FormalPara Key Summary Points

Evidence of a direct comparison between dipeptidyl-peptidase 4 inhibitors (DPP-4is) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) regarding the patients’ quality of life (QOL) and treatment satisfaction remains lacking.

This sub-analysis of a randomized-controlled trial with an SGLT2i, luseogliflozin, and DPP-4is compared their effects on QOL and treatment satisfaction of patients, measured by Oral Hypoglycemic Agent Questionnaire (OHA-Q) version 2.

When luseogliflozin or DPP-4is were initiated in drug-naïve patients, total and somatic symptom scores were significantly higher in the DPP-4i group than in the luseogliflozin group.

When luseogliflozin or DPP-4is were added in patients who were treated with other OHAs, changes in total OHA-Q and treatment convenience were significantly greater in the luseogliflozin group than in the DPP-4i group.

The QOL related to safety or glycemic control was comparable between the groups

Introduction

Quality of life (QOL) of patients is an important factor in continuing diabetes management. Current Japanese guidelines recommend pharmacotherapy to maintain patients’ QOL in addition to the consideration of appropriate targets for glucose control, pathological conditions such as obesity, safety, additional benefits in terms of complications, and other relevant factors to prevent or reduce the occurrence of complications [1]. The QOL of patients is also the focus of the consensus statement of the American Diabetes Association and European Association for the Study of Diabetes in addition to presence of pathological conditions and efficacy, side effects, and costs of medical agents [2]. In particular, satisfaction with prescribed antidiabetic agents should be considered. Ishii et al. constructed the Oral Hypoglycemic Agent Questionnaire (OHA-Q) [3, 4] to assess the QOL and treatment satisfaction of patients taking oral hypoglycemic agents (OHAs).

Dipeptidyl peptidase-4 inhibitors (DPP-4is) are a class of OHAs with a relatively low risk of hypoglycemia [5, 6]. Since DPP-4is were reported to be more effective in the Asian population [7], they are most frequently prescribed among OHAs in Japan [8,9,10]. The QOL and treatment satisfaction, assessed using the OHA-Q, in patients who were treated with DPP-4is, was as high as or even higher than that in patients who were taking conventional oral antidiabetic agents (sulfonylureas [SUs], biguanides [BGs], α-glucosidase inhibitors [αGIs], and thiazolidine [TZDs]) [11]. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a new class of OHA with a safe profile [12], and its use is increasing [8, 13]. Use of SGLT2i may further increase in the future because of additional approval for heart failure or chronic kidney disease in Japan. A single-arm study demonstrated that the SGLT2i dapagliflozin improved patient treatment satisfaction, as assessed using the OHA-Q [4].

However, no study had directly compared the effect of DPP-4is and SGLT2is, especially in terms of QOL and treatment satisfaction of patients with type 2 diabetes mellitus. The J-SELECT study demonstrated the overall and multiple aspects of the efficacy of luseogliflozin compared with DPP-4is in the mid-/long-term, regardless of body mass index (BMI) or age [14]. This article reports the results of a sub-analysis of the J-SELECT study comparing patient QOL and treatment satisfaction between that with DPP-4is and luseogliflozin.

Methods

The J-SELECT study was a multicenter, open-label, randomized-controlled trial. The details have been published in our previous paper [14]. Patient enrollment was conducted between January 2018 and November 2020 at 88 medical institutions in Japan (Supplementary Materials Table 1), and each enrolled patient was followed for 12 months. The trial protocol was first approved by the Japan Physicians Association Institutional Review Board (reference number: 007-1710) according to the Ethics Guidelines for Medical and Health Research Involving Human Subjects issued by the Ministry of Health, Labour, and Welfare in Japan. Participation of each medical institution for study implementation was inspected and approved collectively by the Japan Physicians Association Institutional Review Board or by the ethics review board in each institution. The list of ethics review boards which first approved the participation of each medical institution is shown in Supplementary Materials Table 1. Before enrolling the first patient, this study was registered at the University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR) (UMIN000030128) on November 27, 2017. Subsequently, following the enforcement of a new law, ‘the Clinical Trials Act,’ in April 2018 in Japan, this study and its protocols were again inspected and approved by the Certified Clinical Research Review Board of Toho University (reference no. THC18008), which obtained certification from the Minister of Health, Labour, and Welfare in Japan. After approval from the certified review board, this study was registered in the Japan Registry of Clinical Trials (jRCT) (jRCTs031180241) on March 15, 2019, which is the clinical trial registration developed by the Ministry of Health, Labour, and Welfare in Japan, according to the requirements of the Clinical Trials Act. The study was conducted in accordance with the principles of the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, the Clinical Trials Act, and other relevant legal regulations in Japan.

