Efficacy and safety of enavogliflozin vs. dapagliflozin as add-on therapy in patients with type 2 diabetes mellitus based on renal function: a pooled analysis of two randomized controlled trials.

BACKGROUND: We assessed the efficacy and safety of enavogliflozin (0.3 mg), a newly developed SGLT-2 inhibitor, in patients with type 2 diabetes mellitus based on kidney function via pooled analysis of two 24-week, randomized, double-blind phase III trials. METHODS: Data from 470 patients were included (enavogliflozin: 0.3 mg/day, n = 235; dapagliflozin: 10 mg/day, n = 235). The subjects were classified by mildly reduced (60 ≤ eGFR < 90 mL/min/1.73 m², n = 247) or normal eGFR (≥ 90 mL/min/1.73 m², n = 223). RESULTS: In the mildly reduced eGFR group, enavogliflozin significantly reduced the adjusted mean change of HbA1c and fasting plasma glucose levels at week 24 compared to dapagliflozin (- 0.94% vs. -0.77%, P = 0.0196). Enavogliflozin exhibited a more pronounced glucose-lowering effect by HbA1c when combined with dipeptidyl peptidase-4 inhibitors than that observed in their absence. Enavogliflozin showed potent blood glucose-lowering effects regardless of renal function. Conversely, dapagliflozin showed a significant decrease in the glucose-lowering efficacy as the renal function decreased. Enavogliflozin showed a higher urinary glucose excretion rate in both groups. The homeostatic model assessment showed that enavogliflozin markedly decreased the insulin resistance. The blood pressure, weight loss, or homeostasis model assessment of beta-cell function values did not differ significantly between enavogliflozin and dapagliflozin. Adverse events were similar between both drugs. CONCLUSIONS: The glucose-lowering efficacy of enavogliflozin is superior to that of dapagliflozin in patients with type 2 diabetes mellitus with mild renal function impairment; this is attributed to its potent urinary glucose excretion-promoting ability. The emergence of new and potent SGLT-2 inhibitors is considered an attractive option for patients with inadequate glycemic control and decreased renal function. TRIAL REGISTRATION: Not applicable (pooled analysis).

Fenofibrate's impact on cardiovascular risk in patients with diabetes: a nationwide propensity-score matched cohort study.

BACKGROUND: The beneficial effects of fenofibrate on atherosclerotic cardiovascular disease (ASCVD) outcomes in patients with diabetes and statin treatment are unclear. We investigated the effects of fenofibrate on all-cause mortality and ASCVD in patients with diabetes, high triglyceride (TG) levels and statin treatment. METHODS: We performed a nationwide propensity-score matched (1:1) cohort study using data from the National Health Information Database in the Republic of Korea from 2010 to 2017. The study included 110,723 individuals with diabetes, TG levels ≥ 150 mg/dL, and no prior diagnoses of ASCVD who used statins and fenofibrate, and an equal matched number of similar patients who used statins alone (control group). The study outcomes included newly diagnosed myocardial infarction (MI), stroke, both (MI and/or stroke), and all-cause mortality. RESULTS: Over a mean 4.03-year follow-up period, the hazard ratios (HR) for outcomes in the fenofibrate group in comparison to the control group were 0.878 [95% confidence interval (CI) 0.827-0.933] for MI, 0.901 (95% CI 0.848-0.957) for stroke, 0.897 (95% CI 0.858-0.937) for MI and/or stroke, and 0.716 (95% CI 0.685-0.749) for all-cause death. These beneficial effects of fenofibrate were consistent in the subgroup with TG 150-199 mg/dL but differed according to low-density lipoprotein cholesterol (LDL-C) levels. CONCLUSION: In this nationwide propensity-score matched cohort study involving individuals with diabetes and TG ≥ 150 mg/dL, the risk of all-cause death and ASCVD was significantly lower with fenofibrate use in conjunction with statin treatment compared to statin treatment alone. However, this finding was significant only in individuals with relatively high LDL-C levels.

Fenofibrate and risk of end-stage renal disease: A nationwide cohort study.

AIM: Previous studies have shown that fenofibrate improves outcomes such as albuminuria and estimated glomerular filtration rate decline. We hypothesize that fenofibrate has renoprotective effects and prevents or delays the development of end-stage renal disease. The objective of this study is to investigate the risk of incident end-stage renal disease in relation to fenofibrate treatment in patients who are already taking statins. MATERIALS AND METHODS: We performed a nationwide population-based cohort study using data from the Korea National Health Information Database from 2010 to 2017. Among adults using statins, 413 715 fenofibrate users were compared with 413 715 fenofibrate non-users after 1:1 age, sex and triglyceride matching. The endpoint of this study was incident end-stage renal disease. RESULTS: During a median 3.96-year follow-up, the incidence per 1000 person years of end-stage renal disease was lower in fenofibrate users than in fenofibrate non-users (0.885 vs. 0.960, p < 0.0001). The hazard ratio for end-stage renal disease was lower (0.763, 95% confidence interval 0.710-0.821) in fenofibrate users. This association was significant in patients with hypertension, proteinuria and an estimated glomerular filtration rate <60 mL/min/1.732. CONCLUSIONS: Fenofibrate use in patients taking statins with either hypertension, proteinuria, or decreased estimated glomerular filtration rate is associated with a low risk of incident end-stage renal disease. To confirm the renoprotective effect of fenofibrate in chronic kidney disease, a randomized controlled trial is warranted.

