (BMI > 25 kg/m2, Supplementary Table 2) and had improper control of HbA1c (≥ 7%, 57.6%; Table 2). The duration of diabetes was at least 10 years in 39.3% of patients, and the majority did not have a history of cardiac disorders (83.7%), CKD (84%), or smoking (75.2%). More than half of the patients were diagnosed with hypertension (58.3%) or dyslipidemia (60.3%), and over 95% of these patients were on medication for the same (98.3% and 96.1%, respectively) (Table 3). Biguanides (1027 [83.9%]) were most commonly used medication for T2DM, followed by SGLT2Is and DPP4Is (628 [51.3%] for both) and sulfonylureas (552 [45.1%]) (Table 3).
Table 1.
Patient demographic characteristics by preferred medication
| Variables | All (N = 1224) | DPP4I (n = 434) | SGLT2I (n = 790) | P value |
|---|---|---|---|---|
| Age (years) | ||||
| Mean (SD) | 59.3 (11.49) | 60.0 (10.98) | 59.0 (11.75) | 0.369 |
| Gender, N (%) | ||||
| Female | 642 (52.5) | 206 (47.5) | 436 (55.2) | 0.009 |
| Male | 581 (47.5) | 228 (52.5) | 353 (44.7) | |
| Prefer not to say | 1 (0.1) | 0 | 1 (0.1) | |
| Highest education level, N (%) | ||||
| Elementary | 150 (12.3) | 49 (11.3) | 101 (12.8) | 0.577 |
| High school | 405 (33.1) | 145 (33.4) | 260 (32.9) | |
| Pre-university course | 142 (11.6) | 56 (12.9) | 86 (10.9) | |
| University/graduation | 360 (29.4) | 130 (30.0) | 230 (29.1) | |
| Postgraduate | 81 (6.6) | 36 (8.3) | 45 (5.7) | |
| Not available | 57 (4.7) | 7 (1.6) | 50 (6.3) | |
| Other | 29 (2.4) | 11 (2.5) | 18 (2.3) | |
| BMI (kg/m2) | ||||
| Mean (SD) | 26.3 (7.89) | 25.9 (11.71) | 26.6 (4.59) | < 0.001* |
| BMI group, N (%) | ||||
| ≤ 25 | 531 (43.4) | 214 (49.3) | 317 (40.1) | < 0.001* |
| ≥ 25 | 693 (56.6%) | 220 (50.7) | 473 (59.9) | |
P values for comparison of each characteristic by preferred medication
BMI, body mass index; DPP4I, dipeptidyl peptidase 4 inhibitor; SD, standard deviation; SGLT2I, sodium-glucose cotransporter 2 inhibitors
*Statistically significant
Table 2.
Descriptive statistics of medical history
| Variable; n (%) | All (N = 1224) | India (n = 400) | Philippines (n = 426) | Taiwan (n = 398) | P value |
|---|---|---|---|---|---|
| Most recent HbA1c level within a year | < 0.001* | ||||
| < 7% | 513 (42.4) | 117 (29.3) | 192 (46.7) | 204 (51.3) | |
| ≥ 7% | 696 (57.6) | 283 (70.8) | 219 (53.3) | 194 (48.7) | |
| Time since diagnosis of T2DM | < 0.001* | ||||
| < 5 years | 385 (31.5) | 119 (29.8) | 152 (35.7) | 114 (28.6) | |
| 5–9 years | 358 (29.2) | 152 (38.0) | 104 (24.4) | 102 (25.6) | |
| ≥ 10 years | 481 (39.3) | 129 (32.3) | 170 (39.9) | 182 (45.7) | |
| Current medications for T2DMa | |||||
| Biguanides | 1027 (83.9) | 361 (90.3) | 318 (74.6) | 348 (87.4) | < 0.001* |
| Sulfonylureas | 552 (45.1) | 294 (73.5) | 114 (26.8) | 144 (36.2) | < 0.001* |
| Meglitinide derivatives | 38 (3.1) | 27 (6.8) | 0 | 11 (2.8) | < 0.001* |
| Alpha-glucosidase inhibitors | 29 (2.4) | 17 (4.3) | 0 | 12 (3.0) | < 0.001* |
| TZDs | 221 (18.1) | 128 (32.0) | 39 (9.2) | 54 (13.6) | < 0.001* |
