AIMS:This study evaluated the efficacy and safety of anagliptin added to metformin and empagliflozin in patients with type 2 diabetes (T2DM) inadequately controlled on dual therapy. METHODS:In this multicenter, randomized, double-blind, placebo-controlled phase 3 trial, patients with T2DM (HbA1c 7.0-11.0 %) on metformin (≥1000 mg/day) and empagliflozin (25 mg/day) were randomized 1:1 to anagliptin (100 mg twice daily) or placebo for 24 weeks, followed by a 28-week open-label extension. The primary endpoint was HbA1c change from baseline to week 24. RESULTS:Of 200 randomized patients, 197 were analyzed (baseline HbA1c 7.76 %). At week 24, the least-squares mean HbA1c change was -0.83 % with anagliptin versus -0.03 % with placebo (difference -0.80 %; 95 % CI - 0.95 to - 0.64; P < 0.0001). The least-squares mean change in HOMA-β was + 10.45 versus -6.02 with placebo (between-group difference 16.46; P = 0.0003). Adverse events were similar between groups, with no severe hypoglycemia or deaths. CONCLUSIONS:In this first placebo-controlled trial evaluating DPP-4 inhibitor addition to maximally dosed empagliflozin (25 mg) plus metformin, anagliptin significantly improved glycemic control and β-cell function with a favorable safety profile, supporting this triple combination as an effective intensification strategy.

AIMS:To assess the efficacy and safety of alpha-lipoic acid (ALA) and pregabalin, both as mono and combination therapy, for treating painful diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus, with the hypothesis that pregabalin monotherapy is non-inferior to combination therapy. MATERIALS AND METHODS:A phase 4 randomized, active-controlled, open-label, multicentre trial was conducted over 12 weeks to investigate changes in visual analogue scale (VAS) pain scores from baseline as a primary efficacy endpoint. A total of 151 eligible subjects were randomly assigned to ALA (480 mg/day), pregabalin (150 mg/day), and combination groups in a 1:1:1 ratio. RESULTS:The pregabalin monotherapy group showed a VAS change of -19.73 ± 18.94 mm, while the combination group showed -23.28 ± 18.15 mm at Week 12. The least square mean (LSM) difference between the two groups was 3.46 mm (95% CI: [-4.94, 11.87]), demonstrating that pregabalin monotherapy is non-inferior to combination therapy. Safety analysis revealed no significant differences across treatment groups. Cluster analysis revealed statistically significant differences in VAS scores between the pregabalin monotherapy and combination therapy groups at 12 weeks in cluster 1, characterized by a relatively shorter duration of DPN, and the LSM difference between both groups was 14.79 mm [4.59, 24.99] (p = 0.0055). CONCLUSIONS:The pregabalin monotherapy demonstrated non-inferiority compared to the combination therapy in alleviating DPN pain. Cluster analysis supported the identification of patient groups where combination therapy could be more effective, but future comprehensive studies are required for further verification. TRIAL REGISTRATION:ClinicalTrials.gov, NCT04846673.

Introduction and Objective: Type 2 diabetes mellitus (T2DM) patients inadequately controlled with metformin and empagliflozin require additional therapies to improve glycemic control. This study evaluated the efficacy and safety of anagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, as add-on therapy to metformin and empagliflozin. Methods: In this multicenter, randomized, double-blind, placebo-controlled phase III trial, we enrolled patients with T2DM inadequately controlled (HbA1c 7.0-11.0%) on metformin (≥1000 mg/day) and empagliflozin (25 mg/day). Patients were randomized 1:1 to receive anagliptin (100 mg twice daily) or placebo for 24 weeks, followed by a 28-week open-label extension. The primary endpoint was change in HbA1c from baseline to week 24. Results: Of 200 randomized patients (n=97 anagliptin, n=100 placebo; mean age 58.6 years; baseline HbA1c 7.76%), 197 completed primary analysis. At week 24, HbA1c decreased 0.83% in anagliptin group versus 0.03% in placebo (difference -0.80%; 95% CI -0.95 to -0.64; P<0.0001). More patients achieved HbA1c ≤7.0% (60.8% vs. 18.0%; P<0.0001) and ≤6.5% (25.8% vs. 3.0%; P<0.0001). Fasting plasma glucose decreased 11.1 mg/dL in anagliptin versus increased 5.75 mg/dL in placebo (P<0.0001). HOMA-β improved: +10.45 versus -6.02 (P=0.0003). During open-label extension, placebo-treated patients switching to anagliptin achieved similar HbA1c at week 52 (anagliptin: 7.14% vs. original placebo: 7.17%; P=0.60), while anagliptin group maintained durable efficacy (change from baseline: -0.59%). Adverse events showed no significant difference between groups over 52 weeks (anagliptin 20.2% vs. placebo 29.0%; P=0.15). No severe hypoglycemia or deaths occurred. Conclusion: Anagliptin as add-on therapy to metformin and empagliflozin 25 mg significantly improves glycemic control and β-cell function with a favorable safety profile in T2DM patients inadequately controlled on dual therapy. Disclosure J. Moon: None. S. Park: Employee; Current; JW Pharmaceutical Corporation. J. Won: None. J. Kang: None. K. Han: None. J. Yu: None. C. Park: None.

