Dataset Information

Efficacy of vildagliptin for prevention of postpartum diabetes in women with a recent history of insulin-requiring gestational diabetes: A phase II, randomized, double-blind, placebo-controlled study.

ABSTRACT: OBJECTIVE:Women with insulin-requiring gestational diabetes mellitus (GDM) are at high risk of developing diabetes within a few years postpartum. We implemented this phase II study to test the hypothesis that vildagliptin, a dipeptidyl peptidase-4 inhibitor, is superior to placebo in terms of reducing the risk of postpartum diabetes. METHODS:Women with insulin-requiring GDM were randomized to either placebo or 50 mg vildagliptin twice daily for 24 months followed by a 12-month observation period (EudraCT: 2007-000634-39). Both groups received lifestyle counseling. The primary efficacy outcomes were the diagnosis of diabetes (American Diabetes Association (ADA) criteria) or impaired fasting glucose (IFG)/impaired glucose tolerance (IGT). RESULTS:Between 2008 and 2015, 113 patients (58 vildagliptin, 55 placebo) were randomized within 2.2-10.4 (median 8.6) months after delivery. At the interim analysis, nine diabetic events and 28 IFG/IGT events had occurred. Fifty-two women withdrew before completing the treatment phase. Because of the low diabetes rate, the study was terminated. Lifestyle adherence was similar in both groups. At 24 months, the cumulative probability of postpartum diabetes was 3% and 5% (hazard ratio: 1.03; 95% confidence interval: 0.15-7.36) and IFG/IGT was 43% and 22% (hazard ratio: 0.55; 95% confidence interval: 0.26-1.19) in the placebo and vildagliptin groups, respectively. Vildagliptin was well tolerated with no unexpected adverse events. CONCLUSIONS:The study did not show significant superiority of vildagliptin over placebo in terms of reducing the risk of postpartum diabetes. However, treatment was safe and suggested some improvements in glycemic control, insulin resistance, and ?-cell function. The study identified critical issues in performing clinical trials in the early postpartum period in women with GDM hampering efficacy assessments. With this knowledge, we have set a basis for which properly powered trials could be performed in women with recent GDM. TRIAL REGISTRATION NUMBER AT CLINICALTRIALS.GOV: NCT01018602.

SUBMITTER: Hummel S

PROVIDER: S-EPMC5869734 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy of vildagliptin for prevention of postpartum diabetes in women with a recent history of insulin-requiring gestational diabetes: A phase II, randomized, double-blind, placebo-controlled study.

Hummel Sandra S Beyerlein Andreas A Pfirrmann Markus M Hofelich Anna A Much Daniela D Hivner Susanne S Bunk Melanie M Herbst Melanie M Peplow Claudia C Walter Markus M Kohn Denise D Hummel Nadine N Kratzsch Jürgen J Hummel Michael M Füchtenbusch Martin M Hasford Joerg J Ziegler Anette-G AG

Molecular metabolism 20180103

<h4>Objective</h4>Women with insulin-requiring gestational diabetes mellitus (GDM) are at high risk of developing diabetes within a few years postpartum. We implemented this phase II study to test the hypothesis that vildagliptin, a dipeptidyl peptidase-4 inhibitor, is superior to placebo in terms of reducing the risk of postpartum diabetes.<h4>Methods</h4>Women with insulin-requiring GDM were randomized to either placebo or 50 mg vildagliptin twice daily for 24 months followed by a 12-month obs ...[more]