| GLP-1 agonists | 35 (2.9) | 1 (0.3) | 9 (2.1) | 25 (6.3) | < 0.001* |
| DPP4 and SGLT2 inhibitors | 628 (51.3) | 248 (62.0) | 273 (64.1) | 107 (26.9) | < 0.001* |
| Insulin | 314 (25.7) | 91 (22.8) | 126 (29.6) | 97 (24.4) | 0.062 |
| Othera | 8 (0.7) | 0 | 0 | 8 (2.0) | < 0.001* |
| Does the patient have HTN? | < 0.001* | ||||
| Yes, and is on pharmacological treatment | 746 (60.9) | 224 (56.0) | 314 (73.7) | 208 (52.3) | |
| Yes, but not taking any medications for it | 22 (1.8) | 9 (2.3) | 0 | 13 (3.3) | |
| No | 456 (37.3) | 167 (41.8) | 112 (26.3) | 177 (44.5) | |
| Does the patient have dyslipidemia? | |||||
| Yes, and is on pharmacological treatment | 889 (72.6) | 237 (59.3) | 346 (81.2) | 306 (76.9) | |
| Yes, but not taking any medications for it | 35 (2.9) | 4 (1.0) | 3 (0.7) | 28 (7.0) | |
| No | 300 (24.5) | 159 (39.8) | 77 (18.1) | 64 (16.1) | |
| History of smoking or tobacco use in any form? | |||||
| Yes | 304 (24.8) | 67 (16.8) | 94 (22.1) | 143 (35.9) | |
| No | 920 (75.2) | 333 (83.3) | 332 (77.9) | 255 (64.1) | |
| Does the patient’s family have a H/O of CVD or CKD? | |||||
| CKD | 65 (5.3) | 5 (1.3) | 28 (6.6) | 32 (8.0) | |
| CVD | 229 (18.7) | 36 (9.0) | 116 (27.2) | 77 (19.3) | |
| Both | 121 (9.9) | 44 (11.0) | 48 (11.3) | 29 (7.3) | |
| None | 809 (66.1) | 315 (78.8) | 234 (54.9) | 260 (65.3) | |
| Does he/she have any history of cardiac disorders?b | |||||
| Doesn’t have any cardiac issues | 1024 (83.7) | 357 (89.3) | 337 (79.1) | 330 (82.9) | |
| MI | 44 (3.6) | 12 (3.0) | 20 (4.7) | 12 (3.0) | |
| Stroke | 64 (5.2) | 13 (3.3) | 38 (8.9) | 13 (3.3) | |
| Heart failure | 27 (2.2) | 6 (1.5) | 16 (3.8) | 5 (1.3) | |
| Other (describe) | 70 (5.7) | 12 (3.0) | 20 (4.7) | 38 (9.5) | |
| Does the patient have CKD? | |||||
| Yes | 196 (16.0) | 34 (8.5) | 75 (17.6) | 87 (21.9) | |
| No | 1027 (84.0) | 366 (91.5) | 350 (82.4) | 311 (78.1) | |
| What was the patient’s latest eGFR within the last year? | |||||
| G1—normal or highc | 447 (36.5) | 196 (49.0) | 93 (21.8) | 158 (39.7) | |
| G2—mildly decreasedc | 330 (27.0) | 77 (19.3) | 97 (22.8) | 156 (39.2) | |
| G3a—mildly to moderately decreasedc | 94 (7.7) | 13 (3.3) | 32 (7.5) | 49 (12.3) | |
| G3b—moderately to severely decreasedc | 48 (3.9) | 7 (1.8) | 21 (4.9) | 20 (5.0) | |
| G4—severely decreasedc | 20 (1.6) | 2 (0.5) | 11 (2.6) | 7 (1.8) | |
| G5—kidney failurec | 3 (0.2) | 0 | 2 (0.5) | 1 (0.3) | |
| Not available | 282 (23.0) | 105 (26.3) | 170 (39.9) | 7 (1.8) | |
| What was the patient’s latest eGFR within the last year? | |||||
| ≥ 60 mL/min/1.73 m2 | 777 (63.5) | 273 (68.3) | 190 (44.6) | 314 (78.9) | |
| < 60 mL/min/1.73 m2 | 165 (13.5) | 22 (5.6) | 66 (15.5) | 77 (19.3) | |
| Not available | 282 (23.0) | 105 (26.3) | 170 (39.9) | 7 (1.8) | |
| What was the patient’s latest albuminuria within the last year? | |||||
| A1—normal to mildly increasedd | 544 (44.4) | 177 (44.3) | 84 (19.7) | 283 (71.1) | |
| A2—moderately increasedd | 167 (13.6) | 81 (20.3) | 29 (6.8) | 57 (14.3) | |
