Study protocol: Behavioral economics and self-determination theory to change diabetes risk (BEST Change).

BACKGROUND: The Diabetes Prevention Program (DPP) and metformin can prevent or delay the onset of type 2 diabetes mellitus (T2DM) among patients with prediabetes. Yet, even when these evidence-based strategies are accessible and affordable, uptake is low. Thus, there is a critical need for effective, scalable, and sustainable approaches to increase uptake and engagement in these interventions. METHODS: In this randomized controlled trial, we will test whether financial incentives and automated messaging to promote autonomous motivation for preventing T2DM can increase DPP participation, metformin use, or both among adults with prediabetes. Participants (n = 380) will be randomized to one of four study arms. Control Arm participants will receive usual care and educational text messages about preventing T2DM. Incentives Arm participants will receive the Control Arm intervention plus financial incentives for DPP participation or metformin use. Tailored Messages Arm participants will receive the Control Arm intervention plus tailored messages promoting autonomous motivation for preventing T2DM. Combined Arm participants will receive the Incentives Arm and Tailored Messages Arm interventions plus messages to increase the personal salience of financial incentives. The primary outcome is change in hemoglobin A1c from baseline to 12 months. Secondary outcomes are change in body weight, DPP participation, and metformin use. DISCUSSION: If effective, these scalable and sustainable approaches to increase patient motivation to prevent T2DM can be deployed by health systems, health plans, and employers to help individuals with prediabetes lower their risk for developing T2DM.

Liraglutida 3 mg para o tratamento de pacientes com obesidade e IMC acima de 35 kg/m², pré-diabetes e alto risco de doença cardiovascular / Liraglutide 3 mg for the treatment of patients with obesity and BMI above 35 kg/m², pre-diabetes and high risk of cardiovascular disease

INTRODUÇÃO: A obesidade é uma doença multifatorial altamente hereditária que representa um grande impacto na saúde humana. Ela pode ser definida como o acúmulo anormal ou excessivo de gordura, de forma regionalizada, generalizada ou ambas, que apresenta risco à saúde. Um índice de massa corporal (IMC) acima de 30 é considerado como obesidade, a qual pode ser classificada como leve (grau I; IMC ≥ 30 kg/m2 ), moderada (grau II; IMC ≥ 35 kg/m2 ) e grave (grau III; IMC ≥ 40 kg/m2 ). Dentre os fatores fisiológicos associados à obesidade, o Glucagon-like peptide-1 (GLP-1) se apresenta como um peptídeo chave, tendo como principais funções estimular a secreção de insulina dependente de glicose, reduzir o esvaziamento gástrico, melhorar a sensibilidade das células pancreáticas, inibir a liberação de glucagon e controlar a sensação de saciedade pela supressão da ingestão de alimentos e ingestão calórica. A liraglutida é um análogo do GLP-1 e apresenta homologia de 97% em relação à sequência de aminoácidos do GLP-1 huma

Cost-effectiveness analysis of using oral magnesium supplementation in the treatment of prediabetes.

INTRODUCTION: Evidence from clinical trials supports the efficacy of oral magnesium supplementation in the treatment of glucose-related disorders. Thus, we evaluate the cost-effectiveness of using oral magnesium chloride (MgCl2) in prediabetes treatment. METHODS: A cost-effectiveness analysis was performed. For such purpose, we used original information from a randomized controlled clinical trial. Analysis was carried out based on a health services provider perspective, a 10-year time horizon, and 3% discount rate for costs and effectiveness. Taking into account risk factor profiles, a Markov micro-simulation model was used, and a probabilistic sensibility analysis was performed. RESULTS: The oral MgCl2 was dominant with lower cost and greater effectiveness as compared with placebo. As compared with placebo, 22.3% and 22.0% of men using MgCl2 did not develop diabetes or cardiovascular disease. The cost per person of using MgCl2 as compared with placebo, in the individuals without complications, was $2206 versus $4048 USD for men, and $1984 versus $3272 USD for women. The sensitivity analysis confirmed the robustness of the base case. CONCLUSIONS: Our results suggest that using oral MgCl2 for at least 4 months, in adults with prediabetes and hypomagnesemia, is a cost-effective option for reducing complications and direct medical costs.