Table 1 Total and subscale scores of OHA-Q in drug-naïve subgroup
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This study recruited patients with type 2 diabetes mellitus who were drug-naïve or treated with antidiabetic agents other than SGLT2is and DPP-4is. The main inclusion criteria and exclusion criteria were as follows. Inclusion criteria were (1) patients with type 2 diabetes mellitus, (2) male and female aged ≥ 20 years and < 75 years when giving their consent, (3) patients who did not use antidiabetic agents within 8 weeks before consenting or patients who used antidiabetic agents other than SGLT2is and DPP-4is and who did not change their usage and dose within 8 weeks before consenting, and (4) patients with glycated hemoglobin A1c (HbA1c) ≥ 6.5% but ≤ 10.0% within 8 weeks before consenting. Exclusion criteria were (1) patients who used insulin or GLP-1 analogs within 8 weeks before consenting and (2) patients with cardiac disease (myocardial infarction, cerebral infarction, or stroke), severe liver disease, renal disease, unstable hypertension or dyslipidemia, dehydration, urinary tract infection, genital infection, or geriatric syndrome (sarcopenia, cognitive dysfunction, impairment in activities of daily living, etc.). The inclusion and exclusion criteria have been described in detail in our previous paper [14]. The registered patients were randomly assigned to the luseogliflozin and DPP-4i groups in an approximately 1:1 ratio. The patients assigned to the luseogliflozin group and DPP-4i group received luseogliflozin or daily DPP-4i (sitagliptin, vildagliptin, linagliptin, alogliptin, anagliptin, teneligliptin, and saxagliptin), respectively, for 52 weeks. The dose and usage of luseogliflozin or DPP-4is were according to instructions for each package insert. Once-weekly DPP-4is (trelagliptin and omarigliptin) were prohibited even in the DPP-4i group. During the observation period, till week 24, medication of anti-diabetic agents was not changed, in principle. However, if HbA1c of 8.5% or higher was measured twice consecutively, or after the week 24, rescue therapy was allowed in the following steps: (1) dose change in luseogliflozin or DPP-4is; (2) addition of oral hyperglycemic agents. Even in the rescue therapy, use of SGLT2i other than luseogliflozin and any DPP-4is was prohibited in the luseogliflozin group and use of any SGLT2i and DPP-4is other than as specified above. The patients were followed up to baseline (week 0) before the initiation and 2, 24, and 52 weeks after the initiation of the study agents. The details of observation schedules and items have been described in our previous paper [14].

The primary endpoint was the proportion of patients who improved in three or more endpoints among the five composite endpoints (HbA1c, weight, estimated glomerular filtration rate, systolic blood pressure, and pulse rate) from baseline to week 52. Secondary endpoints included blood tests and urine tests. A full list of the secondary endpoints and the results of the primary endpoint and laboratory test-related secondary endpoints has been reported in our previous paper [14]. As a secondary endpoint, the OHA-Q version 2 [3, 4] was administered to the enrolled patients 0, 24, and 52 weeks after initiation, with permission for use from Hitoshi Ishii [3]. Since the OHA-Q is used to assess the QOL and treatment satisfaction of patients using OHAs, it was not administered at week 0 for drug-naïve patients. OHA-Q version 2 consists of 23 items and 3 subscales: subscale 1 “treatment convenience” (items 1–9), subscale 2 “somatic symptom” (items 11–21), and subscale 3 “satisfaction” (items 10, 22, and 23). The items in the OHA-Q are rated on a 4-point Likert scale, and the scores for each item, scores for the treatment convenience, somatic symptom, and satisfaction subscales, and the total score range from to 0–3, 0–27, 0–33, 0–9, and 0–69, respectively. Higher score in the OHA-Q means better QOL or treatment satisfaction.