| A3—severely increasedd | 32 (2.6) | 3 (0.8) | 4 (0.9) | 25 (6.3) | |
| Not available | 481 (39.3) | 139 (34.8) | 309 (72.5) | 33 (8.3) | |
P value for comparison of HbA1c level by region. India vs. Philippines, P < 0.001; India vs. Taiwan, P < 0.001, Philippines vs. Taiwan, P = 0.200
CKD, chronic kidney disease; CVD, cardiovascular disease; DM, diabetes mellitus; DPP4I, dipeptidyl peptidase 4 inhibitor; eGFR, estimated glomerular filtration rate; GLP-1, glucagon-like peptide 1; HbA1c , glycated hemoglobin; H/O, history of; HTN, hypertension; MI, myocardial infarction; SGLT2I, sodium glucose transport protein 2 inhibitor; T2DM, type 2 diabetes mellitus; TZD, thiazolidinedione
*Statistically significant
aThis option represents subjects who used other methods as current medications, such as diet control, or even did not use any medication
bA patient may have multiple current medications or history of cardiac disorders
cG1—normal or high (≥ 90 mL/min/1.73 m2), G2—mildly decreased (60–89 mL/min/1.73 m2), G3a—mildly to moderately decreased (45–59 mL/min/1.73 m2), G3b—moderately to severely decreased (30–44 mL/min/1.73 m2), G4—severely decreased (15–29 mL/min/1.73 m2), G5—kidney failure (< 15 mL/min/1.73 m2)
dA1—normal to mildly increased (< 30 mg/g/< 3 mg/mmol), A2—moderately increased (30–300 mg/g / 3–30 mg/mmol), A3—severely increased (> 300 mg/g / > 30 mg/mmol)
Table 3.
Descriptive statistics of medical history by preferred medication
| Variable, n (%) | All (N = 1224) | DPP4I (n = 434) | SGLT2I (n = 790) | P value |
|---|---|---|---|---|
| Most recent HbA1c level within a year | 0.483 | |||
| < 7% | 513 (42.4) | 175 (41.1) | 338 (43.2) | |
| ≥ 7% | 696 (57.6) | 251 (58.9) | 445 (56.8) | |
| Time since diagnosis of T2DM | 0.078 | |||
| < 5 years | 385 (31.5) | 127 (29.3) | 258 (32.7) | |
| 5–9 years | 358 (29.2) | 144 (33.2) | 214 (27.1) | |
| ≥ 10 years | 481 (39.3) | 163 (37.6) | 318 (40.3) | |
| Current medications for T2DM | ||||
| Biguanides | 1027 (83.9) | 365 (84.1) | 662 (83.8) | 0.890 |
| Sulfonylureas | 552 (45.1) | 224 (51.6) | 328 (41.5) | 0.001* |
| Meglitinide derivatives | 38 (3.1) | 15 (3.5) | 23 (2.9) | 0.599 |
| Alpha-glucosidase inhibitors | 29 (2.4) | 3 (0.7) | 26 (3.3) | 0.004* |
| TZDs | 221 (18.1) | 53 (12.2) | 168 (21.3) | < 0.001* |
| GLP-1 agonists | 35 (2.9) | 10 (2.3) | 25 (3.2) | 0.388 |
| DPP4 and SGLT2 inhibitors | 628 (51.3) | 205 (47.2) | 423 (53.5) | 0.035* |
| Insulin | 314 (25.7) | 102 (23.5) | 212 (26.8) | 0.202 |
| Othera | 8 (0.7) | 2 (0.5) | 6 (0.8) | 0.720 |
| Does the patient have HTN? | 0.007* | |||
| Yes, and is on pharmacological treatment | 746 (60.9) | 241 (55.5) | 505 (63.9) | |
| Yes, but not taking any medications for it | 22 (1.8) | 6 (1.4) | 16 (2.0) | |
| No | 456 (37.3) | 187 (43.1) | 269 (34.1) | |
| Does the patient have dyslipidemia? | < 0.001* | |||
| Yes, and is on pharmacological treatment | 889 (72.6) | 279 (64.3) | 610 (77.2) | |
| Yes, but not taking any medications for it | 35 (2.9) | 21 (4.8) | 14 (1.8) | |
