Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).
From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.
In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%;
This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.
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Circulating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in patients with type 2 diabetes mellitus.
Postmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE,
In the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (
Exercise training resulted in a significant decrease in the circulating ApoJ level, with changes in ApoJ associated with an improvement in some insulin resistance indices. These data suggest that circulating ApoJ may be a useful metabolic marker for assessing the effects of exercise on insulin resistance.
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This study was a multicenter, parallel-group, double-blind, double-dummy, randomized, noninferiority trial to evaluate the efficacy and safety of γ-linolenic acid (GLA) relative to α-lipoic acid (ALA) over a 12-week treatment period in type 2 diabetes mellitus (T2DM) patients with painful diabetic peripheral neuropathy (DPN).
This study included 100 T2DM patients between 20 and 75 years of age who had painful DPN and received either GLA (320 mg/day) and placebo or ALA (600 mg/day) and placebo for 12 weeks. The primary outcome measures were mean changes in pain intensities as measured by the visual analogue scale (VAS) and the total symptom scores (TSS).
Of the 100 subjects who initially participated in the study, 73 completed the 12-week treatment period. Per-protocol analyses revealed significant decreases in the mean VAS and TSS scores compared to baseline in both groups, but there were no significant differences between the groups. The treatment difference for the VAS (95% confidence interval [CI]) between the two groups was −0.65 (−1.526 to 0.213) and the upper bound of the 95% CI did not exceed the predefined noninferiority margin (δ1=0.51). For the TSS, the treatment difference was −0.05 (−1.211 to 1.101) but the upper bound of the 95% CI crossed the noninferiority margin (δ2=0.054). There were no serious adverse events associated with the treatments.
GLA treatment in patients with painful DPN was noninferior to ALA in terms of reducing pain intensity measured by the VAS over 12 weeks.
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There is limited information regarding the optimal third-line therapy for managing type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. This study assessed the efficacy and safety of pioglitazone or glimepiride when added to metformin plus alogliptin treatment for T2DM.
This multicenter, randomized, active-controlled trial (
Glycosylated hemoglobin levels exhibited similar significant decreases in both groups during the treatment period (pioglitazone: −0.81%,
Among patients with T2DM inadequately controlled using metformin plus alogliptin, the addition of pioglitazone provided comparable glycemic control and various benefits (improvements in lipid profiles, insulin resistance, and hypoglycemia risk) relative to the addition of glimepiride.
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Chronic exposure to elevated levels of free fatty acids contributes to pancreatic β-cell dysfunction. Although it is well known that metformin induces cellular energy depletion and a concomitant activation of AMP-activated protein kinase (AMPK) through inhibition of the respiratory chain, previous studies have shown inconsistent results with regard to the action of metformin on pancreatic β-cells. We therefore examined the effects of metformin on pancreatic β-cells under lipotoxic stress.
NIT-1 cells and mouse islets were exposed to palmitate and treated with 0.05 and 0.5 mM metformin. Cell viability, glucose-stimulated insulin secretion, cellular adenosine triphosphate, reactive oxygen species (ROS) levels and Rho kinase (ROCK) activities were measured. The phosphorylation of AMPK was evaluated by Western blot analysis and mRNA levels of endoplasmic reticulum (ER) stress markers and NADPH oxidase (NOX) were measured by real-time quantitative polymerase chain reaction analysis.
We found that metformin has protective effects on palmitate-induced β-cell dysfunction. Metformin at a concentration of 0.05 mM inhibits NOX and suppresses the palmitate-induced elevation of ER stress markers and ROS levels in a AMPK-independent manner, whereas 0.5 mM metformin inhibits ROCK activity and activates AMPK.
This study suggests that the action of metformin on β-cell lipotoxicity was implemented by different molecular pathways depending on its concentration. Metformin at a usual therapeutic dose is supposed to alleviate lipotoxic β-cell dysfunction through inhibition of oxidative stress and ER stress.
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Thyroid disease and metabolic syndrome are both associated with cardiovascular disease. The aim of this study was to investigate the correlation between thyroid hormones and obesity sub-phenotypes using nationwide data from Korea, a country known to be iodine replete.
This study was based on data obtained from the sixth Korea National Health and Nutrition Examination Survey, administered from 2013 to 2015. A total of 13,873 participants aged ≥19 years were included, and classified into four groups: metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO) by body fat on the basis of body mass index and metabolic health.
At baseline, serum free thyroxine (fT4) values were significantly higher in the MHNO phenotype (MHNO, 1.27±0.01 ng/dL; MHO, 1.25±0.01 ng/dL; MUNO, 1.24±0.01 ng/dL; MUO, 1.24±0.01 ng/dL,
Although there was a difference by age and sex, we found that the decrease of TSH and the increase of fT4 values were associated with MHNO.
