Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension.

BACKGRUOUND: This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. METHODS: In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). RESULTS: Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, -0.65% and -0.55%; 95% confidence interval [CI], -0.79 to -0.51 and -0.71 to -0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of ß-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group. CONCLUSION: Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Efficacy and safety of evogliptin monotherapy in patients with type 2 diabetes and moderately elevated glycated haemoglobin levels after diet and exercise.

AIMS: To evaluate the efficacy and safety of evogliptin, a newly developed dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes (T2D) inadequately controlled by diet and exercise. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled, parallel-group, multicentre, phase III study, 160 patients with T2D were assigned to either evogliptin 5 mg or placebo for 24 weeks. The primary endpoint was the mean change in glycated haemoglobin (HbA1c) from baseline to week 24. RESULTS: The mean baseline HbA1c levels were similar in the evogliptin and the placebo groups (7.20% ± 0.56% vs 7.20% ± 0.63%, respectively). At week 24, evogliptin significantly reduced HbA1c levels from baseline compared with placebo (-0.23% vs 0.05%, respectively, P < .0001). Additionally, the proportion of patients achieving HbA1c <6.5% was significantly higher in the evogliptin group than in the placebo group (33.3% vs 15.2%; P = .008). The overall incidence of adverse events, including hypoglycaemia, was similar in the 2 groups. CONCLUSIONS: In this 24-week study, once-daily evogliptin monotherapy significantly improved glycaemic control and was well tolerated in patients with T2D.

Correlations between Glucagon Stimulated C-peptide Levels and Microvascular Complications in Type 2 Diabetes Patients.

BACKGROUND: This study aimed to investigate whether stimulated C-peptide is associated with microvascular complications in type 2 diabetes mellitus (DM). METHODS: A cross-sectional study was conducted in 192 type 2 diabetic patients. Plasma basal C-peptide and stimulated C-peptide were measured before and 6 minutes after intravenous injection of 1 mg glucagon. The relationship between C-peptide and microvascular complications was statistically analyzed. RESULTS: In patients with retinopathy, basal C-peptide was 1.9±1.2 ng/mL, and stimulated C-peptide was 2.7±1.6 ng/mL; values were significantly lower compared with patients without retinopathy (P=0.031 and P=0.002, respectively). In patients with nephropathy, basal C-peptide was 1.6±0.9 ng/mL, and stimulated C-peptide was 2.8±1.6 ng/mL; values were significantly lower than those recorded in patients without nephropathy (P=0.020 and P=0.026, respectively). Stimulated C-peptide level was associated with increased prevalence of microvascular complications. Age-, DM duration-, and hemoglobin A1c-adjusted odds ratios for retinopathy in stimulated C-peptide value were 4.18 (95% confidence interval [CI], 1.40 to 12.51) and 3.35 (95% CI, 1.09 to 10.25), respectively. The multiple regression analysis between nephropathy and C-peptide showed that stimulated C-peptide was statistically correlated with nephropathy (P=0.03). CONCLUSION: In patients with type 2 diabetes, the glucagon stimulation test was a relatively simple method of short duration for stimulating C-peptide response. Stimulated C-peptide values were associated with microvascular complications to a greater extent than basal C-peptides.

Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients.

BACKGROUND: Recent studies have revealed that C-peptide induces smooth muscle cell proliferation and causes human atherosclerotic lesions in diabetic patients. The present study was designed to examine whether the basal C-peptide levels correlate with cardiovascular risk in type 2 diabetes mellitus (T2DM) patients. METHODS: Data was obtained from 467 patients with T2DM from two institutions who were followed for four years. The medical findings of all patients were reviewed, and patients with creatinine >1.4 mg/dL, any inflammation or infection, hepatitis, or type 1 DM were excluded. The relationships between basal C-peptide and other clinical values were statistically analyzed. RESULTS: A simple correlation was found between basal C-peptide and components of metabolic syndrome (MS). Statistically basal C-peptide levels were significantly higher than the three different MS criteria used in the present study, the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program's (NCEP's), World Health Organization (WHO), and the International Diabetes Federation (IDF) criteria (NCEP-ATP III, P=0.001; IDF, P<0.001; WHO, P=0.029). The multiple regression analysis between intima-media thickness (IMT) and clinical values showed that basal C-peptide significantly correlated with IMT (P=0.043), while the analysis between the 10-year coronary heart disease risk by the United Kingdom Prospective Diabetes Study risk engine and clinical values showed that basal C-peptide did not correlate with IMT (P=0.226). CONCLUSION: Basal C-peptide is related to cardiovascular predictors (IMT) of T2DM, suggesting that basal C-peptide does provide a further indication of cardiovascular disease.

The comparison of (131)I whole-body scans on the third and tenth day after (131)I therapy in patients with well-differentiated thyroid cancer: preliminary report.

OBJECTIVE: The purpose of the present study was to evaluate the clinical usefulness of the delayed post-therapeutic (131)I scan in patients with well-differentiated thyroid cancer by comparing the early scanned images with the delayed images. METHODS: A total of 81 patients (female:male = 67:14; age 52 ± 13 years) with well-differentiated thyroid cancer who underwent scans the third and tenth day after (131)I treatment were included in this study. The therapeutic dose ranged from 3.7 GBq (100 mCi) to 7.4 GBq (200 mCi). The early and delayed scan images were visually analyzed and the thyroid remnant-to-background uptake ratio (RBR) and the lesion-to-background uptake ratio (LBR) of metastatic lesions were calculated. RESULTS: Of the 81 patients, 5 lesions (2 lung lesions, 2 cervical lymph node lesions, and one thyroid remnant) in 4 patients (5%) were additionally found on the delayed scans, which were not identified on the early scans. Of 8 patients with high serum thyroglobulin (Tg) and negative finding on the early scan, the delayed scan identified additional lesions in 3 patients (38%). Visual analysis scores significantly decreased for both thyroid remnants and metastatic lesions on the delayed scan (p < 0.001 for all). Diffuse hepatic uptake was visualized in 86% of all patients on the delayed scan, while only 6% of the patients on the early scan (p < 0.001). The RBRs of both scans were compared in 59 patients, and the LBRs were compared in 8 patients with 23 lesions. The mean RBR and LBR on the delayed scan (8.0 ± 7.6 and 5.4 ± 5.2, respectively) were significantly lower than those on the early scan (12.0 ± 10.8 and 10.8 ± 7.6, respectively; p = 0.02 and p = 0.001, respectively). CONCLUSIONS: The (131)I-avid lesions on the early scan were more easily detected by visual analysis and had higher uptake ratios than those on the delayed scan. However, for patients with high serum Tg and negative finding on the early scan, the delayed scan was helpful in identifying additional (131)I-avid lesions.