Doo Man Kim

Efficacy and Safety of Lobeglitazone Monotherapy in Patients with Type 2 Diabetes Mellitus over 24-Weeks: A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo Controlled Trial

Objective The aim of this study was to assess the glucose-lowering and lipid-modifying effects, and safety profile of lobeglitazone, a novel peroxisome proliferator-activated receptor- γ agonist, compared to placebo as a monotherapy in patients with type 2 diabetes. Research Design and Methods In this 24-week, multicenter, randomized, double-blind, parallel-group, placebo controlled study, 173 patients were randomly assigned (a 2∶1 ratio) to lobeglitazone 0.5 mg (nu200a=u200a115) or matching placebo (nu200a=u200a58) orally once daily. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to the end of treatment. The secondary endpoints included various glycemic parameters, lipid parameters and safety profile (ClinicalTrials.gov number NCT01001611). Results At 24 weeks, a significant reduction in HbA1c was observed with lobeglitazone versus placebo (−0.44% vs 0.16%, mean difference −0.6%, p<0.0001). The goal of HbA1c <7% was achieved significantly more in the lobeglitazone group compared to the placebo group (44% vs 12%, p<0.0001). Markers of insulin resistance were also improved in the lobeglitazone group. In addition, lobeglitazone treatment significantly improved triglycerides, high density lipoprotein cholesterol, small dense low density lipoprotein cholesterol, free fatty acid, and apolipoprotein-B/CIII compared to placebo (p<0.01, respectively). More weight gain was observed in the lobeglitazone group than the placebo group (0.89 kg vs – 0.63 kg, mean difference 1.52 kg, p<0.0001). The safety profile was comparable between the two groups and lobeglitazone was well tolerated. Conclusions Lobeglitazone 0.5 mg showed a favorable balance in the efficacy and safety profile. The results support a potential role of lobeglitazone in treating type 2 diabetes. Trial Registration Clinicaltrials.gov NCT01001611

Safety and efficacy of lobeglitazone monotherapy in patients with type 2 diabetes mellitus over 52 weeks: An open-label extension study

We aimed to assess the safety and efficacy of lobeglitazone in patients with type 2 diabetes over 52 weeks through 28-week extension study. Clinical benefits in terms of glycemic and lipid control were maintained for 52 weeks. Lobeglitazone showed a favorable balance of efficacy and safety during the extension study.

A randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of anagliptin in drug-naïve patients with type 2 diabetes

The aim of this study was to evaluate the efficacy and safety of anagliptin in drug-naïve patients with type 2 diabetes in a double-blind randomized placebo-controlled study. A total of 109 patients were randomized to 100 mg (n=37) or 200 mg (n=33) anagliptin twice daily or placebo (n=39). The primary objective was to alter HbA1c levels from baseline at a 24-week endpoint. The overall baseline mean age and body mass index were 56.20 ± 9.77 years and 25.01 ± 2.97 kg/m(2), respectively, and the HbA1c level was of 7.14 ± 0.69 %. Anagliptin at 100 mg and 200 mg produced significant reductions in HbA1c (-0.50 ± 0.45 % and -0.51 ± 0.55%, respectively), and the placebo treatment resulted in an increase in HbA1c by 0.23 ± 0.62 %. Both doses of anagliptin produced significant decreases in fasting plasma glucose (-0.53 ± 1.25 mmol/L and -0.72 ± 1.25 mmol/L, respectively) and the proinsulin/insulin ratio (-0.04 ± 0.15 and -0.07 ± 0.18, respectively) compared with placebo. No meaningful body weight changes from baseline were observed in three groups. Plasma dipeptidyl peptidase (DPP)-4 activity was significantly inhibited after 24 weeks of anagliptin treatment, and >75% and >90% inhibitions were observed during the meal tolerance tests with 100 mg and 200 mg anagliptin, respectively. The incidences of adverse or serious adverse events were similar among the three study groups. Twice-daily anagliptin therapy effectively inhibited DPP-4 activity and improved glycemic control and was well-tolerated in patients with type 2 diabetes.