PMID: 29396374

Similar Datasets

Project description:ObjectiveTo assess patterns and predictors of postpartum diabetes screening in a commercially insured, geographically and sociodemographically diverse sample of women with gestational diabetes mellitus.MethodsUsing commercial insurance claims (2000-2012) from all 50 states, we conducted a retrospective cohort study in 447,556 women with at least one delivery and continuous enrollment 1 year before and after delivery. We identified women with a gestational diabetes mellitus pregnancy and examined postpartum diabetes screening type and timing and performed logistic regression to identify screening predictors.ResultsGestational diabetes mellitus was diagnosed in 32,253 (7.2%) women during the study timeframe. Three fourths received no screening within 1 year postpartum. Rates of recommended 75-g oral glucose tolerance testing within 6-12 weeks were low but increased over time (27 [2%] in 2001 compared with 249 [7%] in 2011, adjusted odds ratio [OR] 3.1, 95% confidence interval [CI] 2.0-47). Among women screened, those in the Northeast (19%) and South (18%) were least likely to receive a 75-g oral glucose tolerance test within 0-12 weeks (adjusted OR 0.4 for each, CI 0.4-0.5) compared with the West (36%). Asian women were most likely to receive any screening (18%; adjusted OR 1.5, CI 1.3-1.6) compared with white women (12%). Black women were most likely to receive hemoglobin A1c (21%; adjusted OR 2.0, CI 1.3-3.2) compared with white women (11%). Antepartum antiglycemic medication (21%; adjusted OR 2.1, CI 2.0-2.3) or visit to a nutritionist-diabetes educator (19%; adjusted OR 1.6, CI 1.4-1.7) or endocrinologist (23%; adjusted OR 1.7, CI 1.6-1.9) predicted screening within 12 weeks postpartum.ConclusionPostpartum diabetes screening remains widely underused among commercially insured women with gestational diabetes mellitus. Differences in screening by geography, race, and antepartum care can inform health system and public health interventions to increase diabetes detection in this high-risk population.

Project description:Women who develop gestational diabetes mellitus (GDM) have an increased risk for the development of type 2 diabetes. Despite this "window of opportunity," few intervention studies have targeted postpartum women with a history of GDM. We sought perspectives of women with a history of GDM to identify a) barriers and facilitators to healthy lifestyle changes postpartum, and b) specific intervention approaches that would facilitate participation in a postpartum lifestyle intervention program.We used mixed methods to gather data from women with a prior history of GDM, including focus groups and informant interviews. Analysis of focus groups relied on grounded theory and used open-coding to categorize data by themes, while frequency distributions were used for the informant interviews.Of 38 women eligible to participate in focus groups, only ten women were able to accommodate their schedules to attend a focus group and 15 completed informant interviews by phone. We analyzed data from 25 women (mean age 35, mean pre-pregnancy BMI 28, 52% Caucasian, 20% African American, 12% Asian, 8% American Indian, 8% refused to specify). Themes from the focus groups included concern about developing type 2 diabetes, barriers to changing diet, and barriers to increasing physical activity. In one focus group, women expressed frustration about feeling judged by their physicians during their GDM pregnancy. Cited barriers to lifestyle change were identified from both methods, and included time and financial constraints, childcare duties, lack of motivation, fatigue, and obstacles at work. Informants suggested facilitators for lifestyle change, including nutrition education, accountability, exercise partners/groups, access to gyms with childcare, and home exercise equipment. All focus group and informant interview participants reported access to the internet, and the majority expressed interest in an intervention program delivered primarily via the internet that would include the opportunity to work with a lifestyle coach.Time constraints were a major barrier. Our findings suggest that an internet-based lifestyle intervention program should be tested as a novel approach to prevent type 2 diabetes in postpartum women with a history of GDM.

Project description:Women with gestational diabetes mellitus (GDM) have a substantial risk of subsequently developing type 2 diabetes. This risk may be mitigated by engaging in healthy eating, physical activity, and weight loss when indicated. Since postpartum depressive symptoms may impair a woman's ability to engage in lifestyle changes, we sought to identify factors associated with depressive symptoms in the early postpartum period among women with recent GDM. The participants are part of the baseline cohort of the TEAM GDM (Taking Early Action for Mothers with Gestational Diabetes Mellitus) study, a one-year randomized trial of a lifestyle intervention program for women with a recent history of GDM, conducted in Boston, Massachusetts between June 2010 and September 2012. We administered the Edinburgh Postnatal Depression Scale (EPDS) at 4-15 weeks postpartum to women whose most recent pregnancy was complicated by GDM (confirmed by laboratory data or medical record review). An EPDS score ?9 indicated depressive symptoms. We measured height and thyroid stimulating hormone, and administered a questionnaire to collect demographic data and information about breastfeeding and sleep. We calculated body mass index (BMI) using self-reported pre-pregnancy weight and measured height. We reviewed medical records to obtain data about medical history, including history of depression, mode of delivery, and insulin use during pregnancy. We conducted bivariable analyses to identify correlates of postpartum depressive symptoms, and then modeled the odds of postpartum depressive symptoms using multivariable logistic regression. Our study included 71 women (mean age 33 years ± 5; 59 % White, 28 % African-American, 13 % Asian, with 21 % identifying as Hispanic; mean pre-pregnancy BMI 30 kg/m(2) ± 6). Thirty-four percent of the women scored ?9 on the EPDS at the postpartum visit. In the best fit model, factors associated with depressive symptoms at 6 weeks postpartum included cesarean delivery (aOR 4.32, 95 % CI 1.46, 13.99) and gestational weight gain (aOR 1.21 [1.02, 1.46], for each additional 5 lbs gained). Use of insulin during pregnancy, breastfeeding, personal history of depression, and lack of a partner were not retained in the model. Identifying factors associated with postpartum depression in women with GDM is important since depression may interfere with lifestyle change efforts in the postpartum period. In this study, cesarean delivery and greater gestational weight gain were correlated with postpartum depressive symptoms among women with recent GDM (Clinicaltrials.gov NCT01158131).