| No | 300 (24.5) | 134 (30.9) | 166 (21.0) | |
| History of smoking or tobacco use in any form? | 0.091 | |||
| Yes | 304 (24.8) | 120 (27.6) | 184 (23.3) | |
| No | 920 (75.2) | 314 (72.4) | 606 (76.7) | |
| Does the patient’s family have a H/O of CVD or CKD? | 0.037* | |||
| CKD | 65 (5.3) | 28 (6.5) | 37 (4.7) | |
| CVD | 229 (18.7) | 64 (14.7) | 165 (20.9) | |
| Both | 121 (9.9) | 41 (9.4) | 80 (10.1) | |
| None | 809 (66.1) | 301 (69.4) | 508 (64.3) | |
| Does he/she have any history of cardiac disorders?b | ||||
| Doesn’t have any cardiac issues | 1024 (83.7) | 377 (86.9) | 647 (81.9) | 0.025* |
| MI | 44 (3.6) | 19 (4.4) | 25 (3.2) | 0.275 |
| Stroke | 64 (5.2) | 15 (3.5) | 49 (6.2) | 0.039* |
| Heart failure | 27 (2.2) | 5 (1.2) | 22 (2.8) | 0.063 |
| Other (describe) | 70 (5.7) | 19 (4.4) | 51 (6.5) | 0.134 |
| Does the patient have CKD? | 0.043* | |||
| Yes | 196 (16.0) | 57 (13.2) | 139 (17.6) | |
| No | 1027 (84.0) | 376 (86.8) | 651 (82.4) | |
| What was the patient’s latest eGFR within the last year? | 0.369 | |||
| G1—normal or highc | 447 (36.5) | 152 (35.0) | 295 (37.3) | |
| G2—mildly decreasedc | 330 (27.0) | 109 (25.1) | 221 (28.0) | |
| G3a—mildly to moderately decreasedc | 94 (7.7) | 34 (7.8) | 60 (7.6) | |
| G3b—moderately to severely decreasedc | 48 (3.9) | 10 (2.3) | 38 (4.8) | |
| G4—severely decreasedc | 20 (1.6) | 6 (1.4) | 14 (1.8) | |
| G5—kidney failurec | 3 (0.2) | 0 | 3 (0.4) | |
| Not available | 282 (23.0) | 123 (28.3) | 159 (20.1) | |
| What was the patient’s latest eGFR within the last year? | 0.415 | |||
| ≥ 60 mL/min/1.73 m2 | 777 (63.5) | 261 (60.1) | 516 (65.3) | |
| < 60 mL/min/1.73 m2 | 165 (13.5) | 50 (11.5) | 115 (14.6) | |
| Not available | 282 (23.0) | 123 (28.3) | 159 (20.1) | |
| What was the patient’s latest albuminuria within the last year? | < 0.001* | |||
| A1—normal to mildly increasedd | 544 (44.4) | 246 (56.7) | 298 (37.7) | |
| A2—moderately increasedd | 167 (13.6) | 49 (11.3) | 118 (14.9) | |
| A3—severely increasedd | 32 (2.6) | 10 (2.3) | 22 (2.8) | |
| Not available | 481 (39.3) | 129 (29.7) | 352 (44.6) | |
P values for comparison of each characteristic by preferred medication
CKD, chronic kidney disease; CVD, cardiovascular disease; DM, diabetes mellitus; DPP4I, dipeptidyl peptidase 4 inhibitor; eGFR, estimated glomerular filtration rate; GLP-1, glucagon-like peptide 1; HbA1c, glycated hemoglobin; H/O, history of; HTN, hypertension; MI, myocardial infarction; SGLT2I, sodium glucose transport protein 2 inhibitor; T2DM, type 2 diabetes mellitus; TZD, thiazolidinedione
*Statistically significant
aThis option represents subjects who used other methods as current medications, such as diet control, or even did not use any medication
bA patient may have multiple current medications or a history of cardiac disorders
cG1—normal or high (≥ 90 mL/min/1.73 m2), G2—mildly decreased (60–89 mL/min/1.73 m2), G3a—mildly to moderately decreased (45–59 mL/min/1.73 m2), G3b—moderately to severely decreased (30–44 mL/min/1.73 m2), G4—severely decreased (15–29 mL/min/1.73 m2), G5—kidney failure (< 15 mL/min/1.73 m2)