AIMS:Evogliptin, a dipeptidyl peptidase-4 inhibitor with a glucose-dependent mechanism of action, is widely used as a monotherapy or in combination with other agents. However, observational studies in routine clinical settings remain limited. This study aimed to evaluate the effectiveness and safety of evogliptin in combination with other antidiabetic agents frequently used in clinical practice. METHODS:This study was conducted in 51 hospitals in South Korea. We evaluated evogliptin in three groups: the evogliptin add-on, evogliptin-switching, and initial combination groups. The primary endpoint was the change in haemoglobin A1c (HbA1c) levels (%) from baseline to 12 weeks. The change in HbA1c (%) levels from baseline to 24 weeks was a secondary endpoint in the extended study. Proportions of patients achieving the HbA1c target, changes in fasting and postprandial glucose levels, and safety endpoints were also evaluated. Between-group comparisons were performed between the add-on and initial combination groups. RESULTS:In the 1596 patients of the effectiveness set, the mean changes in HbA1c levels at 12 weeks were -0.8% ± 1.2%, -0.3% ± 0.8% and -1.9% ± 1.4% for the evogliptin add-on, evogliptin-switching and initial combination groups, respectively. Among the 1920 patients in the safety set, 23 experienced adverse drug reactions, and there was no significant difference among the three groups. CONCLUSION:Evogliptin reduces blood glucose levels and is well-tolerated when used as an add-on, as a switch from other dipeptidyl peptidase 4 inhibitors, or as part of an initial combination therapy in patients with type 2 diabetes mellitus.

BACKGROUND:Type 2 diabetes mellitus (T2DM) is a progressive, multi-organ disorder that often requires intensive combination therapy. This Phase III, randomised, double-blind, placebo-controlled study evaluated the efficacy and safety of two fixed-dose combinations (FDCs) of sitagliptin 100 mg with empagliflozin 10 mg (DW1026C1) or empagliflozin 25 mg (DW1026C2) as add-on therapy for patients with inadequately controlled T2DM. METHODS:Two hundred thirty adults with T2DM inadequately controlled by metformin (≥ 1000 mg/day) and sitagliptin (100 mg) were 1:1:1 randomised to receive DW1026C1 (E10 group, n = 77), DW1026C2 (E25 group, n = 76), or a placebo (n = 77). Treatment was administered for 24 weeks, followed by a 28-week extension period. The primary endpoint was the change in HbA1c from baseline to Week 24. RESULTS:Baseline characteristics were similar among groups. At Week 24, both active treatments demonstrated statistically significant HbA1c reductions versus the placebo. The least square mean differences [95% CI] versus the placebo were -0.54% [-0.78, -0.29] for E10 group and -0.61% [-0.85, -0.36] for E25 group (both p < 0.0001). Fasting plasma glucose (FPG), insulin resistance, body weight, systolic blood pressure, albumin-creatinine ratio and high-density lipoprotein cholesterol also improved in the active groups. Reductions in HbA1c, FPG and insulin resistance were sustained in Week 52. Safety profiles were favourable with adverse events similar in frequency and no increased hypoglycaemia risk. CONCLUSION:Sitagliptin/empagliflozin FDC doses achieved improvements in glycaemic control at 24 weeks, which was maintained through 52 weeks. These benefits were accompanied by a favourable safety profile, including a very low risk of hypoglycaemia. TRIAL REGISTRATION:NCT07076056.