A cohort study found a high risk of end-stage kidney disease associated with acromegaly.

Acromegaly is a chronic systemic disease caused by excess levels of growth hormone and insulin-like growth factor-1 and is associated with numerous complications. Significantly, there is a lack of longitudinal data on kidney complications in patients with acromegaly. As such, we investigated the risk of end-stage kidney disease (ESKD) (stage 5D, 5T) in these patients with nationwide data obtained from the National Health Information Database of the National Health Insurance Service in Republic of Korea. A retrospective cohort study was conducted of 2.187 patients with acromegaly and 10,935 age- and sex-matched (1:5) control subjects without acromegaly over a mean follow-up period of 6.51 years. The study outcomes were analyzed using Cox proportional hazards regression analysis controlling for age, sex, household income, residential area, type 2 diabetes, hypertension, dyslipidemia, urolithiasis, congestive heart failure, myocardial infarction, stroke, and atrial fibrillation. The incidence (per 1,000 person-years) ESKD was 2.00 among patients with acromegaly but only 0.46 among controls, (hazard ratio 4.35 (95% confidence interval 2.63-7.20)) implicating a significantly higher risk. After adjustment for covariates, the risk of ESKD (2.36 (1.36-4.12)) was still significantly higher in patients with acromegaly than that in controls. Among the covariates, diabetes and hypertension were significant facilitators between acromegaly and ESKD in mediation analysis. Pituitary surgery and somatostatin analogues did not significantly change these associations. Thus, acromegaly may be linked with a higher risk for ESKD both independently and through mediators such as diabetes and hypertension.

Dietary intakes of branched-chain amino acids and plasma lipid profiles among filipino women in Korea: the Filipino Women's Diet and Health Study (FiLWHEL).

BACKGROUND: The potential role of dietary branched-chain amino acids (BCAA) in metabolic health, including cardiovascular disease and diabetes, is evolving, and it is yet to be understood if dietary BCAA intakes are associated with plasma lipid profiles or dyslipidaemia. This study tested the association of dietary BCAA intakes with plasma lipid profiles and dyslipidaemia among Filipino women in Korea. METHODS: Energy-adjusted dietary BCAA intakes (isoleucine, leucine, valine, and total BCAA) and fasting blood profiles of triglycerides (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) were determined in a sample of 423 women enrolled in the Filipino Women's Diet and Health Study (FiLWHEL). The generalized linear model was applied to estimate least-square (LS) means and 95% confidence intervals (CIs) and compare plasma TG, TC, HDL-C, and LDL-C across tertile distribution of energy-adjusted dietary BCAA intakes at P < 0.05. RESULTS: Mean of energy-adjusted dietary total BCAA intake was 8.3 ± 3.9 g/d. Average plasma lipid profiles were 88.5 ± 47.4 mg/dl for TG, 179.7 ± 34.5 mg/dl for TC, 58.0 ± 13.7 mg/dl for HDL-C, and 104.0 ± 30.5 mg/dl for LDL-C. LS means, and 95% CIs across tertiles of energy-adjusted total BCAA intakes were 89.9 mg/dl, 88.8 mg/dl and 85.8 mg/dl (P-trend = 0.45) for TG, 179.1 mg/dl, 183.6 mg/dl and 176.5 mg/dl (P-trend = 0.48) for TC, 57.5 mg/dl, 59.6 mg/dl and 57.1 mg/dl (P-trend = 0.75) for HDL-C and 103.6 mg/dl, 106.2 mg/dl and 102.3 mg/dl (P-trend = 0.68) for LDL-C. Furthermore, the multivariable-adjusted prevalence ratios and 95% confidence intervals for dyslipidaemia across increasing tertile distribution of energy-adjusted total BCAA intake were; 1.00, 0.67 (0.40, 1.13) and 0.45 (0.16, 1.27; P-trend = 0.03) for the first, second and third tertile, respectively. CONCLUSIONS: Higher dietary intakes of BCAA presented a statistically significant inverse trend with the prevalence of dyslipidaemia among Filipino women in this study and testing these associations in longitudinal studies may be necessary to confirm these findings.