Visceral adiposity and skeletal muscle mass are independently and synergistically associated with left ventricular structure and function: The Korean Genome and Epidemiology Study

BACKGROUNDnObesity and low muscle mass may coexist as age-related changes in body composition. We aimed to investigate the effect of visceral adiposity and skeletal muscle mass on left ventricular (LV) structure and function in the general population.nnnMETHODSnA total of 1941 participants without known cardiovascular disease were enrolled from the Korean Genome and Epidemiology Study. Visceral fat area (VFA) was assessed by computed tomography. Appendicular skeletal muscle mass (ASM) was estimated by dual-energy X-ray absorptiometry and was used as a percentage of body weight (ASM/Wt). LV structure and function were assessed by tissue Doppler imaging (TDI) echocardiography.nnnRESULTSnAcross VFA tertiles, ASM increased, but ASM/Wt decreased (all P<0.001). In multivariate models adjusted for conventional cardiovascular risk factors, LV mass index and LV diastolic parameters, such as left atrial dimension, TDI Ea velocity, and E/Ea ratio, were significantly impaired as VFA increased. On the other hand, an increase in ASM/Wt was associated with a decrease in LV mass index and improvement of LV diastolic parameters. With regard to LV mass index and TDI Ea velocity, VFA and ASM/Wt showed synergistic effects (all P interaction<0.05). When both VFA and ASM/Wt were simultaneously included in the same model, both remained independent predictors of LV mass index and TDI Ea velocity.nnnCONCLUSIONSnMore visceral fat and less muscle mass are independently and synergistically associated with an increase in LV mass index and impairment of LV diastolic parameters. Further research is needed to explore the complex mechanisms underlying these associations.

Effects of Lobeglitazone, a Novel Thiazolidinedione, on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus over 52 Weeks

Background The aim of this multicenter, randomized, double-blind study was to examine the effect of lobeglitazone, a novel thiazolidinedione, on the changes in bone mineral density (BMD) in patients with type 2 diabetes mellitus. Methods A 24-week, double-blinded phase was followed by a 28-week, open-label phase, in which the placebo group also started to receive lobeglitazone. A total of 170 patients aged 34 to 76 years were randomly assigned in a 2:1 ratio to receive lobeglitazone 0.5 mg or a matching placebo orally, once daily. BMD was assessed using dual-energy X-ray absorptiometry at week 24 and at the end of the study (week 52). Results During the double-blinded phase, the femur neck BMD showed decreasing patterns in both groups, without statistical significance (−0.85%±0.36% and −0.78%±0.46% in the lobeglitazone and placebo groups, respectively). The treatment difference between the groups was 0.07%, which was also not statistically significant. Further, minimal, nonsignificant decreases were observed in both groups in the total hip BMD compared to values at baseline, and these differences also did not significantly differ between the groups. During the open-label phase, the BMD was further decreased, but not significantly, by −0.32% at the femur neck and by −0.60% at the total hip in the lobeglitazone group, and these changes did not significantly differ compared with the original placebo group switched to lobeglitazone. Conclusion Our results indicate that treatment with lobeglitazone 0.5 mg over 52 weeks showed no detrimental effect on the BMD compared to the placebo.

Trends in socioeconomic inequalities in five major risk factors for cardiovascular disease in the Korean population: A cross-sectional study using data from the Korea National Health and Nutrition Examination Survey, 2001-2014

Objectives To examine trends in socioeconomic inequalities in major cardiovascular disease (CVD) risk factors among the Korean population. Design Cross-sectional study. Setting A nationally representative population survey database. Participants A total of 42u2009725 Koreans, aged 25–64 years, who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) II (2001) to VI (2013–2014). Main outcome measures Trends in socioeconomic inequalities in five major CVD risk factors (smoking, obesity, diabetes, hypertension and hypercholesterolaemia). Results Gender differences were noted in the time trends in socioeconomic inequalities in smoking, obesity, diabetes and hypertension. Among men, low socioeconomic status (SES) was associated with higher prevalence of smoking, but not with obesity, diabetes or hypertension. The magnitudes of socioeconomic inequalities in smoking, obesity and diabetes remained unchanged, and the magnitude of the inequality in hypertension decreased over time. However, among women, low SES was associated with higher prevalence of smoking, obesity, diabetes and hypertension. Time trends towards increasing socioeconomic inequalities, measured by income, in smoking, obesity and diabetes were found in women. Unlike the other CVD risk factors, hypercholesterolaemia was not associated with socioeconomic inequality. Conclusions SES had a stronger impact on major CVD risk factors among Korean women than men. Moreover, socioeconomic inequalities in smoking, obesity and diabetes worsened among Korean women over time. Public policies to prevent smoking, obesity and diabetes in women with lower SES are needed to address inequalities.