Project description:BackgroundNew-onset diabetes mellitus after transplantation (NODAT), a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c) values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT.Methods/designThis study is a randomized, placebo-controlled, double-blind, prospective phase II trial. Using the results of routinely performed oral glucose tolerance tests (OGTT) in stable renal transplant patients at our center, we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl (11.1 mmol/l). They are randomized to receive either 50 mg vildagliptin or placebo once daily. A total of 32 patients with newly diagnosed NODAT will be included. The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group. Secondary endpoints include changes in HbA1c and fasting plasma glucose (FPG). The safety of vildagliptin in renal transplant patients will be assessed by the number of symptomatic hypoglycemic episodes (glucose <72 mg/dl or 4 mmol/l), the number of adverse events, and possible medication-associated side-effects.DiscussionNODAT is a severe complication after kidney transplantation. Few trials have assessed the safety and efficacy of antidiabetic drugs for these patients. The purpose of this study is to assess the safety and efficacy of vildagliptin in renal transplant patients with NODAT.Trial registrationClinicalTrials.gov NCT00980356.

Project description:BackgroundWomen with a history of gestational diabetes mellitus (GDM) have a 7-fold higher risk of developing type 2 diabetes (T2D). It is estimated that 20-50% of women with GDM history will progress to T2D within 10 years after delivery. Intensive lactation could be negatively associated with this risk, but the mechanisms behind a protective effect remain unknown.MethodsIn this study, we utilized a prospective GDM cohort of 1010 women without T2D at 6-9 weeks postpartum (study baseline) and tested for T2D onset up to 8 years post-baseline (n=980). Targeted metabolic profiling was performed on fasting plasma samples collected at both baseline and follow-up (1-2 years post-baseline) during research exams in a subset of 350 women (216 intensive breastfeeding, IBF vs. 134 intensive formula feeding or mixed feeding, IFF/Mixed). The relationship between lactation intensity and circulating metabolites at both baseline and follow-up were evaluated to discover underlying metabolic responses of lactation and to explore the link between these metabolites and T2D risk.ResultsWe observed that lactation intensity was strongly associated with decreased glycerolipids (TAGs/DAGs) and increased phospholipids/sphingolipids at baseline. This lipid profile suggested decreased lipogenesis caused by a shift away from the glycerolipid metabolism pathway towards the phospholipid/sphingolipid metabolism pathway as a component of the mechanism underlying the benefits of lactation. Longitudinal analysis demonstrated that this favorable lipid profile was transient and diminished at 1-2 years postpartum, coinciding with the cessation of lactation. Importantly, when stratifying these 350 women by future T2D status during the follow-up (171 future T2D vs. 179 no T2D), we discovered that lactation induced robust lipid changes only in women who did not develop incident T2D. Subsequently, we identified a cluster of metabolites that strongly associated with future T2D risk from which we developed a predictive metabolic signature with a discriminating power (AUC) of 0.78, superior to common clinical variables (i.e., fasting glucose, AUC 0.56 or 2-h glucose, AUC 0.62).ConclusionsIn this study, we show that intensive lactation significantly alters the circulating lipid profile at early postpartum and that women who do not respond metabolically to lactation are more likely to develop T2D. We also discovered a 10-analyte metabolic signature capable of predicting future onset of T2D in IBF women. Our findings provide novel insight into how lactation affects maternal metabolism and its link to future diabetes onset.Trial registrationClinicalTrials.gov NCT01967030 .

Dataset Information

Efficacy of vildagliptin for prevention of postpartum diabetes in women with a recent history of insulin-requiring gestational diabetes: A phase II, randomized, double-blind, placebo-controlled study.

Publications

Efficacy of vildagliptin for prevention of postpartum diabetes in women with a recent history of insulin-requiring gestational diabetes: A phase II, randomized, double-blind, placebo-controlled study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets