Long-Term Glycaemic Durability of Early Combination Therapy Strategy versus Metformin Monotherapy in Korean Patients with Newly Diagnosed Type 2 Diabetes Mellitus.
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SUBMITTER: Yoo SJ
PROVIDER: S-EPMC8640145 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AIM:To assess the long-term clinical benefits of early combination treatment with vildagliptin-metformin vs. standard-of-care, metformin monotherapy in the ongoing VERIFY study. METHODS:We randomized 2001 participants with multi-ethnic background, aged 18-70 years, having HbA1c levels 48-58 mmol/mol (6.5-7.5%) and BMI 22-40 kg/m2 . Baseline data included HbA1c , fasting plasma glucose and homeostasis model ?-cell and insulin sensitivity. Standardized meal-tests, insulin secretion rate relative to glucose, and oral glucose insulin sensitivity were assessed in a subpopulation. RESULTS:Out of 4524 screened, data were collected from the 2001 eligible participants (53% women) across Europe (52.4%), Latin America (26.8%), Asia (17.2%), South Africa (3.1%) and Australia (0.5%). The median (interquartile range) disease duration was 3.4 (0.9, 10.2) months; mean (±SD) age 54.3±9.4 years; weight 85.5±17.5 kg and BMI 31.1±4.7 kg/m2 . Baseline HbA1c was 52±3 mmol/mol (6.9±0.3%), fasting plasma glucose 7.5±1.5 mmol/l and the median (interquartile range) of fasting insulin was 109 (75-160) mU/l. Homeostasis model ?-cell and insulin sensitivity values were 84% (60, 116) and 46% (31, 68), respectively. In those undertaking meal-tests, insulin secretion rate relative to glucose was 28±12 pmol/min/m2 /mmol/l and oral glucose insulin sensitivity was 353±57 ml/min/m2 . CONCLUSIONS:Our current, multi-ethnic, newly diagnosed VERIFY population reflects a characteristic presence of early insulin resistance in participants with increased demand for insulin associated with obesity. The VERIFY study will provide unique evidence in characterizing therapeutic intervention in a diverse population with hyperglycaemia, focusing on durability of early glycaemic control.
| S-EPMC6594102 | biostudies-literature
Project description:The treatment aims for type 2 diabetes are to prevent complications and premature mortality, and improve quality of life. Glycaemic control is central to these aims; clinical guidelines have sought to achieve this with a stepwise approach starting with lifestyle measures and metformin, adding further medications once glycated haemoglobin (HbA1c) levels rise above a predefined threshold. However, treatment intensification can be delayed when HbA1c levels increase, and HbA1c levels become inadequately controlled in many patients. Clinical inertia can result in sustained elevated levels of HbA1c; when combined with a late diagnosis, this negatively impacts patients' prognosis. Early combination therapy using medications with complementary modes of action could achieve optimal glycaemic targets and alter the course of the disease more than metformin alone. The multinational VERIFY study (clinicaltrials.gov NCT01528254) provided evidence accrued over 5 years, demonstrating the potential of early combination therapy: time to loss of glycaemic control was nearly doubled, and more than twice the number of patients experienced extended glycaemic control, with a vildagliptin-metformin combination therapy versus metformin alone. The study also showed a delay in secondary treatment failure in patients receiving the combination. Early combination therapy therefore offers a different trajectory to the stepwise approach. Translating these findings into clinical practice will require early detection and diagnosis of type 2 diabetes plus a shift in disease management. Nonetheless, the potential benefits of sustained and continuous disease control that early combination therapy offers represent the start of a new era in early diagnosis and intensive management, to achieve the treatment aims of type 2 diabetes.