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Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naïve newly-diagnosed type 2 diabetes mellitus.
A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was measured at week 24.
The reduction in the levels of HbA1c was −1.62%±0.07% in the vogmet group and −1.31%±0.07% in the metformin group (
Vogmet is a safe antihyperglycemic agent that controls blood glucose level effectively, yields weight loss, and is superior to metformin in terms of various key glycemic parameters without increasing the risk of hypoglycemia.
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We evaluated the clinical characteristics of insulin resistance and β-cell dysfunction in newly diagnosed, drug-naive people with type 2 diabetes by analyzing nationwide cross-sectional data.
We collected the clinical data of 912 participants with newly diagnosed diabetes from 83 primary care clinics and hospitals nationwide from 2015 to 2016. The presence of insulin resistance and β-cell dysfunction was defined as a homeostatic model assessment of insulin resistance (HOMA-IR) value ≥2.5 and fasting C-peptide levels <1.70 ng/mL, respectively.
A total of 75.1% and 22.6% of participants had insulin resistance and β-cell dysfunction, respectively. The proportion of participants with insulin resistance but no β-cell dysfunction increased, and the proportion of participants with β-cell dysfunction but no insulin resistance decreased as body mass index (BMI) increased. People diagnosed with diabetes before 40 years of age had significantly higher HOMA-IR and BMI than those diagnosed over 65 years of age (HOMA-IR, 5.0 vs. 3.0; BMI, 28.7 kg/m2 vs. 25.1 kg/m2). However, the β-cell function indices were lower in people diagnosed before 40 years of age than in those diagnosed after 65 years of age (homeostatic model assessment of β-cell function, 39.3 vs. 64.9; insulinogenic index, 10.3 vs. 18.7; disposition index, 0.15 vs. 0.25).
We observed that the main pathogenic mechanism of type 2 diabetes is insulin resistance in participants with newly diagnosed type 2 diabetes. In addition, young adults with diabetes are more likely to have higher insulin resistance with obesity and have higher insulin secretory defect with severe hyperglycemia in the early period of diabetes than older populations.
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C2C12 myotubes were treated with Rg3 for 24 hours. Insulin signaling pathway proteins were examined by Western blot. Cellular adenosine triphosphate (ATP) levels and the oxygen consumption rate were measured. The protein or mRNA levels of mitochondrial complexes were evaluated by Western blot and quantitative reverse transcription polymerase chain reaction analysis.
Rg3 treatment to C2C12 cells activated the insulin signaling pathway proteins, insulin receptor substrate-1 and Akt. Rg3 increased ATP production and the oxygen consumption rate, suggesting improved mitochondrial function. Rg3 increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α, nuclear respiratory factor 1, and mitochondrial transcription factor, which are transcription factors related to mitochondrial biogenesis. Subsequent increased expression of mitochondrial complex IV and V was also observed.
Our results suggest that Rg3 improves mitochondrial function and the expression of key genes involved in mitochondrial biogenesis, leading to an improvement in insulin resistance in skeletal muscle. Rg3 may have the potential to be developed as an anti-hyperglycemic agent.
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Rebaudioside A and erythritol are nonnutritive sweeteners. There have been several studies of their glycemic effects, but the outcomes remain controversial. The purpose of this study was to evaluate the glycemic effects of rebaudioside A and erythritol as a sweetener in people with glucose intolerance.
This trial evaluated the glycemic effect after 2 weeks of consumption of rebaudioside A and erythritol as sweeteners in a pre-diabetic population. The patients were evaluated for fructosamine, fasting plasma glucose, C-peptide, insulin, and 2-hour plasma glucose before and after consumption of sweetener. The primary outcome was a change in fructosamine levels from the baseline to the end of treatment. Secondary outcomes were the changes in levels of fasting plasma glucose and 2-hour plasma glucose.
From the baseline to the end of experiment, the changes in fructosamine levels after consumption of rebaudioside A and erythritol, did not differ significantly (244.00±19.57 vs. 241.68±23.39 µmol/L,
Our study suggests that consumption of rebaudioside A and erythritol does not alter the glucose homeostasis in people with glucose intolerance.
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We compared the efficacies of vildagliptin (50 mg twice daily) relative to pioglitazone (15 mg once daily) as an add-on treatment to metformin for reducing glycosylated hemoglobin (HbA1c) levels in Korean patients with type 2 diabetes.
The present study was a multicenter, randomized, active-controlled investigation comparing the effects of vildagliptin and pioglitazone in Korean patients receiving a stable dose of metformin but exhibiting inadequate glycemic control. Each patient underwent a 16-week treatment period with either vildagliptin or pioglitazone as an add-on treatment to metformin.