Comparison of cardiovascular disease risk factors among FiLWHEL (2014-2016), NNS (2013) and KNHANES (2013-2015) women.

OBJECTIVES: This study assessed the CVD risk factors among Filipino women (FW) in Korea and compared them with FW in the Philippines and women in Korea (KW). METHODS: A cohort of 504 women from the Filipino Women's Health and Diet Study (FiLWHEL) aged 20-57 years old were age-matched (1:1 ratio) with women from the 2013 National Nutrition Survey in the Philippines and the 2013-2015 Korean National Health and Nutrition Examination Survey. Anthropometric data, blood pressure (BP), lipid and glucose levels were compared across the four populations by calculating the odds ratio (OR)s and 95% confidence interval (CI)s using conditional logistic regression models. RESULTS: Compared to KW, FW in Korea and FW in the Philippines were more than 2 and 3 times higher odds of having obesity for BMI ≥ 30 kg/m2 and waist circumference ≥ 88 cm, respectively. However, FW in Korea had the highest odds (OR 5.51, 95% CI 3.18-9.56) of having hypertension compared to KW. FW in the Philippines had the highest odds of having dyslipidemia (compared to KW, total cholesterol ≥ 200 mg/dL: OR 8.83, 95% CI 5.30-14.71; LDL-C ≥ 130 mg/dL: OR 3.25, 95% CI 2.13-4.98; and triglyceride ≥ 150 mg/dL: OR 2.59, 95% CI 1.59-4.22), but FW in Korea and KW had similar prevalence of dyslipidemia. CONCLUSIONS: FW in Korea had higher prevalence of obesity and hypertension, with similar prevalence of dyslipidemia compared to KW in this sample. FW in the Philippines had higher prevalence of dyslipidemia compared to FW in Korea. Further prospective studies are warranted to examine the CVD risk factors among continental and native-born Filipino women.

Acromegaly and cardiovascular outcomes: a cohort study.

AIMS: Cardiovascular disease is a common complication in acromegaly. We investigated the risk of cardiovascular disease and mortality in patients with acromegaly in a large-scale population using nationwide data in Korea. METHODS AND RESULTS: We performed a nationwide, retrospective, observational, cohort study of patients with acromegaly (n = 1874) and age- and sex-matched subjects without acromegaly (n = 9370) for a mean follow-up of 7.5 ± 3.2 years. The study outcomes were myocardial infarction, stroke, atrial fibrillation, congestive heart failure, and all-cause death. All outcomes were analysed by Cox proportional hazards regression analysis while controlling for age, sex, household income, place, Type 2 diabetes, hypertension, and dyslipidaemia. The incidence (per 1000 person-years) of atrial fibrillation (3.06 vs. 1.70; P = 0.001), congestive heart failure (3.11 vs. 1.63; P < 0.001), and all-cause mortality (6.31 vs. 4.03; P < 0.001) in patients with acromegaly was higher than in controls. However, the incidence of myocardial infarction and stroke did not differ between groups. After adjustment for covariates, the risk for atrial fibrillation [hazard ratio (HR): 1.59; 95% confidence interval (CI): 1.09-2.31], congestive heart failure (HR: 1.54; 95% CI: 1.06-2.25), and all-cause mortality (HR: 1.31; 95% CI: 1.01-1.69) was significantly higher in patients with acromegaly. In time lag sensitivity analysis, a higher risk for atrial fibrillation was observed only in the first 4 years after diagnosis in acromegaly patients compared with controls (HR: 3.05; 95% CI: 1.94-4.79). CONCLUSION: Patients with acromegaly were at higher risk for atrial fibrillation, congestive heart failure, and all-cause death. The risk of atrial fibrillation had a time-dependent association with acromegaly.

Evaluating Triglyceride and Glucose Index as a Simple and Easy-to-Calculate Marker for All-Cause and Cardiovascular Mortality.

OBJECTIVE: The triglyceride and glucose (TyG) index is a useful marker of insulin resistance and is a predictor of several metabolic diseases. The aim of this study was to evaluate the association between the TyG index and all-cause or cardiovascular mortality using a large population-based cohort study database. METHODS: A total of 255,508 subjects in the Kangbuk Samsung Health Study cohort were enrolled. Cox proportional hazards models were used to analyze the risk of mortality. RESULTS: During a median 5.7-year follow-up, the cumulative all-cause and cardiovascular mortality was 0.47% and 0.07%. There was a nonlinear relationship between the TyG index and death, and moving from moderate to high, the TyG index levels were associated with an increase in the risk of death. The hazard ratio (HR) for all-cause and cardiovascular mortality of the TyG index was 1.21 [95% confidence interval (CI) 1.14-1.28] and 1.45 (95% CI 1.26-1.66) in the unadjusted model, respectively. After adjustment for covariates, the association between the TyG index and all-cause and cardiovascular mortality was attenuated. In the multivariable-adjusted model, the TyG index was associated with an elevated risk of all-cause mortality in women (HR 1.13, 95% CI 1.02-1.26) and a decreased risk in men (HR 0.92, 95% CI 0.85-0.99). The association between cardiovascular mortality and the TyG index was not statistically significant among either men or women in the multivariable-adjusted model. CONCLUSIONS: The TyG index in a young, relatively healthy, population is associated with an elevated risk of all-cause and cardiovascular mortality. This association between the TyG index and all-cause mortality persists in women after multivariable adjustment.

Dietary branched-chain amino acids and odds of obesity among immigrant Filipino women: the Filipino women's diet and health study (FiLWHEL).

BACKGROUND: The dietary environment promoting adiposity keeps evolving and of interest is the significance of dietary branched-chain amino acids (BCAA). This study assessed the association between dietary BCAA intakes and odds of obesity among immigrant Filipino women in Korea. METHOD: We included 423 immigrant Filipino women enrolled in the Filipino Women's diet and health study in the Republic of Korea. Dietary BCAA intakes were estimated from 24 hour recalls and adjusted for energy intake using the residual method. General obesity was derived from direct anthropometric measurements (height, weight and waist circumference - WC) and defined as body mass index (BMI) ≥25 kg/m2 and abdominal obesity as WC ≥80 cm. Odds ratios (OR) and 95% confidence intervals (CI) by tertile distribution of energy-adjusted BCAA intakes were estimated using multivariable logistic regression with a two-sided P < 0.05. RESULTS: Median (interquartile range) for BCAA intakes in g/day were; 7.9 (5.8, 10.3) g/day for total BCAA; 2.0 (1.5, 2.6) g/day for isoleucine, 3.5(2.5, 4.6) g/day for leucine and 2.4 (1.8, 3.1) g/day for valine. Mean BMI and WC were 23.6 ± 3.8 kg/m2 and 79.8 ± 9.3 cm, respectively. Also, 30.2% (128) had BMI ≥25 kg/m2 and 42.0% (178) had WC ≥80 cm. ORs (95%CIs) of general obesity across tertile distribution of energy-adjusted total BCAA intakes were 1.00, 0.81 (0.47, 1.37) and 0.62 (0.36, 1.07; P for trend = 0.08). A similar trend was observed across tertile distribution of energy-adjusted isoleucine, leucine and valine intakes. However, there was a statistically significant inverse association between total BCAA intake and odds of general obesity in a subset of non-smokers; 1.00, 0.68 (0.39, 1.20) and 0.55 (0.31, 0.98; P for trend = 0.04). CONCLUSION: We found a suggestive inverse association between higher dietary BCAA intake and odds of obesity in this sample of immigrant Filipino women, particularly among non-smokers. Prospective cohort studies among the immigrant population will be necessary to verity these findings.

Cardiovascular safety of evogliptin in patients with type 2 diabetes: A nationwide cohort study.

AIM: To assess whether the use of evogliptin, a novel dipeptidyl peptidase-4 inhibitor (DPP-4i), was associated with an increased risk of cardiovascular events compared with glimepiride in patients with type 2 diabetes (T2D). METHODS: We conducted a population-based cohort study using South Korea's nationwide healthcare database from 1 January 2014 to 31 December 2018. We identified a base cohort of patients with T2D who newly initiated metformin monotherapy, from which we identified a study cohort of patients who either added or switched to glimepiride or DPP-4is (including evogliptin). Patients were followed up from initiation of DPP-4is or glimepiride until the earliest of either outcome occurrence or 31 December 2018. Our primary outcome was hospitalization or an emergency visit for cardiovascular events, a composite endpoint comprised of cerebrovascular events, heart failure, myocardial infarction, transient ischaemic attack, angina pectoris and revascularization procedures; secondary outcomes were the individual components of the primary outcome. A multivariable Cox proportional hazards model was used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the risk of study outcomes associated with evogliptin compared with glimepiride. RESULTS: Our base and study cohorts had 317,307 and 128,788 patients, respectively, of which 100,038 were DPP-4i users (2946 were evogliptin users) and 28,750 were glimepiride users within the study cohort. The median follow-up was 195 days for evogliptin and 113 days for glimepiride users. Compared with glimepiride, evogliptin was associated with a reduced risk of the primary outcome (aHR 0.67, 95% CI 0.48-0.95) and cerebrovascular events (aHR 0.41, 95% CI 0.22-0.78) but showed non-significant associations for myocardial infarction (aHR 0.63, 95% CI 0.27-1.46), heart failure (aHR 0.35, 95% CI 0.09-1.47), transient ischaemic attack (aHR 0.23, 95% CI 0.03-1.72) and angina pectoris (aHR 1.35, 95% CI 0.82-2.21). CONCLUSIONS: Findings from this population-based cohort study provide novel real-world evidence that the use of evogliptin, compared with glimepiride, did not increase the risk of cardiovascular events, including cerebrovascular events, myocardial infarction, heart failure, transient ischaemic attack and angina pectoris.