| S-EPMC7547931 | biostudies-literature
Project description:Background:Cardiovascular disease is a major cause of mortality and morbidity in people with type 2 diabetes mellitus (T2DM). Studies have consistently identified dyslipidemia as an important risk factor for the development of macrovascular disease. The landmark United Kingdom Prospective Diabetes Study has shown that metformin therapy reduces cardiovascular events in overweight people with T2DM. This study investigates the effect of metformin monotherapy on serum lipid profile in statin-naïve individuals with newly diagnosed T2DM, and whether the effect, if any, is dosage-related. Methods:This cohort study enrolled individuals exceeding 20 years of age, with recent onset T2DM, who received at least 12 months of metformin monotherapy and blood tests for serum lipid at 6-month intervals. Exclusion criteria involved people receiving any additional antidiabetic medication or lipid-lowering drug therapy. Lipid-modifying effect of metformin was recorded as levels of serum triglycerides (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) measured at six month intervals. Results:The study enrolled 155 participants with a mean age of 58.6 years and average glycosylated hemoglobin A1c of 8%. After initiating metformin therapy, LDL-C was significantly reduced from 111 mg/dl to 102 mg/dL at 6 months (P < 0.001), TG was reduced from 132 mg/dl to 122 mg/dL at 12 months (P = 0.046), and HDL-C increased from 45.1 mg/dL to 46.9 mg/dL at 12 months (P = 0.02). However, increasing the dosage of metformin yielded no significant effect on its lipid-lowering efficacy. Discussion:Metformin monotherapy appreciably improves dyslipidemia in statin-naive people with T2DM. Its lipid-modifying effect may be attributable to insulin sensitization, reduction of irreversibly glycated LDL-C, and weight loss. In practice, people with dyslipidemia who are ineligible for lipid-lowering agents may benefit from metformin therapy. Moreover, previous studies report a synergistic effect between metformin and statin, which may further reduce cardiovascular events in at-risk individuals. Overall, metformin is a safe and efficacious approach to alleviate dyslipidemia in people with newly diagnosed T2DM.
| S-EPMC5899882 | biostudies-literature
Project description:Aims:The present study assessed the therapeutic effect of exenatide and metformin as the initial therapy on overweight/obese patients with newly diagnosed type 2 diabetes (T2D). Methods:The prospective, nonrandomized, interventional study enrolled a total of 230 overweight or obese patients with newly diagnosed T2D who were administrated exenatide or metformin hydrochloride for 12 weeks. Results:224/230 patients, including 106 in the exenatide group and 118 in the metformin group, completed the 12-week treatment. Both exenatide and metformin significantly decreased the HbA1c levels in overweight/obese patients with newly diagnosed T2D (all P < 0.05). The reduction in HbA1c and the proportion of patients with HbA1c?<?7.0% (53?mmol/mol) were higher in the exenatide group than in the metformin group (all P < 0.05). The exenatide treatment caused a greater decline in the body weight and BMI as compared to the metformin treatment (all P < 0.01). The exenatide treatment (??=?0.41, P < 0.01) and baseline HbA1c level (??=?-0.84, P < 0.01) were independent influencing factors for the decrease in HbA1c level. Conclusions:For an initial therapy in overweight/obese patients with newly diagnosed T2D, exenatide causes a better glycemic control than metformin. This trial is registered with NCT03297879.
| S-EPMC5735665 | biostudies-literature
Project description: Not available
| S-EPMC7386876 | biostudies-literature
Project description:To evaluate the efficacy, tolerability, and effects on behavior and psychosocial functioning of lamotrigine monotherapy in children with newly diagnosed typical absence seizures.Children meeting enrollment criteria (n=54) received a confirmatory 24-h ambulatory electroencephalogram (EEG) and then entered a Escalation Phase of up to 20-weeks during which lamotrigine was titrated until seizures were controlled or maximum dose (10.2mg/kg) was reached. Seizure freedom was assessed by diary review and clinic hyperventilation (clinic HV) and then confirmed by EEG with hyperventilation (HV/EEG). Patients who maintained seizure freedom for two consecutive weekly visits were entered into the Maintenance Phase (n=30). Diary, clinic HV, and HV/EEG data were supplemented with 24-h ambulatory EEG at baseline and the ends of the Escalation and Maintenance Phases. Health outcome assessments were completed at screening and at the end of the Maintenance Phase.By the end of the Escalation Phase, seizure-free rates (responders) were 59% by seizure diary (n=51), 56% by HV/EEG (n=54) (primary endpoint), and 49% by 24-h ambulatory EEG (n=49). During the Maintenance Phase, 89% (week 24) and 86% (week 32) remained seizure free by diary (n=28), 78% by clinic HV (n=27), and 81% by 24-h ambulatory EEG (n=26). Seizure freedom was first observed beginning at the fifth week of the Escalation Phase. The most frequent adverse events were headache and cough. Health outcome scores were either improved or unchanged at the end of the Maintenance Phase.Lamotrigine monotherapy results in complete seizure freedom in a substantial number of children with typical absence seizures. Lamotrigine was well tolerated in this study.