dA1—normal to mildly increased (< 30 mg/g, < 3 mg/mmol), A2—moderately increased (30–300 mg/g, 3–30 mg/mmol), A3—severely increased (> 300 mg/g, > 30 mg/mmol)
Patients’ Preferred Medication and Baseline Characteristics
Overall, preference for SGLT2I was significantly high compared to DPP4I (64.5% [95% CI 61.8–67.2%] vs. 35.5%; P < 0.001). The preference for SGLT2I was highest among patients in the Philippines (80%, P < 0.001), followed by Taiwan (58%, P = 0.002), and India (54.5%, P = 0.080) (Supplementary Table 4). The overall preference for SGLT2I remained high regardless of whether the HbA1c levels were well controlled (65.9%, [95% CI 61.6–70%]) or not (63.9%, [95% CI 60.2–67.5%]). Patients preferring the profile of SGLT2I were mostly female patients/individuals (55.2% vs. 47.5%, P = 0.009) and significantly overweight or obese (BMI ≥ 25 kg/m2; 59.9% vs. 50.7%, P = 0.002) compared with those preferring DPP4I’s profile. There were no significant differences observed for other socio-demographic characteristics based on the patients’ choice of medication (Supplementary Table 2).
A significantly greater number of patients preferring SGLT2I’s profile reported being diagnosed with hypertension (63.9% vs. 55.5%; P = 0.007) and dyslipidemia (77.2% vs. 64.3%; P < 0.001) compared to those preferring DPP4I’s profile. Similarly, a considerabe number of patients with CKD than those without CKD preferred SGLT2Is (17.6%, P = 0.043). Patients without cardiac disorders preferred DPP4Is (86.9%, P = 0.025), whereas those with stroke preferred SGLT2Is (6.2%, P = 0.039). HbA1c level, smoking history, and latest eGFR levels were similar between both the groups (Table 3). The majority of patients who chose DPP4I [56.7% vs. 37.7%] had normal to mildly increased albuminuria (< 30 mg/g/ < 3 mg/mmol) than those who preferred SGLT2I’s profile, but a significant proportion had no available albuminuria data (29.7% vs. 44.6%, respectively). A significantly greater number of patients were on sulfonylureas among those who preferred DPP4Is compared to those who preferred SGLT2I (51.6% vs. 41.5%, P = 0.001), whereas those using alpha-glucosidase inhibitors, thiazolidinedione (TZDs), or a combination of DPP4Is and SGLT2Is preferred SGLT2I’s profile (Table 3).
Key Attributes Influencing Patient Preferences
The three most influential attributes (rank 1—most important reason) observed were reduction in blood sugar levels (56.9% of patients), reduction in hospitalization events due to heart failure (14.4% of patients), and kidney disease risk reduction (12.1% of patients). Lifestyle counselling specific to the drug (40.7% of patients), reduction of body weight (20.3% of patients), and risk of developing hepatitis (16.7% of patients) were considered least influential attributes (rank 9—least important reason) (Fig. 1 and Supplementary Table 3).
Fig. 1.