The triglyceride glucose index is a simple and low-cost marker associated with atherosclerotic cardiovascular disease: a population-based study.

BACKGROUND: The triglyceride glucose (TyG) index is an inexpensive clinical surrogate marker for insulin resistance. However, the relationship between TyG index and atherosclerotic cardiovascular disease (CVD) remains unclear. We evaluated the relationship between TyG index and CVD using a large-scale population dataset from the National Health Information Database (NHID). METHODS: We performed a retrospective observational cohort study of 5,593,134 persons older than 40 years from 2009 to 2017 using the NHID. We divided the participants into TyG index quartiles. Outcome variables were stroke, myocardial infarction, and both. The incidence of outcomes was estimated for each TyG quartile over the total follow-up period. All outcomes were analyzed by Cox proportional hazards regression analysis while controlling for baseline covariates. RESULTS: During 8.2 years of mean follow-up, stroke was diagnosed in 89,120 (1.59%), MI in 62,577 (1.12%), and both stroke and MI in 146,744 (2.62%) participants. Multivariate-adjusted hazard ratios (HRs) for patients in the highest TyG index quartile demonstrated that these patients were at higher risk for stroke (HR = 1.259; 95% confidence interval [CI] 1.233-1.286), for MI (HR = 1.313; 95% CI 1.28-1.346), and for both (HR = 1.282; 95% CI 1.261-1.303) compared with participants in the lowest TyG index quartile. These effects were independent of age, sex, smoking, alcohol consumption, physical activity, body mass index, systolic blood pressure, and total cholesterol. CONCLUSIONS: In our large population study, TyG index, a simple measure reflecting insulin resistance, was potentially useful in the early identification of individuals at high risk of experiencing a cardiovascular event.

Randomized control trial comparing the effect of cilostazol and aspirin on changes in carotid intima-medial thickness.

Antiplatelet drugs are effective in preventing recurrence of atherosclerosis in type 2 diabetes (T2D) patients. However, the efficacy and usefulness of antiplatelet drugs on the progression of carotid intima-media thickness (IMT), a marker for evaluating early atherosclerotic vascular disease, has not been analyzed. We conducted a prospective, randomized, open, 36-month trial comparing cilostazol vs. aspirin. A total of 415 T2D patients (age range 38-83 years; 206 females) without macrovascular complications were randomized to either an aspirin (100 mg/day) or cilostazol (200 mg/day) treatment. Patients underwent B-mode ultrasonography annually to assess the IMT and serum levels of inflammatory markers were measured before and after each treatment. Potential confounders were statistically adjusted, and included lipid profiles, HbA1c, body mass index, waist circumference, anti-hypertensive and statin medications. The decrease in mean left, maximum left, mean right and maximum right IMT were significantly greater with cilostazol compared with aspirin (- 0.094 ± 0.186 mm vs. 0.006 ± 0.220 mm, p < 0.001; - 0.080 ± 0.214 mm vs. 0.040 ± 0.264 mm, p < 0.001; - 0.064 ± 0.183 mm vs. 0.004 ± 0.203 mm, p = 0.015; - 0.058 ± 0.225 mm vs. 0.023 ± 0.248 mm, p = 0.022, respectively). And these differences remained significant after adjustment of potential confounders. Compared with aspirin, cilostazol treatment was associated with significantly increased HDL cholesterol (p = 0.039) and 25-hydroxy vitamin D levels (p = 0.001). Cilostazol treatment was associated with significantly lowered IMT in T2D patients compared to aspirin, independent of conventional cardiovascular risk factors. Cilostazol may inhibit plaque formation and have beneficial effects on atherosclerosis through vasodilatory and antiplatelet effects.

Dietary diversity and nutritional adequacy among married Filipino immigrant women: The Filipino Women's Diet and Health Study (FiLWHEL).