Inhibidores de dipeptidil-peptidasa 4 en pacientes con prediabetes o síndrome metabólico / Dipeptidyl-peptidase 4 inhibitors in patients with prediabetes or metabolic syndrome

CONTEXTO CLÍNICO: La Diabetes Mellitus (DM) es un desorden metabólico de etiología múltiple que se caracteriza por hiperglucemia crónica con alteraciones en la secreción y/o en la acción de la insulina. Dentro de esta entidad, la DM tipo 2 representa alrededor del 90% de las personas con DM.2 Se estima que en Argentina la prevalencia de DM tipo 2 es de un 6,2%, generando 15.545 muertes por diabetes/año en personas entre 20 y 79 años. Dentro de los factores de riesgo para el desarrollo de DM tipo 2 se encuentran el síndrome metabólico y la prediabetes.3,4 El síndrome metabólico es una entidad con diferentes definiciones (ANEXO IV), pero la mayoría de estas considera como síndrome metabólico a la presencia de dos/tres o más de los siguientes criterios: aumento de glucosa en plasma, obesidad (particularmente abdominal), hipertensión, aumento de triglicéridos y una disminución de lipoproteínas de alta densidad (HDL). La presencia de síndrome metabólico representa un aumento en el riesgo relativo para el desarrollo de DM tipo 2 de entre 3,5 y 5,1 veces. Por otra parte, la prediabetes es una fase previa al desarrollo de diabetes caracterizado por una prueba de tolerancia a la glucosa alterada y/o glucosa en ayunas alterada, y se estima que aproximadamente el 70% de las personas con prediabetes llegan a desarrollar DM tipo 2. Estas dos entidades están muy relacionadas, tanto es así que la prediabetes es uno de los criterios de síndrome metabólico, y a su vez, el aumento de triglicéridos, la disminución del HDL, y el sobrepeso son factores de riesgo para desarrollar prediabetes. TECNOLOGÍA: Los inhibidores de dipeptidil peptidasa 4 (DPP4), entre los que se encuentran: vildagliptina, saxagliptina, linagliptina, sitagliptina, tenegliptina, alogliptina, son una clase de hipoglucemiantes orales cuyo control glucémico se basa en la inhibición del DPP4, enzima que degrada incretinas como el péptido similar al glucagón 1 (GLP-1) y el polipéptido insulinotrópico dependiente de la glucosa (GIP), los cuales se liberan por el intestino durante el día y tras la ingesta. Esto lleva a un aumento de la vida media de estas enzimas y por consiguiente aumenta la liberación de insulina reduciendo los niveles de glucagón con un comportamiento dependiente del nivel de glucemia. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de inhibidores de DPP4 para pacientes con prediabetes o síndrome metabólico sin diabetes mellitus. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron cinco ECAs, una RS, cinco GPC, ocho informes de políticas de cobertura de inhibidores de DPP4 en prediabetes o enfermedades metabólicas sin diabetes mellitus. CONCLUSIONES: Evidencia de muy baja calidad no permite concluir sobre la eficacia y seguridad de los inhibidores de dipeptidil-peptidasa 4 (DPP4) en pacientes con prediabetes o síndrome metabólico sin diabetes mellitus (DM). Existen resultados promisorios sobre desenlaces importantes, como la reducción de la incidencia de DM tipo 2 o la vuelta a la normoglucemia asociado al uso de inhibidores de DPP4 combinado con metformina, en comparación a metformina sola en pacientes prediabéticos. Sin embargo, actualmente las limitaciones metodológicas de la evidencia encontrada no permiten formular una recomendación con relación al uso de los inhibidores de dipeptidil-peptidasa 4 en esta indicación. La guía de Práctica Clínica Nacional sobre Prevención, Diagnóstico y Tratamiento de la Diabetes Mellitus Tipo 2 de la Argentina, y sociedades científicas como la Asociación Estadounidense de Endocrinólogos Clínicos, Asociación Estadounidense de Diabetes y la Asociación Canadiense de Diabetes, recomiendan la metformina en caso de utilizar algún fármaco para pacientes con prediabetes y no mencionan el uso de inhibidores de DPP4 en esta población. La Asociación Latinoamericana de Diabetes establece tanto metformina como inhibidores de DPP4, entre otros fármacos, como tratamientos posibles en pacientes con prediabetes. La Administración Nacional de Medicamentos, Alimentos y Tecnología Médica de Argentina, la Administración de Medicamentos y Alimentos de los Estados Unidos y la Agencia Europea de Medicamentos, no aprobaron su uso en pacientes con prediabetes o síndrome metabólico. A su vez, diversos financiadores de salud de países de Europa y Estados Unidos cubren este fármaco en pacientes con DM tipo 2, pero no contemplan su uso en otras poblaciones, mientras que las entidades oficiales de la mayoría de los países de Latinoamérica no mencionan su cobertura para ninguna de estas indicaciones. No se encontraron estudios que evaluaran la costo-efectividad de los inhibidores de DPP4 en pacientes con prediabetes o síndrome metabólico sin diabetes mellitus. No se encontraron estudios que evaluaran la costo-efectividad de los inhibidores de DPP4 en pacientes con prediabetes o síndrome metabólico sin diabetes mellitus.