Reasons influencing patients’ preferences for medications
Ranking of Attributes Between Treatments
Irrespective of medication preferences, the reduction of blood sugar levels was ranked the most influential attribute with no significant difference between the two medications (57% and 56.7% of patients preferring SGLT2I or DPP4I, respectively). A significantly higher proportion of patients who preferred SGLT2I ranked risk of hospitalization due to heart failure (16.5% vs. 10.6%, P < 0.001) followed by risk of hypoglycemia (11.1% vs. 5.8%, P < 0.001) and reduction of body weight (1.8% vs. 7%, P < 0.001). The kidney disease risk reduction (13.7% vs. 9.2%, P = 0.13) and reduction of blood sugar levels (57.0% vs. 56.7%, P = 0.152) were also higher in the group preferring SGLT2I compared to DPP4I, but with no statistical significance (Fig. 2 and Supplementary Table 3).
Fig. 2.
Reasons influencing preferences of patients with T2DM (Medication A vs. Medication B). A By medication. B By attributes. Note: P < .001 for ranks 1, 2, 3, 8, 9. Rank 4, P = 0.061; Rank 5, P = 0.068; Rank 6, P = 0.099; Rank 7, P = 0.001. Except for reduction of blood sugar parameter (P = 0.152) and kidney disease risk reduction (P = 0.130), P < .001 for all other parameters. DPP4I, dipeptidyl peptidase 4 inhibitors; SGLT2, sodium-glucose cotransporter 2 inhibitors; T2DM, type 2 diabetes mellitus
Factors Influencing Patient Preferences
Among all the variables assessed, the country of residence, latest eGFR, current use of TZDs, and simultaneous use of SGLT2Is and DPP4Is were the factors with relatively strong impact (OOB Gini value of 0.01403) on the patient’s preference for medication (Supplementary Fig. 3).
In univariate logistic regression analysis, patients using TZDs, and those using both SGLT2I and DPP4I had higher odds of choosing SGLT2I (OR 1.94 [95% CI 1.39–2.71] and 1.29 [95% CI 1.02–1.63], respectively). Furthermore, having an eGFR below 60 mL/min/1.73 m2 (OR 1.16 [95% CI 0.81–1.67]) was associated with an increased chance of preferring SGLT2I; however, this association was not statistically significant. In multivariable logistic regression, TZDs users (adjusted OR 1.73 [95% CI 1.18–2.54] and SGLT2I and DPP4I users (adjusted OR 1.44 [95% CI 1.06–1.95]) remained significant factors driving patient preference of choosing SGLT2I (Table 4).
Table 4.
Logistic regression analysis for associations of baseline characteristics with preference to medication A
| Crude OR (95% CI) | P value | Adjusted OR (95% CI) | P value | |
|---|---|---|---|---|
| Country | ||||
| Philippines | Reference | Reference | ||
| India | 0.30 (0.22–0.41) | < 0.001* | 0.48 (0.31–0.73) | 0.001* |
| Taiwan | 0.35 (0.25–0.47) | < 0.001* | 0.41 (0.28–0.60) | < 0.001* |
| Currently using thiazolidinediones for T2DM | ||||
| No | Reference | Reference | ||
| Yes | 1.94 (1.39–2.71) | < 0.001* | 1.73 (1.18–2.54) | 0.005* |
| Currently using DPP4I and SGLT2I for T2DM | ||||
| No | Reference | Reference | ||
| Yes | 1.29 (1.02–1.63) | 0.035* | 1.44 (1.06–1.95) | 0.018* |
| Latest eGFR within the last year | ||||
| ≥ 60 mL/min/1.73 m2 | Reference | Reference | ||
| < 60 mL/min/1.73 m2 | 1.16 (0.81–1.67) | 0.415 | 1.03 (0.70–1.51) | 0.891 |
CI, confidence interval; DPP4I, dipeptidyl peptidase 4 inhibitors; eGFR, estimated glomerular filtration rate; OR, odds ratio; SGLT2I, sodium-glucose cotransporter 2 inhibitors; T2DM, type 2 diabetes mellitus
*Statistically significant (P < 0.05)
Discussion
This study investigated the factors influencing choices of Asian patients with T2DM between drug profiles of SGLT2Is and DPP4Is as the second-line oral antidiabetic treatment. The findings reveal a significant preference for SGLT2Is, driven primarily by their clinical benefits in glycemic control, cardiorenal protection, and weight management. Additionally, the study highlights that patients’ demographic and clinical characteristics influence these preferences. These observations are consistent with previous studies in Singapore and Latin America, which also reported higher SGLT2I preferences [21, 22]. However, the lower preference observed in our study (65%) compared to the studies in Singapore and Latin America (over 80%) could be attributed to the variations in study population included from the three different regions and the patient characteristics observed in our study. Weight reduction is a key benefit of SGLT2Is [15]. The smaller proportion of patients with overweight/obesity observed in our study (56.5%) compared to Latin-American study (86.9%) likely contributed to a lower SGLT2I preference [22]. Additionally, the lack of all-cause mortality reduction as an attribute in our survey, which was highly valued in the Singapore study, might have underestimated SGLT2I preference [21]. In a retrospective, real-world study of treatment patterns in Korea, prescriptions of SGLT2Is and DPP4Is have increased gradually based on the patients’ characteristics of age, renal function, and glycated hemoglobin. Therefore, patient clinicodemographic characteristics may influence the preference of treatment [23].