Delay of insulin initiation in patients with type 2 diabetes mellitus inadequately controlled with oral hypoglycemic agents (analysis of patient- and physician-related factors): A prospective observational DIPP-FACTOR study in Korea

To assess the time to initiation of insulin therapy, and concurrently investigate both patient‐ and physician‐related factors associated with delaying insulin therapy in Korean patients with type 2 diabetes uncontrolled by oral hypoglycemic agents (OHAs).

Impact of carotid atherosclerosis detection on physician and patient behavior in the management of type 2 diabetes mellitus: a prospective, observational, multicenter study

BackgroundThis study compared carotid ultrasound (CUS) and traditional risk calculations in determining cardiovascular disease (CVD) risk in patients with type 2 diabetes mellitus (DM) and investigated whether awareness of CVD affects patient and/or physician behavior.MethodsIn this prospective, observational, multicenter study, 797 participants with type 2 diabetes were assessed using CUS, the United Kingdom Prospective Diabetes Study Risk Engine (UKPDSRE) calculator, and the Framingham Risk Score (FRS) algorithm. Health-related behaviors and physician treatments were compared at baseline and at 6xa0months after assessment.ResultsAccording to CUS, 43.5xa0% of the participants were at high risk (compared to 10.6xa0% and 4.3xa0% using the UKPDSRE and FRS approaches, respectively). Interestingly, 31.5xa0% of the patients with low risk scores according to the UKPDSRE calculator and 35.8xa0% of the patients with low risk scores according to the FRS algorithm were found to be at high risk according to CUS. The proportion of patients who achieved target LDL-C levels significantly increased after CUS. Moreover, increased awareness of atherosclerosis through CUS findings significantly altered physician treatment patterns and patient health-related behaviors.ConclusionsCarotid atherosclerosis was detected in more than 30xa0% of all participants with low or intermediate risk stratification scores. Improved awareness of atherosclerosis through CUS findings had a positive impact on both patient and physician behavior, resulting in improved CV risk management.

The effects of the Korean reference value on the prevalence of osteoporosis and the prediction of fracture risk

BackgroundSince the reference value is the core factor of the T-score calculation, it has a significant impact on the prevalence of osteoporosis. The purpose of this study was to determine the effects of using the Korean reference value on the prevalence of osteoporosis and on the prediction of fracture risk.MethodsWe used femoral neck bone mineral density (BMD) data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2008–2011. The Korean reference was identified by the mean and standard deviation of men and women aged 20–29 years. We compared the prevalence and the fracture risk assessment tool (FRAX™) probability obtained from the Korean reference and the NHANES III reference.ResultsIn men, the prevalence of osteoporosis increased when using the Korean men’s reference, and the difference increased up to 9% for those in their 80s. In women, the prevalence increased when using the NHANES III reference, and the difference increased up to 17% for those in their 80s. The reference value also affected the fracture risk probability, and the difference from changing the reference value increased in women and in subjects with more clinical fracture risk factors. In major osteoporotic fractures, the difference of the risk probability was up to 6% in women aged 70–79 years with two clinical risk factors. For femoral neck fractures, the difference was up to 7% in women aged 50–59 years with two clinical risk factors.ConclusionsWe confirmed that the reference value had significant effects on the prevalence of osteoporosis and on the fracture risk probability. The KNHANES 2008–2011 BMD data reflected the characteristics of the Korean BMD status well with regard to data size and study design; therefore, these data can be used as reference values.