The mean changes in HbA1c levels from baseline were –0.94% in the vildagliptin group and –0.6% in the pioglitazone group and the difference between the treatments was below the non-inferiority margin of 0.3%. The mean changes in postprandial plasma glucose (PPG) levels were –60.2 mg/dL in the vildagliptin group and –38.2 mg/dL in the pioglitazone group and these values significantly differed (
As an add-on to metformin, the efficacy of vildagliptin for the improvement of glycemic control is not inferior to that of pioglitazone in Korean patients with type 2 diabetes. In addition, add-on treatment with vildagliptin had beneficial effects on PPG levels, lipid profiles, and body weight compared to pioglitazone.
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The Modality of Insulin Treatment Evaluation (MOTIV) study was performed to provide real-world data concerning insulin initiation in Korean type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with oral hypoglycemic agents (OHAs).
This multicenter, non-interventional, prospective, observational study enrolled T2DM patients with inadequate glycemic control (glycosylated hemoglobin [HbA1c] ≥7.0%) who had been on OHAs for ≥3 months and were already decided to introduce basal insulin by their physician prior to the start of the study. All treatment decisions were at the physician's discretion to reflect real-world practice.
A total of 9,196 patients were enrolled, and 8,636 patients were included in the analysis (mean duration of diabetes, 8.9 years; mean HbA1c, 9.2%). Basal insulin plus one OHA was the most frequently (51.0%) used regimen. After 6 months of basal insulin treatment, HbA1c decreased to 7.4% and 44.5% of patients reached HbA1c <7%. Body weight increased from 65.2 kg to 65.5 kg, which was not significant. Meanwhile, there was significant increase in the mean daily insulin dose from 16.9 IU at baseline to 24.5 IU at month 6 (
In a real-world setting, the initiation of basal insulin is an effective and well-tolerated treatment option in Korean patients with T2DM who are failing to meet targets with OHA therapy.
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We evaluated the disease profile and clinical management, including the status of both glycemic control and complications, in patients with diabetes who were transferred to referral hospitals in Korea.
Patients referred to 20 referral hospitals in Gyeongsangnam/Gyeongsangbuk-do and Jeollanam/Jeollabuk-do with at least a 1-year history of diabetes between January and June 2011 were retrospectively reviewed using medical records, laboratory tests, and questionnaires.
A total of 654 patients were enrolled in the study. In total, 437 patients (67%) were transferred from clinics and 197 (30%) patients were transferred from hospitals. A total of 279 patients (43%) visited higher medical institutions without a written medical request. The main reason for the referral was glycemic control in 433 patients (66%). Seventy-three patients (11%) had received more than one session of diabetic education. Only 177 patients (27%) had been routinely self-monitoring blood glucose, and 146 patients (22%) were monitoring hemoglobin A1c. In addition, proper evaluations for diabetic complications were performed for 74 patients (11%). The most common complication was neuropathy (32%) followed by nephropathy (31%). In total, 538 patients (82%) had been taking oral hypoglycemic agents. A relatively large number of patients (44%) had been taking antihypertensive medications.
We investigated the clinical characteristics of diabetic patients and identified specific problems in diabetic management prior to the transfer. We also found several problems in the medical system, which were divided into three medical institutions having different roles in Korea. Our findings suggested that the relationships among medical institutions have to be improved, particularly for diabetes.
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Data regarding the prescription status of individuals with diabetes are limited. This study was an analysis of participants from the relationship between cardiovascular disease and brachial-ankle pulse wave velocity in patients with type 2 diabetes (REBOUND) Study, which was a prospective multicenter cohort study recruited from eight general hospitals in Busan, Korea. We performed this study to investigate the current status of prescription in Korean type 2 diabetic patients.
Type 2 diabetic patients aged 30 years or more were recruited and data were collected for demographics, medical history, medications, blood pressure, and laboratory tests.
Three thousands and fifty-eight type 2 diabetic patients were recruited. Mean age, duration of diabetes, and HbA1c were 59 years, 7.6 years, and 7.2%, respectively. Prevalence of hypertension was 66%. Overall, 7.3% of patients were treated with diet and exercise only, 68.2% with oral hypoglycemic agents (OHAs) only, 5.3% with insulin only, and 19.2% with both insulin and OHA. The percentage of patients using antihypertensive, antidyslipidemic, antiplatelet agents was similar as about 60%. The prevalence of statins and aspirin users was 52% and 32%, respectively.
In our study, two thirds of type 2 diabetic patients were treated with OHA only, and one fifth with insulin plus OHA, and 5% with insulin only. More than half of the patients were using each of antihypertensive, antidyslipidemic, or antiplatelet agents. About a half of the patients were treated with statins and one third were treated with aspirin.
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