Statistical analysis was performed using the full analysis set population, which included all patients registered in this study who were subsequently randomized to one of the study treatments. Patients who severely violated the study protocol or without any data for the primary endpoint (23 patients in the luseogliflozin group and 27 patients in the DPP-4i group) were excluded. A detailed patient flow diagram was shown in our previous paper [14]. The Wilcoxon rank-sum test was performed for between-group comparisons, and Wilcoxon signed-rank test was performed for intragroup comparisons from baseline to postoperative OHA-Q scores for each item. A two-sample t-test was performed for between-group comparison of measurements, and a one-sample t-test was performed for intragroup comparison from baseline to postoperative total and subscale OHA-Q scores. Correlation analysis was performed using Pearson’s correlation coefficients. All p values were two sided, and p  < 0.05 was considered statistically significant. Missing values were not compensated in this study. To avoid bias, a third-party entity (Soiken Inc., Osaka, Japan) conducted all statistical analyses, using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA).

Results

A total of 623 patients were registered in this study; 311 and 312 patients were randomized to the luseogliflozin and DPP-4i groups, respectively. The detailed flow of patient screening, enrollment, and observation has been published in our previous paper [14]. Since the OHA-Q is designed to assess the QOL and treatment satisfaction of patients who are using OHAs, it was not administered for drug-naïve patients at baseline. The OHA-Q scores in patients who were drug-naïve at baseline and with monotherapy with luseogliflozin or DPP-4i throughout the observation period (126 patients in the luseogliflozin group and 130 patients in the DPP-4i group/drug-naïve subgroup) were calculated as post hoc. Total scores at 52 weeks (p = 0.048) and somatic symptom scores at 52 weeks (p = 0.005) were significantly lower in the luseogliflozin group than in the DPP-4i group (Table 1). Treatment convenience and satisfaction scores were not significantly different between the two groups.

Patients who were treated with OHAs other than SGLT2is and DPP-4is at baseline answered to the OHA-Q at baseline (109 patients in the luseogliflozin group and 95 patients in the DPP-4i group/add-on subgroup). The total and subscale scores of OHA-Q were well balanced in the add-on subgroup at baseline (Table 2). Changes in OHA-Q scores from baseline could be calculated only in the add-on subgroup. When luseogliflozin was added to the previously used OHAs, all the total and subscale scores of OHA-Q significantly increased from baseline to 24 and 52 weeks (Table 2). However, when DPP-4is were added to the previously used OHAs, the total scores from baseline to 52 weeks, somatic symptom score from baseline to 24 and 52 weeks, and satisfaction score from baseline to 24 and 52 weeks significantly increased. The change in the total score from baseline to 24 weeks (p = 0.030) and change in treatment convenience score from baseline to 24 weeks (p = 0.002) were significantly greater in the luseogliflozin group than in the DPP-4i group.

Table 2 Total and subscale scores of OHA-Q in add-on subgroup
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Among the items that assessed treatment convenience (items 1–9), none of the values were significantly different between the groups (Supplementary Materials Table 2). Similarly, among the items that assessed satisfaction (items 10, 22, and 23), none of the the values were significantly different between the groups. In contrast, among the items that assessed somatic symptoms (items 11–21), scores for item 15 about the tendency to become hungry easily (at 52 weeks), for item 19 about frequent urination (at 24 and 52 weeks), for item 20 about thirst (at 24 and 52 weeks), and for item 21 about discomfort in urination or genital pruritus (at 52 weeks) were significantly lower in the luseogliflozin group than in the DPP-4i group.