ABSTRACT Aim This study aimed to evaluate the prevalence, clinical characteristics, and factors associated with cardiovascular autonomic neuropathy (CAN) in Korean individuals with long‐standing type 2 diabetes mellitus (T2DM). Methods A total of 876 participants with long‐standing T2DM were enrolled in this multicenter cross‐sectional study. CAN was evaluated using standard cardiovascular autonomic reflex tests (CARTs) and corrected QT interval (QTc), with additional heart rate variability (HRV) analysis. CAN severity was classified as early, definite, or severe. Multivariable logistic regression analysis was performed to identify factors independently associated with CAN. Results CAN was detected in 88.4% of participants. Individuals with CAN showed reduced HRV indices and prolonged QTc intervals. Multivariable analysis revealed advanced age (OR = 1.062; 95% CI: 1.035–1.091; p < 0.0001) and higher systolic blood pressure (OR = 1.036; 95% CI: 1.022–1.051; p < 0.0001) as factors independently associated with CAN. Conclusion CAN is highly prevalent among Korean individuals with long‐standing T2DM. Older age and elevated systolic blood pressure were independently associated with CAN, highlighting the importance of routine CAN screening and careful blood pressure management.

BACKGRUOUND:This study assessed the efficacy and safety of HD-6277, a novel oral G protein-coupled receptor 40 (GPR40) agonist in adults with inadequate control of type 2 diabetes mellitus (T2DM). METHODS:This double-blind, randomized, placebo-controlled phase 2 trial recruited 112 individuals aged 18-75 years with T2DM and glycosylated hemoglobin (HbA1c) levels between 7.0% and 10.0% while on diet and exercise alone for at least 8 weeks before screening. Parallel-group randomized trials of HD-6277 (50 and 100 mg groups vs. placebo) were conducted for 12 weeks. The primary outcome was the change in HbA1c levels from baseline to week 12. Secondary outcomes included changes in HbA1c, fasting plasma glucose (FPG), postprandial glucose, insulin, glycoalbumin, and C-peptide at weeks 4, 8, and 12. RESULTS:At week 12, HD-6277 at 50 and 100 mg demonstrated statistically significant reductions in HbA1c compared to placebo, with least square (LS) mean differences of -0.73% (95% confidence interval [CI], -1.11 to -0.35; P=0.0002) and -0.85% (95% CI, -1.21 to -0.50; P<0.0001), respectively. Both doses also produced clinically meaningful reductions in FPG. Additionally, HD- 6277 at 100 mg significantly increased the insulinogenic index compared to placebo, with an LS mean difference of 1.91 (95% CI, 0.34 to 3.48; P=0.0175). No clinically relevant treatment-related adverse events were observed. CONCLUSION:HD-6277 at 50 and 100 mg improved glycemic control and was well-tolerated in adults with T2DM inadequately managed with diet and exercise. GPR40 agonists may offer a promising new therapeutic option for T2DM.

AIMS:To assess the efficacy and safety of sarpogrelate (300 mg) for symptom improvement in patients having peripheral arterial disease (PAD) and/or being at risk of PAD in clinical practice using the Peripheral Artery Questionnaire (PAQ). BACKGROUND:Symptomatic changes with antiplatelets in patients with PAD are limited. OBJECTIVE:To determine the effect and safety of sarpogrelate on the PAQ at 24 weeks from baseline. METHODS:A total of 1003 patients having PAD and/or being at risk of PAD from 17 tertiary hospitals in South Korea who were treated with sarpogrelate, were enrolled in this study. PAQs were collected at baseline and at 12 and 24 weeks, together with physical examination and vital signs measurements. Lifestyle pattern was also investigated. RESULTS:The average PAQ Summary Score in the efficacy evaluation analysis group significantly improved from 62.9 ± 23.7 at baseline to 68.9 ± 21.7 at 24 weeks (P<0.0001). Physical limitation items significantly improved from 69.5 ± 30.0 at baseline to 72.9 ± 28.3 after 24 weeks (P=0.0011). Symptom stability also significantly improved from 52.1 ± 21.6 at baseline to 63.6 ± 22.9 after 24 weeks (P<0.0001). Symptoms, treatment satisfaction, quality of life, and social limitation domains all improved after treatment. A total of 201 patients reported adverse events (20.0%), not directly associated with treatment. CONCLUSION:Treatment with 300 mg (orally) of sarpogrelate demonstrated statistically significant improvements in all domains and for the summary score of the PAQ at 24 weeks, it gave good results in terms of safety. Sarpogrelate may be helpful in reducing symptoms related to PAD.