| S-EPMC3240743 | biostudies-literature
Project description:BackgroundDiabetes mellitus (DM) is a well-known risk factor for tuberculosis (TB). Metformin, which is an essential anti-diabetic drug, has been shown to exhibit anti-TB effects in patients with DM. Its effect on preventing the development of TB among patients who are newly diagnosed with DM remains unclear.MethodsThis was a retrospective cohort study using the claims database of the Korean Health Insurance Review and Assessment Service. The study population included patients who were newly diagnosed with type 2 DM and who were treated with anti-diabetic drugs between 1 January 2003 and 31 March 2011. A patient was defined as a metformin user if he/she had taken metformin for more than 28 days within 6 months since cohort entry, and as a metformin non-user if he/she had never been treated with metformin. The development of TB within 2 years after the index date was compared by Cox proportional hazard regression models between metformin users and 1:1 propensity score (PS)-matched non-users.ResultsAmong 76,973 patients who were newly diagnosed with type 2 DM, 13,396 were classified as metformin users, 52,736 were classified as metformin non-users, and 10,841 were excluded from the final analysis. PS-matched Cox proportional hazard regression models revealed that metformin use was not associated overall with the prevention of TB development (HR 1.17; 95% CI 0.75-1.83; P = 0.482). There was a trend, however, towards a reduction in the development of TB among patients taking a higher cumulative dose of metformin. Patients who were in the highest quartile (Q4) of cumulative metformin dose had only a 10% risk of developing TB compared to metformin non-users. In contrast, during the early phases of metformin treatment, patients in the second quartile (Q2) of cumulative metformin use had a higher risk of developing TB than patients in the first quartile (Q1).ConclusionsOnly the highest cumulative doses of metformin were protective against the development of TB among patients who were newly diagnosed with type 2 DM; lower cumulative doses of metformin did not appear to reduce the incidence of active TB infection.
| S-EPMC8464151 | biostudies-literature
Project description:This study was designed to evaluate the effect of Korean red ginseng (KRG) supplementation on glucose control in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or newly diagnosed type 2 diabetes mellitus (T2DM). The study was a 12-week randomized, double-blinded, placebo-controlled (5?g of KRG [n=21] or placebo [n=20] in tablet form) trial. Glucose-related biomarkers, including serum and whole blood levels of glucose, insulin, and C-peptide, were measured by 2-h oral glucose tolerance tests (OGTTs) at baseline and after the 12-week intervention. After the intervention, the test group showed a significant decrease in serum levels of glucose at 30?min (-22.24±10.77?mg/dL) and whole blood levels of glucose at 30?min (-17.52±5.22?mg/dL). In addition, the test group tended to have lower whole blood levels of glucose at 0?min and glucose area under curve (AUC). However, the placebo group did not show any changes in blood glucose-related indices. The changes (difference from baseline) in serum glucose levels at 30?min, whole blood glucose levels at 60?min, and glucose AUC during OGTTs in the test group exhibited a tendency toward a decrease from those in the placebo group. There were significant decreases or trends toward a decrease in both serum insulin and C-peptide concentrations at most time intervals in the test group. In conclusion, KRG supplementation (5?g/day) may be beneficial for controlling serum and whole blood glucose levels compared with placebo among patients with IFG, IGT, or T2DM.