Regarding the change in each item score in the add-on subgroup, among the items that consisted of treatment convenience (item 1–9), scores for item 1 about missed dose (at 24 weeks), item 6 about the interval between taking a hypoglycemic agent and a meal (at 24 and 52 weeks), and item 7 about compliance with treatment schedule (at 24 weeks) increased significantly in the luseogliflozin group, but none changed significantly in the DPP-4i group. The change in scores for item 1 about missed dose (at 24 weeks), for item 5 about following the meal schedule (at 24 weeks), for item 6 about the interval between taking a hypoglycemic agent and a meal (at 24 and 52 weeks), for item 7 about compliance with treatment schedule (at 24 weeks), and for item 8 about the change in the number of doses (at 24 weeks) from baseline was significantly higher in the luseogliflozin group than in the DPP-4i group (Supplementary Materials Fig. 1). Among the items that consisted of somatic symptoms (item 11–21), scores for item 11 about rumbling stomach (at 24 weeks), item 14 about for an increase in body weight (at 24 and 52 weeks), item 15 about tendency to become hungry easily (at 24 weeks), item 16 about nausea (at 24 and 52 weeks), and item 17 about bodily swelling (at 24 and 52 weeks) increased significantly, and item 21 about discomfort with urination and genital pruritus (at 24 and 52 weeks) decreased significantly in the luseogliflozin group. However, item 11 about rumbling stomach (at 24 and 52 weeks) and item 12 about diarrhea (at 24 and 52 weeks) increased significantly in the DPP-4i group. The changes in scores for item 14 about for an increase in body weight (at 24 and 52 scores), item 16 about nausea (at 24 weeks), and item 17 about bodily swelling (at 52 weeks) were significantly higher in the luseogliflozin group than in the DPP-4i group, and changes in scores for item 21 about discomfort in urination or genital pruritus (at 24 and 52 weeks) were significantly lower in the luseogliflozin group than in the DPP-4i group. Among the items that assessed satisfaction (items 10, 22, and 23), scores for all items significantly increased in the luseogliflozin group, whereas scores for item 22 about glycemic control (at 24 and 52 weeks) and item 23 about satisfaction with the current agent (at 24 and 52 weeks) increased significantly in the DPP-4i group. No change from baseline was significantly different between the groups.

Stratified analyses were conducted based on baseline BMI and age in the add-on subgroup. In both patients whose BMI was < 25 kg/m2 and those ≥ 25 kg/m2, the total score significantly increased in the luseogliflozin group, but no between-group differences in change in the total scores were detected (Table 3). In patients whose BMI was ≥ 25 kg/m2, somatic symptom and satisfaction scores significantly increased in both the luseogliflozin and DPP-4i groups, and the change in the satisfaction score from baseline to 52 weeks was significantly higher in the luseogliflozin group than in the DPP-4i group. In patients aged < 65 years, the total and subscale scores significantly increased in the luseogliflozin group, while somatic symptoms and satisfaction scores significantly increased in the DPP-4i group; however, no between-group difference in the change in the total OHA-Q and subscale scores was detected (Table 3). In patients whose age was ≥ 65 years, only the satisfaction score significantly increased in the DPP-4i group, and no between-group difference in change in the total and subscale OHA-Q scores was observed.

Table 3 Change in total and subscale scores of OHA-Q from baseline to 52 weeks stratified by baseline BMI and age in add-on subgroup
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Correlations between changes in body weight or HbA1c level and changes in OHA-Q scores were analyzed in the add-on subgroup as post hoc. Changes in HbA1c levels from baseline to 52 weeks did not correlate significantly with changes in the total and subscale OHA-Q scores, whereas changes in body weight were significantly and negatively correlated with changes in the total OHA-Q and treatment convenience scores (Table 4). When stratified by treatment group, change in neither HbA1c level nor body weight was significantly correlated with the total and subscale OHA-Q scores in the luseogliflozin group, but changes in body weight were significantly and negatively correlated with changes in somatic symptoms in the DPP-4i group.

Table 4 Correlation between changes in body weight or HbA1c levels and changes in the OHA-Q scores in add-on subgroup
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Discussion

This sub-analysis of the J-SELECT study compared the effects of a DPP-4i and luseogliflozin on the QOL and treatment satisfaction of patients with type 2 diabetes mellitus. The results showed that the QOL was high in both patients who used luseogliflozin and those using DPP-4is. A previous study reported that the total score of OHA-Q in patients who were using SUs, BGs, αGIs, TZDs, and DPP-4is were 44.6, 42.5, 43.8, 44.7, and 45.9, respectively [11]. Since this previous study had used the OHA-Q version 1, which consisted of 20 items, the total score of OHA-Q version 2 in the luseogliflozin group in this study cannot be directly compared with the scores of the previous study. However, considering that the total score of OHA-Q version 1 in patients with DPP-4is was as high as or even higher than that with other OHAs, and the total scores of OHA-Q version 2 in the luseogliflozin group and the DPP-4i group were comparable in this study, QOL and treatment satisfaction of patients who used luseogliflozin or DPP-4is in this study were comparable to or even higher than for those who used conventional OHAs.