RHAPSODY, Biomarkers and Novel Clinical Trial design in type 2 diabetes (T2D) and prediabetes.

Developing a novel therapeutic product for the treatment of type 2 diabetes (T2D) is a long, resource-intensive process. Novel biomarkers could potentially aid clinical trial design by shortening clinical trials or enabling better prediction of at-risk populations and/or disease progression. Novel clinical trial designs could lead to reduced costs of development and less burden to patients, due to shorter trial duration, and/or less burdensome assessments.

Metformin Should Not Be Used to Treat Prediabetes.

Based on the results of the Diabetes Prevention Program Outcomes Study (DPPOS), in which metformin significantly decreased the development of diabetes in individuals with baseline fasting plasma glucose (FPG) concentrations of 110-125 vs. 100-109 mg/dL (6.1-6.9 vs. 5.6-6.0 mmol/L) and A1C levels 6.0-6.4% (42-46 mmol/mol) vs. <6.0% and in women with a history of gestational diabetes mellitus, it has been suggested that metformin should be used to treat people with prediabetes. Since the association between prediabetes and cardiovascular disease is due to the associated nonglycemic risk factors in people with prediabetes, not to the slightly increased glycemia, the only reason to treat with metformin is to delay or prevent the development of diabetes. There are three reasons not to do so. First, approximately two-thirds of people with prediabetes do not develop diabetes, even after many years. Second, approximately one-third of people with prediabetes return to normal glucose regulation. Third, people who meet the glycemic criteria for prediabetes are not at risk for the microvascular complications of diabetes and thus metformin treatment will not affect this important outcome. Why put people who are not at risk for the microvascular complications of diabetes on a drug (possibly for the rest of their lives) that has no immediate advantage except to lower subdiabetes glycemia to even lower levels? Rather, individuals at the highest risk for developing diabetes-i.e., those with FPG concentrations of 110-125 mg/dL (6.1-6.9 mmol/L) or A1C levels of 6.0-6.4% (42-46 mmol/mol) or women with a history of gestational diabetes mellitus-should be followed closely and metformin immediately introduced only when they are diagnosed with diabetes.

Benchmarking the Cost-Effectiveness of Interventions Delaying Diabetes: A Simulation Study Based on NAVIGATOR Data.

OBJECTIVE: To estimate using the UK Prospective Diabetes Study Outcomes Model Version 2 (UKPDS-OM2) the impact of delaying type 2 diabetes onset on costs and quality-adjusted life expectancy using trial participants who developed diabetes in the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) study. RESEARCH DESIGN AND METHODS: We simulated the impact of delaying diabetes onset by 1-9 years, utilizing data from the 3,058 of 9,306 NAVIGATOR trial participants who developed type 2 diabetes. Costs and utility weights associated with diabetes and diabetes-related complications were obtained for the U.S. and U.K. settings, with costs expressed in 2017 values. We estimated discounted lifetime costs and quality-adjusted life years (QALYs) with 95% CIs. RESULTS: Gains in QALYs increased from 0.02 (U.S. setting, 95% CI 0.01, 0.03) to 0.15 (U.S. setting, 95% CI 0.10, 0.21) as the imposed time to diabetes onset was increased from 1 to 9 years, respectively. Savings in complication costs increased from $1,388 (95% CI $1,092, $1,669) for a 1-year delay to $8,437 (95% CI $6,611, $10,197) for a delay of 9 years. Interventions costing up to $567-$2,680 and £201-£947 per year would be cost-effective at $100,000 per QALY and £20,000 per QALY thresholds in the U.S. and U.K., respectively, as the modeled delay in diabetes onset was increased from 1 to 9 years. CONCLUSIONS: Simulating a hypothetical diabetes-delaying intervention provides guidance concerning the maximum cost and minimum delay in diabetes onset needed to be cost-effective. These results can inform the ongoing debate about diabetes prevention strategies and the design of future intervention studies.