BACKGROUND: Migration has an influence on health behavior and food intake. Dietary variety is a key component to high-quality diets because a single food item does not contain a variety of nutrients and may not reflect nutritional adequacy. We aimed to compare the dietary diversity scores (DDS), food variety scores (FVS), and nutrient adequacy levels of married Filipino immigrant women in Korea to those of Korean women. METHODS: We matched the data of 474 participants aged 20-57 years from the Filipino Women's Diet and Health Study (FiLWHEL) by age category with those of married Korean women randomly selected from the Korea National Health and Nutrition Examination Survey (KNHANES). Dietary information in FiLWHEL and KNHANES were assessed through the 24-hour recall method. We calculated the DDS by summing the number of eleven food groups consumed (DDS 10 g if they consumed at least 10 g/day; DDS all if they consumed any amount) and the FVS by counting the number of food items consumed. For nutrient adequacy, we calculated the probability of adequacy (PA) and intake below the estimated average requirement (EAR). RESULTS: Filipino women had a lower DDS and FVS in comparison to Korean women. The means (±SDs) of DDS 10 g, DDS all, and FVS for Filipino women versus Korean women were 6.0 (±1.6) versus 6.8 (±1.5) (p < 0.001), 6.7 (±1.7) versus 7.9 (±1.4) (p < 0.001) and 9.2 (±3.3) versus 14.7 (±4.9) (p < 0.001), respectively. When we compared each food group, the intakes of fish, other seafood, legumes/seeds/nuts, eggs, vegetables, and fruits were lower for Filipino women than for Korean women. The mean probability of adequacy (MPA) of nutrient intake of the nine selected nutrients was lower for Filipino women in comparison to Korean women. The mean (±SD) was 0.55 (±0.28) versus 0.66 (±0.26), respectively. CONCLUSIONS: Our findings showed that married Filipino immigrant women in Korea had lower dietary variety scores in comparison to Korean women. This was reflected in their nutritional adequacy. Nutrition education focusing on the promotion of eating a variety of foods may be needed for Filipino immigrant women in Korea.

Efficacy and safety of adding evogliptin versus sitagliptin for metformin-treated patients with type 2 diabetes: A 24-week randomized, controlled trial with open label extension.

AIMS: This trial consisted of a 24-week multicentre, randomized, double-blind, double-dummy, active-controlled study and a 52-week open label extension study to assess the efficacy and safety of evogliptin, a novel dipeptidyl peptidase-4 inhibitor, compared to sitagliptin in patients with type 2 diabetes who have inadequate glycaemic control with metformin alone. METHODS: Adult patients with type 2 diabetes mellitus (N = 222) with HbA1c 6.5% to 11% who were receiving stable doses of metformin (≥1000 mg/d) were randomized 1:1 to add-on evogliptin 5 mg (N = 112) or sitagliptin 100 mg (N = 110) once daily for 24 weeks. The primary efficacy analysis consisted of a comparison of the change from baseline HbA1c at week 24. Non-inferiority was concluded if the upper limit of the 2-sided 95% confidence interval for the HbA1c difference between treatments was <0.35%. RESULTS: Mean changes in HbA1c following addition of evogliptin or sitagliptin were -0.59% and -0.65%, respectively. The between-group difference was 0.06% (2-sided 95% confidence interval, -0.10 to 0.22), demonstrating non-inferiority. After the 52-week treatment, evogliptin caused a persistently decreased level of HbA1c (-0.44% ± 0.65%, P < .0001). In general, both treatments were well tolerated, with incidences and types of adverse events comparable between the two groups. Hypoglycaemic events, mostly mild, were reported in 0.9% of patients treated with evogliptin and in 2.8% of patients treated with sitagliptin for 24 weeks. CONCLUSIONS: Evogliptin 5 mg added to metformin therapy effectively improved glycaemic control and was non-inferior to sitagliptin and well tolerated in patients with type 2 diabetes mellitus that was inadequately controlled by metformin alone.

Scaling of adult regional body mass and body composition as a whole to height: Relevance to body shape and body mass index.

OBJECTIVES: Adult body mass (MB) empirically scales as height (Ht) squared (MB ∝ Ht(2) ), but does regional body mass and body composition as a whole also scale as Ht(2) ? This question is relevant to a wide range of biological topics, including interpretation of body mass index (BMI). METHODS: Dual-energy X-ray absorptiometry (DXA) was used to quantify regional body mass [head (MH), trunk, arms, and legs] and whole-body composition [fat, lean soft tissue (LST), and bone mineral content (BMC)] in non-Hispanic (NH) white, NH black, Mexican American, and Korean adults participating in the National Health and Nutrition Examination Survey (NHANES; n = 17,126) and Korean NHANES (n = 8,942). Regression models were developed to establish Ht scaling powers for each measured component with adjustments for age and adiposity. RESULTS: Exploratory analyses revealed a consistent scaling pattern across men and women of the four population groups: regional mass powers, head (∼0.8-1) < arms and trunk (∼1.8-2.3) < legs (∼2.3-2.6); and body composition, LST (∼2.0-2.3) < BMC (∼2.1-2.4). Small sex and population differences in scaling powers were also observed. As body mass scaled uniformly across the eight sex and population groups as Ht(∼2) , tall and short subjects differed in body shape (e.g., MH/MB ∝ Ht(-∼1) ) and composition. CONCLUSIONS: Adult human body shape and relative composition are a function of body size as represented by stature, a finding that reveals a previously unrecognized phenotypic heterogeneity as defined by BMI. These observations provide new pathways for exploring mechanisms governing the interrelations between adult stature, body morphology, biomechanics, and metabolism.

Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study.

OBJECTIVE: To investigate the risk of non-alcoholic fatty liver disease (NAFLD) for cardiovascular disease and all cause death in patients with type 2 diabetes mellitus (T2DM). DESIGN: Nationwide population based study. SETTING: Longitudinal cohort study in Korea. PARTICIPANTS: 7 796 763 participants in the National Health Screening Programme in 2009 were divided into three groups based on NAFLD status: no NAFLD (fatty liver index<30); grade 1 NAFLD (30≤fatty liver index<60); and grade 2 NAFLD (fatty liver index≥60). Median follow-up was 8.13 years. MAIN OUTCOME MEASURES: The primary outcome was incident cardiovascular disease (myocardial infarction, ischaemic stroke) or all cause death. RESULTS: Of 7 796 763 participants, 6.49% (n=505 763) had T2DM. More patients with T2DM had grade 1 NAFLD (34.06%) and grade 2 NAFLD (26.73%) than those without T2DM (grade 1 NAFLD: 21.20%; grade 2 NAFLD: 10.02%). The incidence rate (per 1000 person years) of cardiovascular disease and all cause death increased in the order of no NAFLD, grade 1 NAFLD, and grade 2 NAFLD, and the incidence rates in patients with T2DM were higher than those in patients without T2DM. The five year absolute risk for cardiovascular disease and all cause death increased in the order of no NAFLD, grade 1 NAFLD, and grade 2 NAFLD in patients without and with T2DM (no NAFLD, without T2DM: 1.03, 95% confidence interval 1.02 to 1.04, and 1.25, 1.24 to 1.26, respectively; grade 1 NAFLD, without T2DM: 1.23, 1.22 to 1.25, and 1.50, 1.48 to 1.51, respectively; grade 2 NAFLD, without T2DM: 1.42, 1.40 to 1.45, and 2.09, 2.06 to 2.12, respectively; no NAFLD, with T2DM: 3.34, 3.27 to 3.41, and 3.68, 3.61 to 3.74, respectively; grade 1 NAFLD, with T2DM: 3.94, 3.87 to 4.02, and 4.25, 4.18 to 4.33, respectively; grade 2 NAFLD, with T2DM: 4.66, 4.54 to 4.78, and 5.91, 5.78 to 6.05, respectively). Patients with T2DM and without NAFLD had a higher five year absolute risk for cardiovascular disease and all cause death than those without T2DM and with grade 2 NAFLD. Risk differences for cardiovascular disease and all cause death between no NAFLD and grade 1 or grade 2 NAFLD were higher in patients with T2DM than in those without T2DM. CONCLUSIONS: NAFLD in patients with T2DM seems to be associated with a higher risk of cardiovascular disease and all cause death, even in patients with mild NAFLD. Risk differences for cardiovascular disease and all cause death between the no NAFLD group and the grade 1 or grade 2 NAFLD groups were higher in patients with T2DM than in those without T2DM.

Clinical Characteristics of Patients With Statin Discontinuation in Korea: A Nationwide Population-Based Study.

Objective: To investigate the clinical characteristics of patients with statin discontinuation in Korea, using a nationwide database. Methods: We analyzed 1,308,390 patients treated with statin for the first time in their life between 2016 and 2017 using the Korean National Health Information Database. The patients participated in the Korean National Health Screening Program within two years before taking statin. Patients with statin discontinuation were defined as those who were not prescribed statin between 365 days and 730 days after the initial statin prescription. Results: The overall prevalence of statin discontinuation was 39.44%. Patients with statin discontinuation were younger, had lower body mass index (BMI), included a higher number of smokers and drinkers, did not exercise regularly, with fewer cases of hypertension and diabetes mellitus than those without statin discontinuation (p<0.001). Compared with patients aged 20-29 years, the risk of statin discontinuation showed a U-shaped relationship with age (odds ratios [ORs]: 0.619 in 30-39 years; 0.454 in 40-49 years; 0.345 in 50-59 years; 0.307 in 60-69 years; 0.324 in 70-79 years; and 0.415 in ≥80 years). In addition, increased BMI was associated with decreased risk of statin discontinuation (ORs: 0.969 with 25.0-29.9 kg/m2, and 0.890 with ≥30.0 kg/m2). Patients with hypertension and diabetes mellitus were at a lower risk of statin discontinuation (OR: 0.414 for hypertension; 0.416 for diabetes mellitus). Conclusion: The prevalence of patients with statin discontinuation in Korea was 39.44% at 1 to 2 years after initial statin treatment.

Cardiovascular safety of evogliptin dual and triple therapy in patients with type 2 diabetes: a nationwide cohort study.