AIM:This study evaluated the efficacy and safety of empagliflozin 10 and 25 mg compared to placebo as add-on treatment for people with type 2 diabetes mellitus (T2DM) uncontrolled after ≥8 weeks of treatment with metformin and sitagliptin. MATERIALS AND METHODS:A randomised, double-blind, multicentre, therapeutic confirmatory, phase 3 clinical trial was conducted in 172 patients with T2DM. Participants with glycosylated haemoglobin (HbA1c) levels 7%-10% receiving sitagliptin and metformin were randomised 1:1:1 to empagliflozin 10 mg, empagliflozin 25 mg, or placebo. The primary endpoint was the change in HbA1c from baseline to week 24. RESULTS:After 24 weeks of treatment, HbA1c levels were significantly decreased in the empagliflozin 10 and 25 mg group versus the placebo group; the adjusted mean differences with empagliflozin 10 and 25 mg versus placebo were -0.7% (95% CI -1.0, -0.4; p <.0001) and -0.8% (95% CI -1.1, -0.5; p <.0001), respectively. Fasting plasma glucose levels were also significantly decreased in both empagliflozin groups compared to the placebo group (both p <.0001). More patients reached HbA1c <7% or <6.5% after 24 weeks in the empagliflozin 10 and 25 mg groups versus the placebo group (both p <.05). Efficacy was maintained in the empagliflozin groups during a 28-week extension period. Empagliflozin add-on was associated with improvements in albuminuria and body weight. The incidence of adverse events was similar across groups; add-on empagliflozin was well tolerated. CONCLUSIONS:These results suggest that coadministration of empagliflozin safely improves glycemic control in Korean patients with T2DM uncontrolled by sitagliptin and metformin.

AIMS:This post hoc analysis assessed the efficacy and safety data in tirzepatide-treated Korean patients with type 2 diabetes (T2D). MATERIALS AND METHODS:Data specifically from Korean patients treated with tirzepatide 5, 10, or 15 mg in the multicentre, randomised, open-label, parallel-group, phase 3 trials SURPASS-AP-Combo and SURPASS-3 were extracted and analysed. Efficacy (change from baseline in glycated haemoglobin [HbA1c] and body weight, and proportions of participants achieving HbA1c and body weight targets) and safety endpoints were evaluated at week 40 (SURPASS-AP Combo) and week 52 (SURPASS-3). RESULTS:In the SURPASS-AP-Combo and SURPASS-3, 79 of 687 and 27 of 1079 tirzepatide recipients, respectively, were Korean. In Korean participants in SURPASS-AP-Combo across all tirzepatide doses, least squares mean (LSM) HbA1c was reduced from baseline by 2.75% to 3.25% and HbA1c targets of <7.0% and ≤6.5% were achieved by 84.6% to 100% at week 40; LSM body weight reductions of -6.8% to -10.9% from baseline were achieved. The composite endpoint of HbA1c ≤6.5% without body weight gain or clinically significant documented symptomatic or severe hypoglycaemia was achieved by 69.2% to 85.2% of tirzepatide recipients. Findings were similar in Korean participants of SURPASS-3. The safety profile of tirzepatide in Korean participants was generally consistent with that in the overall SURPASS-AP-Combo and SURPASS-3 populations. CONCLUSIONS:Consistent with the overall results of the SURPASS-AP-Combo and SURPASS-3 trials, this post hoc subgroup analysis found clinically meaningful reductions in HbA1c and body weight after treatment periods of 40 to 52 weeks in Koreans with T2D treated with tirzepatide.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus that encompasses a heterogeneous group of conditions with diverse clinical manifestations. Despite its prevalence, no universally established classification or treatment approach is currently available. Recent findings have underscored the role of systemic inflammation, oxidative stress, and neurochemical imbalances in shaping DPN phenotypes, emphasizing the need for phenotype-specific diagnostic and therapeutic approaches. Advanced diagnostic techniques, including magnetic resonance imaging-based neuroimaging and quantitative sensory testing, are emerging as tools for phenotypic characterization. Therapeutic interventions are moving toward precision medicine, with targeted pharmacological and non-pharmacological strategies tailored to specific clinical presentations. Innovations such as digital health platforms, regenerative therapies, and combinatorial pharmacotherapy are promising for addressing primary neuropathic pain and its associated complications. This review synthesizes the current evidence on DPN phenotypes (painful, painless, and mixed forms), their underlying pathophysiological mechanisms, and the efficacy of treatment approaches. A framework for optimizing management strategies is also proposed. By leveraging novel insights into sensory phenotypes and treatment responsiveness, clinicians can adopt DPN phenotype-based treatment models to optimize patient care, improve treatment outcomes, reduce the substantial disease burden, and enhance patient quality of life.