In our study, for the patient demographics by preferred medications, though there is a risk of genital infections with the use of SGLT2Is, the proportion of female patients/individuals choosing SGLT2I was observed to be higher and statistically significant. Studies have demonstrated that female patients/individuals diagnosed with T2DM are more prone to genital infections [24] and the risk of infection increases by three- to five-fold in patients preferring SGLT2I [25, 26]. However, in our study a greater proportion of female patients/individuals preferred SGLT2I.
Additionally in our study, patients with overweight/obesity and high BMI (> 30 kg/m2) were also found to prefer SGLT2I over DPP4I. The preference observed for SGLT2I is likely driven by its effective weight reduction, especially in patients with T2DM [15, 27].
The subgroup analysis for assessing country-wise preference of medications demonstrated highest SGLT2I preference in the Philippines (80%), followed by Taiwan (58%) and India (55%). The remarkably high preference observed for SGLT2Is in the Philippines among the three countries could be due to potential contributing factors of high prevalence of hypertension (73.7%) and family history of CKD/CVD (45.1%), aligning with the established cardiovascular and renal benefits of SGLT2Is [28, 29]. In addition to patient’s medical history, treatment guidelines, medication availability, cost, and affordability across different healthcare systems might influence the choice of treatment [18, 30, 31]. In a real-world setting among the Taiwanese population with T2DM, SGLT2Is were highly preferred over DPP4Is because of cost-effectiveness [32]. A few studies in the Indian population also suggested that SGLT2Is was preferred more due to its superior efficacy of CVD/CKD compared to DPP4Is and convenience of a fixed dose combination (SGLT2I + DPP4I) for the management of T2DM [33, 34]. In contrast, findings in our study for Indian patients suggest that SGLT2I preference was not statistically significant (54.5%, P = 0.080) compared to the other two regions. It is important to acknowledge that our study did not assess patients’ income levels or real-world medication costs, and both treatment options were presented at equal cost in the survey. In clinical practice, affordability is a major determinant of adherence and treatment selection, particularly in regions where SGLT2Is remain more expensive than DPP4Is and may not be fully covered by healthcare systems. Future studies incorporating economic factors and affordability assessments would provide a more comprehensive understanding of medication preference patterns. Such insights may help optimize treatment strategies by considering both clinical benefits and patients’ financial constraints.
The selection of medication by patients or healthcare providers is driven by a combination of factors, and not just a single attribute. In our study, the most important factors influencing patient preference were glycemic control and cardiorenal protection, thus favoring the profile of SGLT2Is. Notably, patients choosing SGLT2Is prioritized heart failure hospitalization and weight reduction, with a higher proportion of patients ranking reduction in risk of kidney disease as the most important attribute. Our findings align with studies showing HbA1c, hypoglycemia risk, cardiovascular risk, risk of gastrointestinal problems, weight change, mode of administration, and dosing frequency as key attributes for T2DM medication choice [35, 36].