OBJECTIVE: To investigate the risk of cardiovascular events associated with commonly used dual and triple therapies of evogliptin, a recently introduced dipeptidyl peptidase-4 inhibitor (DPP4i), for managing type 2 diabetes in routine clinical practice. DESIGN: A retrospective cohort study. SETTING: Korean Health Insurance Review and Assessment database. PARTICIPANTS: Patients who initiated metformin-based dual therapy and metformin+sulfonylurea-based triple therapy in South Korea from 2014 to 2018. INTERVENTIONS: Initiation of combination therapy with evogliptin. PRIMARY AND SECONDARY OUTCOME MEASURES: Hazards of cardiovascular events, a composite endpoint of myocardial infarction, heart failure and cerebrovascular events, and its individual components. Cox proportional hazards model with propensity score-based inverse probability of treatment weighting were used to estimate HRs and 95% CIs. RESULTS: From the dual and triple therapy cohorts, 5830 metformin+evogliptin users and 2198 metformin+sulfonylurea+evogliptin users were identified, respectively. Metformin+evogliptin users, as compared with metformin+non-DPP4i, had a 29% reduced risk of cardiovascular events (HR 0.71, 95% CI 0.62 to 0.82); HRs for individual outcomes were cerebrovascular events (0.71, 95% CI 0.53 to 0.95), heart failure (0.70, 95% CI 0.59 to 0.82), myocardial infarction (0.89, 95% CI 0.60 to 1.31). Metformin+sulfonylurea+evogliptin users, compared with metformin+sulfonylurea+non-DPP4i, had a 24% reduced risk of cardiovascular events (0.76, 95% CI 0.59 to 0.97); HRs for individual outcomes were myocardial infarction (0.57, 95% CI 0.27 to 1.19), heart failure (0.74, 95% CI 0.55 to 1.01), cerebrovascular events (0.96, 95% CI 0.61 to 1.51). CONCLUSIONS: These findings suggest that dual or triple therapies of evogliptin for the management of type 2 diabetes in routine clinical practice present no cardiovascular harms, but could alternatively offer cardiovascular benefits in this patient population.

Differences in segmental fat accumulation patterns by sex and ethnicity: An international approach.

Excess fat on the body impacts obesity-related co-morbidity risk; however, the location of fat stores affects the severity of these risks. The purpose of this study was to examine segmental fat accumulation patterns by sex and ethnicity using international datasets. An amalgamated and cross-calibrated dataset of dual x-ray absorptiometry (DXA)-measured variables compiled segmental mass for bone mineral content (BMC), lean mass (LM), and fat mass (FM) for each participant; percentage of segment fat (PSF) was calculated as PSFsegment = (FMsegment/(BMCsegment + LMsegment + FMsegment)) × 100. A total of 30 587 adults (N = 16 490 females) from 13 datasets were included. A regression model was used to examine differences in regional fat mass and PSF. All populations followed the same segmental fat mass accumulation in the ascending order with statistical significance (arms < legs < trunk), except for Hispanic/Latinx males (arms < [legs = trunk]). Relative fat accumulation patterns differed between those with greater PSF in the appendages (Arab, Mexican, Asian, Black, American Caucasian, European Caucasian, and Australasian Caucasian females; Black males) and those with greater PSF in the trunk (Mexican, Asian, American Caucasian, European Caucasian, and Australasian Caucasian males). Greater absolute and relative fat accumulation in the trunk could place males of most ethnicities in this study at a higher risk of visceral fat deposition and associated co-morbidities.

Risk of depression in patients with acromegaly in Korea (2006-2016): a nationwide population-based study.

BACKGROUND: An increased prevalence of depression has been reported in patients with acromegaly. However, most studies included a relatively small sample size owing to the rarity of acromegaly. We aimed to investigate the risk of depression in patients with acromegaly using the Korean National Health Information Database (NHID). METHODS: The data of patients with acromegaly in 2006-2016 were collected from the rare incurable disease registry of the NHID. Patients with acromegaly were matched with control participants without acromegaly for age and sex in a 1:5 ratio. RESULTS: Patients who did not receive treatment for acromegaly had a significantly increased risk of depression (hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.12-1.82). However, the risk of depression did not increase in patients who received treatment for acromegaly. The multiple Cox regression analysis showed that the risk of depression was significantly higher in the untreated group than in the control group during the first 3 years of observation (HR: 1.829, 95% CI: 1.305-2.563). However, after a time lag of over 3 years, the risk of depression decreased in the untreated group, which is similar to that in the control group. CONCLUSION: Our nationwide study suggests that patients who did not receive treatment for acromegaly have a higher risk of depression compared with controls. The untreated acromegaly patients should be monitored for the development of depression, especially in the early years after diagnosis. These results could serve as a basis for developing screening strategies to mitigate depression in acromegaly patients.