In the drug-naïve patients, who newly initiated the luseogliflozin or DPP-4i after the baseline, subscale 1 “treatment convenience” and subscale 3 “satisfaction” scores did not differ between the groups. This may be because the two tablets had similar size, and the usage was once daily. In contrast, total score and subscale 2 “somatic symptom” score were significantly higher in the DPP-4i group than in the luseogliflozin group at 52 weeks. This may reflect the results that among the items that comprise the somatic symptom, item 15 asking about the tendency to become hungry easily, 19 asking about frequent urination, 20 asking about thirst, and 21 asking about discomfort with urination or genital pruritus were significantly lower in the luseogliflozin group than in the DPP-4i group. Since these were well-known side effects of SGLT2is, physicians should pay attention to such side effects to maintain the patients’ QOL when drug-naïve patients initiate the SGLT2is.

In contrast, in patients who were treated with OHAs other than SGLT2is and DPP-4is at baseline, when luseogliflozin or the DPP-4is were added, total score and treatment convenience score significantly increased in the luseogliflozin compared with the DPP-4i group. This may reflect the results that among the items that comprise the treatment convenience, item 1 asking about missed dose, item 5 asking about following the meal schedule, item 6 asking about the interval between taking the agent and a meal, item 7 asking about compliance with treatment schedule, and item 8 asking about the number of doses significantly increased in the luseogliflozin group compared with the DPP-4i group. However, changes in somatic symptom scores did not differ between the groups. This may be because although the question enquiring about an increase in body weight and item 17 enquiring about bodily swelling significantly increased in the luseogliflozin group, and these were well-known beneficial effects of SGLT2i, item 21 regarding discomfort with urination or genital pruritus significantly decreased, and item 19 about frequent urination and item 20 about thirst numerically decreased (not significantly) in the luseogliflozin group, and these were well-known side effects of SGLT2i. Again, physicians should pay attention to such side effects to maintain or improve the patients’ QOL when SGTL2is are added on to the other OHAs.

Regarding the safety, scores for item 18, which enquired about hypoglycemia, did not change in the luseogliflozin or DPP-4i group, and no between-group difference in change was observed. Both SGLT2is and DPP-4is are known to have a relatively low risk of hypoglycemia; indeed, only 0.3% and 1.0% of patients in the luseogliflozin and DPP-4i groups, respectively, reported (non-serious) hypoglycemia in this study [14]; however, scores for item 18 did not change in either group. One reason for this might be that the enrolled patients in this study were drug-naïve or treated with antidiabetic agents other than SGLT2is and DPP-4is, but few among those treated with antidiabetic agents other than SGLT2is and DPP-4is had used insulin, Sus or glinide at enrollment [14]. Therefore, the possibility of hypoglycemia was small in the enrolled patients, and the absence of hypoglycemia did not improve their QOL. In addition, since DPP-4is are incretin-based agents, the occurrence of gastrointestinal symptoms is a concern, but scores for item 11, enquiring about rumbling stomach, item 12 about diarrhea, item 13 about constipation, and item 16 about nausea did not differ between the groups, except for the change in scores for item 16 at 24 weeks. These results confirmed the safety profile of both luseogliflozin and DPP-4is. Conversely, in terms of efficacy, scores for items 22 (glycemic control) and 23 (satisfaction with the current agent) significantly increased in both groups, and no between-group difference was observed. These results seemed to be consistent with the results that the decrease in HbA1c level was comparable between the groups (adjusted mean change from baseline to 52 weeks were − 0.7 ± 0.0% and − 0.6 ± 0.0% in the luseogliflozin group and the DPP-4i group, respectively; p = 0.18 for between-group comparison) [14]. Scores for item 14, which enquired about an increase in body weight, significantly increased only in the luseogliflozin group, and a significant between-group difference in this change was observed. It is well known that SGLT2is reduce body weight [15], whereas DPP-4is have a neutral effect or cause a modest increase [16, 17]. Our previous paper also showed that body weight significantly decreased in the luseogliflozin group compared with that in the DPP-4i group (adjusted mean percent changes from baseline to 52 weeks were − 4.0 ± 0.3% and − 0.7 ± 0.3% in the luseogliflozin group and DPP-4i group, respectively; p < 0.001 for between-group comparison) [14]. The results pertaining to the QOL of patients were consistent with those of efficacy and safety.