Additionally, in our study a greater number of patients considered lowering the risk of developing kidney disease as an important factor for choosing SGLT2Is, despite the risk of genital infections and DKA associated with SGLT2Is. The willingness to accept these potential side effects/risks in exchange for the perceived benefits of cardiorenal protection and weight management, clearly states patients’ priorities and their understanding of the risk–benefit profile of available treatment options. However, it is crucial that patients be informed of all the associated risk factors and discuss them with their healthcare providers. Along with genital infections reported in patients with T2DM on SGLT2I therapy, other factors like circumcision, menopause, and personal hygiene may also play an important role. Though genital infections were not reported as a major concern in our study, further research exploring individual risk perception and patient education regarding potential side effects is warranted.
This study acknowledges the limitations of self-reported data. However, similar demographics to other studies suggest minimal bias. The study population is restricted to Asian countries, limiting generalizability to other regions with diverse demographics and healthcare systems. Even though the study included participants who had prior experience and familiarity of the benefit–risk profiles of both the medications or none of them, patients preferred SGLT2I over DPP4I and the results of OOB and logistic regression analysis further corroborated this finding. The cross-sectional study design does not establish causative relationships between patient characteristics and medication preference. The cost-effectiveness, access, and availability of treatments were not analyzed in this study, which could offer further valuable insights into patients’ preferences. While the ranking order in the questionnaire might have influenced responses, the overall trends align with medication features and patient concerns.
Future studies could utilize objective data collection methods like longitudinal studies with diverse population and broader demographics, which would demonstrate the real-world scenario of treatment patterns and preferences. Additionally, exploring cultural influences using qualitative approaches can help healthcare providers and patients understand treatment preferences better and help improve treatment outcomes.
Conclusions
This study demonstrates a clear preference for SGLT2I over DPP4I among Asian patients with T2DM, which may be influenced by their perception of its effectiveness in HbA1c reduction and managing associated risk factors. However, as this study did not assess treatment efficacy directly, the findings should be interpreted as a reflection of patient preferences rather than clinical outcomes. Patients’ medication preferences are influenced by their disease characteristics and patients primarily consider the benefits of medications in the overall disease management. Future research delving deeper into cultural influences, individual risk perception, and healthcare systems is required to personalize treatment recommendations and empower patients to make informed decisions about their T2DM management.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgments
Medical Writing and Editorial Assistance
The authors would like to thank Sonali Satam, PhD for medical writing assistance and Uma Kundu, MPharm for editorial support from SIRO Medical Writing Pvt. Ltd, India, and was funded by AstraZeneca Pharma India Limited.
Authorship
All authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this article, ensuring accuracy and completeness of the work, and have approved the final version for publication.
Author Contributions
Mangesh Tiwaskar and Chi Min Hwu were involved in conceptualization, investigation, methodology, project administration, supervision, data validation, visualization, writing (reviewing and editing). Marcelo Lim and Iris Chang were involved in conceptualization, methodology, data visualization, writing (reviewing and editing). Apeksha Bhandary was involved in conceptualization, methodology, resources, data visualization, writing (reviewing and editing).
Funding
This study and the journal’s Rapid Service Fee was funded by AstraZeneca Pharma India Limited.
Data Availability
All data generated or analyzed during this study are included in this published article and its supplementary information files.
Declarations
Conflict of Interest
Dr Mangesh Tiwaskar: Nothing to disclose. Dr Chii-Min Hwu: Received manuscript development funding for the current study from AstraZeneca, grant support from Sanofi, Eli Lilly, MSD, consulting fees from Novo Nordisk, honoraria and speaker bureau fees from Eli Lilly, Sanofi, Zuellig, Amgen. Dr Marcelo Lim: Received support for medical writing from AstraZeneca. Dr Apeksha Bhandary and Dr Iris Chang are employees of AstraZeneca Pharma India Limited and AstraZeneca Pharma Taiwan Limited and may own stock and stock options.
Ethical Approval
The study was approved by the Ethics Review Board and written informed consent was obtained from participants. We obtained approval ethics review board for all the three countries, St. Luke’s Medical Centre Institutional Ethics Review Committee for Philippines (IEC no. D1690R00082—PH 5503 IRB), Chang Gung Medical Foundation Institutional Review Board Certificate of Clinical Trial/Research Consent for Taiwan (IEC no. D1690R00082_7406_CCH), and Conscience Independent Ethics Committee review board for India (IEC no. D1690R00082).
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
All data generated or analyzed during this study are included in this published article and its supplementary information files.