BACKGRUOUND:This study investigated the efficacy and safety of pioglitazone 30 mg/day add-on to inadequately controlled type 2 diabetes mellitus (T2DM) patients with treatment of dapagliflozin and metformin. METHODS:In this multicenter (34 sites), double-blind, randomized, phase 3 study, patients with T2DM with an inadequately controlled glycosylated hemoglobin (HbA1c) over 7.0% to treatment with dapagliflozin (10 mg/day) and metformin (≥1,000 mg/day) were randomized to receive additional pioglitazone 30 mg/day (n=124) or placebo (n=122) for 24 weeks. The primary outcome was the mean change of HbA1c from baseline to 24 weeks treatment. The efficacy and safety were evaluated with open label extension period, switching placebo to pioglitazone 30 mg/day at 48 weeks (ClinicalTrials.gov identifier: NCT05296044). RESULTS:The HbA1c after 24 weeks treatment reduced from 7.8%±0.8% to 7.0%±0.6% (P<0.0001). The proportions of patients who achieved HbA1c less than 7.0% at 24 weeks were significantly higher in pioglitazone add-on group (51.61% in pioglitazone vs. 22.95% in placebo, P<0.0001), or less than 6.5% at 24 weeks (21.77% in pioglitazone vs. 2.46% in placebo, P<0.0001). Body weight gain was 2.0 kg at 24 weeks with pioglitazone 30 mg/day and -0.6 kg at 24 weeks with placebo. CONCLUSION:Addition of pioglitazone 30 mg/day to T2DM patients who did not reach the target HbA1c (≤7%) with treatment of dapagliflozin 10 mg/day and metformin over 1,000 mg/day showed effective glucose lowering efficacy without significant hypoglycemia and good tolerability with low prevalence of edema in spite of modest weight gain.

BACKGROUND:Cardiovascular autonomic neuropathy (CAN) is a frequently underdiagnosed complication of diabetes mellitus that contributes to increased mortality and morbidity rates. This multicenter study investigated the epidemiology and clinical characteristics of CAN in patients with long-term diabetes. METHODS:Retrospective data were collected from 884 individuals with diabetes who were assessed for CAN across eight hospitals in Korea. CAN was diagnosed using electrocardiography and cardiovascular autonomic function tests, including the heart rate-corrected QT interval and Ewing's method. This study evaluated the clinical characteristics, cardiovascular autonomic nerve function test results, and risk factors associated with CAN. RESULTS:Among the 884 patients, 778 (88%) were diagnosed with CAN (DCAN), while 106 (12%) were not (non-DCAN). Individuals with DCAN were older, had a longer duration of diabetes, and had higher creatinine levels. The DCAN group showed decreased time and frequency parameters of heart rate variability (HRV). A multiple logistic regression analysis revealed that a longer diabetes duration, older age, and higher creatinine level were significant risk factors for CAN. CONCLUSION:CAN was associated with advanced age, a longer duration of diabetes, higher creatinine levels, and lower time and frequency HRV parameters.