A previous study using dapagliflozin showed a significant correlation between body weight reduction and treatment satisfaction, indicating that a greater reduction in body weight resulted in higher satisfaction [4]. However, the post-hoc analysis in this study did not show a correlation between the degree of body weight reduction and QOL and treatment satisfaction in the luseogliflozin group. One reason might be that the previous study investigated patients’ QOL and treatment satisfaction 14 weeks after the initiation of dapagliflozin, whereas this study assessed patients’ QOL and treatment satisfaction 24 and 52 weeks after the initiation of luseogliflozin or DPP-4is. This might be explained by the “adaptation hypothesis” in economics; if income increases, happiness tentatively increases, but because the “baseline level” of happiness also increases, and humans quickly become accustomed to the situation, happiness returns to the original level [18]. One report showed that the effect of income increases on happiness remained at only 42% 4 years later compared to 1 year after the income increase [19]. Similarly, at the initiation/add-on of SGLT2is, patients may feel satisfied because of body weight reduction but gradually become accustomed to it, resulting in a reduction in their satisfaction or QOL. Since body weight reduction is generally observed approximately 4 weeks after the administration of SGLT2is, assessment of the QOL and treatment satisfaction at an earlier stage might be required.

Although our previous report demonstrated the overall and multiple aspects of efficacy of luseogliflozin compared with DPP-4is in the mid/long term, regardless of BMI or age [14], this subanalysis regarding the patients’ QOL and treatment satisfaction showed that both luseogliflozin and DPP-4is improved the QOL and treatment satisfaction in patients with BMI of ≥ 25 kg/m2) or patients aged < 65 years. This may be because the number of patients whose BMI was < 25 kg/m2 or age was ≥ 65 years was too small, and the statistical power was not adequate to assess the intragroup improvement or between-group difference. Further investigation is required to assess the effect of BMI or age on patients’ QOL and treatment satisfaction after the initiation of luseogliflozin or DPP-4is.

The authors note several possible limitations in this study. First, this was an open-label study for both patients and physicians. In addition, this sub-analysis focused on patients’ QOL and treatment satisfaction, which were determined based on patient responses. This open-label nature and subjective endpoint may have created bias in this study. Second, this study was conducted only in Japan, and all patients were Japanese. Since DPP-4is are more effective in the Asian population [7], the generalizability of the results of this study to other countries or patients of other ethnicities should be considered. Further investigations with patients of other ethnicities should be conducted. Third, luseogliflozin was launched in Japan and several Asian countries but not in the US or Europe. Therefore, the results of this study may not be directly applicable to other countries. Effects of other SGLT2is, which were available in the US or Europe, on patients’ QOL and treatment satisfaction should be further investigated in the future. Also, although DPP-4is are the most frequently prescribed OHAs in Japan [8,9,10], and the prescription rate of DPP-4is was relatively high in several Asian countries [20], it was relatively low in the US and European countries [21, 22]. This should be considered when interpreting the results of this study. Fourth, the OHA-Q is used to assess the QOL and treatment satisfaction of patients using OHAs. Although this study registered patients with type 2 diabetes mellitus who were drug-naïve or treated with antidiabetic agents other than SGLT2is and DPP-4is, patients’ QOL and treatment satisfaction at baseline could not be assessed in drug-naïve patients. Sixth, stratified analysis with BMI used 25 kg/m2 as threshold. This was because the Japan Society for the Study of Obesity defined obesity as BMI ≥ 25 kg/m2; however, the definition of obesity varies between countries. Further analysis should consider different definitions of obesity, which are applicable worldwide.

Conclusion

In conclusion, this study showed that QOL and treatment satisfaction were high in both patients who used luseogliflozin and those who used DPP-4is. Because QOL regarding somatic symptoms was lower in the luseogliflozin group than in the DPP-4i group, physicians should pay attention to side effects of SGLT2is, such as hunger, frequent urination, thirst, discomfort urinating, or genital pruritus, to maintain the patients’ QOL when SGLT2is are initiated or added on. In contrast, if luseogliflozin or DPP-4is were added on to previously used OHAs, patients’ QOL increased in the luseogliflozin group compared with the DPP-4i group. Furthermore, satisfaction increased in patients with BMI ≥ 25 kg/m2 who received luseogliflozin. The QOL related to safety or glycemic control was comparable between the groups. The results of this study suggest the importance of considering patients’ QOL and treatment satisfaction when selecting SGLT2is or DPP-4is.