A Randomized Controlled Trial of R-Form Verapamil Added to Ongoing Metformin Therapy in Patients with Type 2 Diabetes.

CONTEXT: There is a medical need for effective insulin-independent antidiabetic drugs that can promote pancreatic ß-cell function and have a low risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients. R-form verapamil (R-Vera), which is able to enhance the survival of ß-cells and has higher cardiovascular safety margin compared with racemic verapamil, was developed as a novel approach for T2DM treatment. OBJECTIVE: This randomized, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of 3 dosages of R-Vera added to ongoing metformin therapy in T2DM patients who had inadequate glycemic control on metformin alone. METHODS: Participants were randomly assigned in an equal ratio to receive R-Vera 450, 300, or 150 mg per day, or matching placebo, in combination with metformin. The primary endpoint was change in hemoglobin A1c (HbA1c) after 12 weeks of treatment. RESULTS: A total of 184 eligible participants were randomized to receive either R-Vera or placebo plus metformin. At week 12, significant reductions in HbA1c were observed for R-Vera 300 mg/day (-0.36, P = 0.0373) and 450 mg/day (-0.45, P = 0.0098) compared with placebo. The reduction in HbA1c correlated with decreasing fasting plasma glucose levels and improved HOMA2-ß score. Treatment with R-Vera was well tolerated with no hypoglycemic episodes occurring during the trial. CONCLUSION: Addition of R-Vera twice daily to ongoing metformin therapy significantly improved glycemic control in T2DM patients. The favorable efficacy and safety profile of R-Vera 300 mg/day can be considered as the appropriate dose for clinical practice.

Use and effectiveness of dapagliflozin in patients with type 2 diabetes mellitus: a multicenter retrospective study in Taiwan.

AIMS/INTRODUCTION: To investigate the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) who initiated dapagliflozin in real-world practice in Taiwan. MATERIALS AND METHODS: In this multicenter retrospective study, adult patients with T2DM who initiated dapagliflozin after May 1st 2016 either as add-on or switch therapy were included. Changes in clinical and laboratory parameters were evaluated at 3 and 6 months. Baseline factors associated with dapagliflozin response in glycated hemoglobin (HbA1c) were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 1,960 patients were eligible. At 6 months, significant changes were observed: HbA1c by -0.73% (95% confidence interval [CI] -0.80, -0.67), body weight was -1.61 kg (95% CI -1.79, -1.42), and systolic/diastolic blood pressure by -3.6/-1.4 mmHg. Add-on dapagliflozin showed significantly greater HbA1c reduction (-0.82%) than switched therapy (-0.66%) (p = 0.002). The proportion of patients achieving HbA1c <7% target increased from 6% at baseline to 19% at Month 6. Almost 80% of patients experienced at least 1% reduction in HbA1c, and 65% of patients showed both weight loss and reduction in HbA1c. Around 37% of patients had at least 3% weight loss. Multivariate logistic regression analysis indicated patients with higher baseline HbA1c and those who initiated dapagliflozin as add-on therapy were associated with a greater reduction in HbA1c. CONCLUSIONS: In this real-world study with the highest patient number of Chinese population to date, the use of dapagliflozin was associated with significant improvement in glycemic control, body weight, and blood pressure in patients with T2DM. Initiating dapagliflozin as add-on therapy showed better glycemic control than as switch therapy.

Post-marketing surveillance study of valsartan/amlodipine combination in Taiwanese hypertensive patients.

AIMS: To assess safety and efficacy of valsartan/amlodipine combination in hypertensive Taiwanese patients. METHODS: This 12-week, multi-center, prospective, observational, post-marketing study enrolled 1029 patients to receive valsartan/amlodipine combination alone or as add-on to other antihypertensives. Efficacy was evaluated by blood pressure (BP) control rate (in mmHg; non-diabetics, < 140/90; diabetics, < 130/80) at Week 12 and BP-lowering ability at Weeks 4 and 12. Additionally, responder rate (sitting-SBP < 140 for baseline SBP ≥ 140 or sitting-DBP < 90 for baseline DBP ≥ 90, or SBP reduction > 20 or DBP reduction > 10 from baseline) was determined. MAJOR FINDINGS: Adverse events (AEs) were reported in 12.15% patients; dizziness, cough, and peripheral edema were the most commonly reported AEs. Overall BP control rate was 48.27%. Greater BP reduction was noted at Week 12 than at Week 4 between all groups and subgroups. Greater SBP/DBP reduction was observed in patients with stage 2 hypertension than stage 1 hypertension at baseline. The overall responder rate was 78.52%. Subgroup analysis showed greater BP reduction in non-diabetics than diabetics; only SBP reduction reached statistical significance (- 13.7 [18.3] vs. - 10.7 [17.4] mmHg; p < 0.0093). PRINCIPAL CONCLUSION: Valsartan/amlodipine combination was well tolerated, with no safety concerns identified and an effective treatment option for hypertensive Taiwanese patients.

Noninvasive blood glucose monitoring using the optical signal of pulsatile microcirculation: a pilot study in subjects with diabetes.

OBJECTIVE: The objective of this study was to determine the conditions for optimizing measurements obtained with a noninvasive blood glucose monitor using the optical signal of pulsatile microcirculation (OSPM) in both prediabetic and diabetic subjects receiving medication. RESEARCH DESIGN AND METHODS: Eighteen subjects (3 prediabetic, 15 diabetic) aged 61.8 [15.9] years (mean [S.D.]) were studied. OSPM was the pulsatile component (P) of the signal obtained and analyzed by a blood glucose monitor. The measurement was calibrated to the fingerstick meter for each subject for personal calibration. Data were obtained from all subjects using both meters. RESULTS: A total of 179 data pairs were measured and analyzed. The validity of the position of the tested finger was assessed using the position criterion, which resulted in the removal of 38 data pairs. The criterion for the intensity of the P signal was satisfied by 141 data pairs, with nonconforming data (with a much lower P signal) mainly occurring below 26 degrees C. A total of 113 data points passed both criteria, and 100% of them fell within Zones A and B of the Clarke error grid. Data in Zones A and B exhibited a linear relationship (r=.81; slope=0.82; intercept=28.0) between noninvasive and fingerstick measurements. CONCLUSIONS: Environmental temperature has the greatest influence on the capability of the OSPM technique to monitoring blood glucose concentration, which is subject dependent. The position of the tested finger is the second major factor, hence a carefully designed finger adaptor is essential.

Adrenal insufficiency combined with gastric cardia ulcer due to herpes simplex virus type 1 infection.

Adrenal insufficiency combined with gastric ulcer due to herpes simplex virus (HSV) infection is a very unusual condition. A 75-year-old woman suffered from a 4-day history of poor appetite, constipation, dysuria, severe headache, generalized pain and malaise. Hyponatremia was noted. Escherichia coli infection was identified from urine culture. Poor pituitary-adrenal axis response to hyponatremia and infection, as well as a history of intermittent treatment with steroids, led to a diagnosis of iatrogenic tertiary adrenal insufficiency. During hospitalization, the patient passed tarry stools. In addition to an antral ulcer, panendoscopy revealed an ulcer in the gastric cardia with a clean base and irregular margins. Biopsy of the cardia demonstrated multinucleated giant cells in the stratified squamous epithelium. Polymerase chain reaction studies confirmed HSV type 1 infection. In patients suffering from gastric cardia ulcer, the possibility of herpes infection must be considered, especially when complicated by steroid treatment or misuse. Because herpes infection in the squamous epithelium is self-limiting, practitioners should be aware of it, so that overtreatment can be avoided.