BACKGROUND:The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. METHODS:This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). CONCLUSION:This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

AIMS:To evaluate the long-term safety and efficacy of enavogliflozin monotherapy (0.3 mg/day) in individuals with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS:Following a 24-week randomized, double-blind treatment period with enavogliflozin 0.3 mg/day (n = 77) or placebo (n = 69), consenting participants received enavogliflozin 0.3 mg/day for an additional 28 weeks during an open-label extension (OLE) period. The safety and efficacy of enavogliflozin were assessed at Week 52. RESULTS:A total of 37 participants continued enavogliflozin (maintenance group), and 26 participants switched from placebo to enavogliflozin (switch group). No additional adverse drug reactions related to enavogliflozin were observed during the OLE period. At Week 52, glycated haemoglobin (HbA1c) and fasting plasma glucose were significantly lower than at the baseline, by 0.9% and 24.9 mg/dL, respectively, in the maintenance group (p < 0.0001 for both), and by 0.7% and 18.0 mg/dL, respectively, in the switch group (p < 0.0001 and p = 0.002). The proportions of participants reaching HbA1c 7.0% (53 mmol/mol) at Week 52 were 69.4% in the maintenance group and 65.4% in the switch group. A significant increase in urine glucose-to-creatinine ratio was observed at Week 52, by 84.9 g/g and 67.1 g/g in the maintenance and switch groups, respectively (p < 0.0001 for both). Body weight in both groups decreased significantly (p < 0.0001) from baseline to Week 52, by 3.5 kg and 3.8 kg in the maintenance and switch groups, respectively. CONCLUSIONS:Enavogliflozin 0.3 mg monotherapy provides long-term glycaemic control in T2DM and is safe and well tolerated during a 52-week treatment period.

Epidemiological evidence has shown that diabetes is associated with overt heart failure (HF) and worse clinical outcomes. However, the presence of a distinct primary diabetic cardiomyopathy (DCM) has not been easy to prove because the association between diabetes and HF is confounded by hypertension, obesity, microvascular dysfunction, and autonomic neuropathy. In addition, the molecular mechanisms underlying DCM are not yet fully understood, DCM usually remains asymptomatic in the early stage, and no specific biomarkers have been identified. Nonetheless, several mechanistic associations at the systemic, cardiac, and cellular/molecular levels explain different aspects of myocardial dysfunction, including impaired cardiac relaxation, compliance, and contractility. In this review, we focus on recent clinical and preclinical advances in our understanding of the molecular mechanisms of DCM and the role of anti-hyperglycemic agents in preventing DCM beyond their glucose lowering effect.

Abstract Background The target blood pressure (BP) value is unclear for diabetic kidney disease (DKD). Therefore, we aimed to evaluate the effect of strict BP control or ‘on treatment’ BP on clinical outcomes in patients with DKD. Methods A post-hoc analysis of the prespecified secondary outcomes of the FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC) trial, a randomized multicenter double-blind phase III trial. Eligible patients were aged ≥ 19 years with DKD. We assigned 341 participants with DKD to BP control strategy (standard-systolic BP [SBP] < 140 mmHg versus strict-SBP < 130 mmHg). The outcome was the occurrence of cardiovascular events and renal events. Separate analyses were performed to compared the risk of outcome according to achieved average BP levels. Results A total of 341 participants were included in the analysis. Over a median follow-up of 2.8 years, cardiovascular/renal events were observed in 25 (7.3%) participants. Mean (SD) SBPs in the standard and strict BP control group were 140.2 (11.6) and 140.2 (11.9) mmHg, respectively. The strict BP control group did not show significantly reduced risk of cardiovascular/renal events (HR 1.32; 95% CI 0.60–2.92]). In the post-hoc analyses using achieved BP, achieved average SBP of 130–139 mmHg resulted in reduced risk of cardiovascular/renal events (HR 0.15; 95% CI 0.03–0.67) compared to achieved average SBP ≥ 140 mmHg, whereas further reduction in achieved average SBP < 130 mmHg did not impart additional benefits. Conclusion In patients with DKD, targeting a SBP of less than 130 mmHg, as compared with less than 140 mmHg, did not reduce the rate of a composite of cardiovascular and renal events. Achieved SBP of 130–139 mmHg was associated with a decreased risk for the primary outcome in patients with DKD. Trial registration ClinicalTirals.gov Identifier: NCT02620306, registered December 3, 2015. ( https://clinicaltrials.gov/study/NCT02620306 ).