| S-EPMC3901349 | biostudies-literature
Project description:Rationale: Sleep-disordered breathing (SDB) is associated with increased risk of adverse pregnancy outcomes, including gestational diabetes mellitus (GDM). GDM is a significant cause of maternal and infant morbidities. Assessing these risk factors concurrently may facilitate both the identification of women at GDM risk and the initiation of GDM prevention strategies.Objectives: To investigate whether SDB events, including SDB in rapid eye movement (REM) sleep and other sleep parameters, are associated with increased risk of GDM and to evaluate the performance of the models investigating associations between breathing and sleep parameters and GDM risk.Methods: In this case-control study, 46 women with newly diagnosed GDM and 46 healthy control subjects, who were individually matched for age, gestational age, body mass index, race, and parity, completed overnight polysomnographic studies and sleep questionnaires after being screened for GDM during the late-second to mid-third trimesters. Conditional logistic regression analysis was used to identify models investigating associations between risk factors and GDM risk. The Bayesian information criterion (BIC) was employed to compare models; the model with the lowest BIC is preferred.Results: Obstructive sleep apnea (OSA; defined as an apnea-hypopnea index [AHI] >5 events/h) was present in 22% of subjects with GDM and 9% of control subjects (P < 0.001). Women with OSA had a higher GDM risk (odds ratio [OR], 4.71; 95% confidence interval [CI], 1.05-21.04). In individual models, GDM risk was also significantly higher among women with higher overall AHI (events/h OR, 1.81; 95% CI, 1.01-3.27), higher AHI in REM (events/h OR, 2.09; 95% CI, 1.02-4.31), higher oxygen desaturation index greater than or equal to 4% (ODI4; events/h OR, 2.21; 95% CI, 1.03-4.73), and higher Sleep Apnea Symptom Score (OR, 2.72; 95% CI, 1.11-6.69). The percentage of non-REM sleep was significantly associated with decreased risk of GDM (percentage of non-REM sleep OR, 0.88; 95% CI, 0.78-0.99). The BIC supports the conclusion that there is a strong association between AHI in REM and GDM risk compared with the other significant models.Conclusions: SDB events, including REM-related OSA, are linked to increased GDM risk. GDM risk is also influenced by intercorrelated sleep variables.
| S-EPMC7258422 | biostudies-literature
Project description:Six oral medication classes have been approved by the Food and Drug Administration for the treatment of type 2 diabetes. Although all of these agents effectively lower blood glucose, the evidence supporting their impact on other clinical events is variable. There also are substantial cost differences between agents. We aimed to evaluate temporal trends in the use of specific drugs for the initial management of type 2 diabetes and to estimate the economic consequences of non-recommended care.We studied a cohort of 254,973 patients, aged 18 to 100 years, who were newly initiated on oral hypoglycemic monotherapy between January 1, 2006, and December 31, 2008, by using prescription claims data from a large pharmacy benefit manager. Linear regression models were used to assess whether medication initiation patterns changed over time. Multivariate logistic regression models were constructed to identify independent predictors of receiving initial therapy with metformin. We then measured the economic consequences of prescribing patterns by drug class for both patients and the insurer.Over the course of the study period, the proportion of patients initially treated with metformin increased from 51% to 65%, whereas those receiving sulfonylureas decreased from 26% to 18% (P<.001 for both). There was a significant decline in the use of thiazolidinediones (20.1%-8.3%, P<.001) and an increase in prescriptions for dipeptidyl peptidase-4 inhibitors (0.4%-7.3%, P<.001). Younger patients, women, and patients receiving drug benefits through Medicare were least likely to initiate treatment with metformin. Combined patient and insurer spending for patients who were initiated on alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, or dipeptidyl peptidase-4 inhibitors was $677 over a 6-month period compared with $116 and $118 for patients initiated on metformin or a sulfonylurea, respectively, a cost difference of approximately $1120 annually per patient.Approximately 35% of patients initiating an oral hypoglycemic drug did not receive recommended initial therapy with metformin. These practice patterns also have substantial implications for health care spending.
| S-EPMC4347833 | biostudies-other