Design of a cluster-randomized trial of the effectiveness and cost-effectiveness of metformin on prevention of type 2 diabetes among prediabetic Mexican adults (the PRuDENTE initiative of Mexico City).

INTRODUCTION: Type 2 diabetes (T2D) is a global epidemic, and nations are struggling to implement effective healthcare strategies to reduce the burden. While efficacy studies demonstrate that metformin can reduce incident T2D by half among younger, obese adults with prediabetes, its real-world effectiveness are understudied, and its use for T2D prevention in primary care is low. We describe the design of a pragmatic trial to evaluate the incremental effectiveness of metformin, as an adjunct to a simple lifestyle counseling. METHODS: The "Prevención de la Diabetes con Ejercicio, Nutrición y Tratamiento" [Diabetes Prevention with Exercise, Nutrition and Treatment; PRuDENTE, (Spanish acronym)] is a cluster-randomized trial in Mexico City's public primary healthcare system. The study randomly assigns 51 clinics to deliver one of two interventions for 36 months: 1) lifestyle only; 2) lifestyle plus metformin, to 3060 patients ages 30-65 with impaired fasting glucose and obesity. The primary endpoint is incident T2D (fasting glucose ≥126 mg/dL, or HbA1c ≥6.5%). We will also measure a range of implementation-related process outcomes at the clinic-, clinician- and patient-levels to inform interpretations of effectiveness and enable efforts to refine, adapt, adopt and disseminate the model. We will also estimate the cost-effectiveness of metformin as an adjunct to lifestyle counseling in Mexico. DISCUSSION: Findings from this pragmatic trial will generate new translational knowledge in Mexico and beyond, both with respect to metformin's real-world effectiveness among an 'at-risk' population, and uncovering facilitators and barriers to the reach, adoption and implementation of metformin preventive therapy in public primary care settings. TRIAL REGISTRATION: This trial is registered at Clinicaltrials.gov (NCT03194009).

The cost-effectiveness of metformin in pre-diabetics: a systematic literature review of health economic evaluations.

Objectives: Our aim was to systematically identify and appraise cost-effectiveness studies of metformin in prediabetic subjects.Methods: A systematic literature review was conducted and reported according to standard guidlines. The search was conducted in PubMed, Embase, International Society for Pharmacoeconomics and Outcomes Research (ISPOR) presentation database and the Cost-Effectiveness Analysis (CEA) and Center for Reviews and Dissemination (CRD) registries. All cost-effectiveness studies assessing metformin in prediabetic patients were included.Results: Twenty-three reports were included. Metformin and intensive lifestyle changes (ILC) interventions were always cost-effective compared to placebo. ILC was cost-effective and sometimes dominant compared to metformin. Metformin was cost-saving compared to ILC in the short and medium-term. Although, in the long term, metformin was more expensive than ILC in terms of direct medical costs, when indirect non-medical costs are included, metformin less expensive than ILC. One study reported that for patients with Body Mass Index (BMI) higher than 30 kg/m2, metformin is a cost-effective strategy compared to placebo and ILC. However, this finding was not confirmed by other retrieved studies.Conclusion: ILC is cost-effective compared to metformin and, both of them are cost-effective compared to placebo. Metformin may be cost-saving in the short- to medium-term and possibly in the long-term.

Characteristics and Early Hypoglycemic Medications of Patients at Risk of Progression to Type 2 Diabetes in Japan: A Retrospective Cohort Study of Health Checkup and Claims Data.

Medication therapy management by tracking patients with risk of progression to type 2 diabetes has not been investigated in Japan. We aimed to assess the characteristics of these patients and their early medications. Claims (n = 190507) and health checkup data (n = 106984) between April 2005 and March 2015 in Japan were selected. We selected patients aged ≥40 years with fasting plasma glucose levels of 100-125 mg/dL or glycated hemoglobin A1c values of 5.7-6.4%. The early-medication group comprised patients who received hypoglycemic medications within 6 months after their first clinic visit, while the no-medication group comprised patients who did not receive any hypoglycemic medications. Main outcome measures were characteristics and early hypoglycemic medications of patients at risk of progression to type 2 diabetes. Of 5676 individuals, hypoglycemic medications were initiated in 276 (5%). The early-medication group had a higher proportion of individuals with a body mass index ≥25 kg/m2 and current smokers and drinkers than the no-medication group. Approximately 83% of patients in the early-medication group were prescribed a single hypoglycemic medication, and since 2010, dipeptidyl peptidase-4 inhibitors were prescribed to one-third of these patients. In our population, early hypoglycemic medication was initiated within 6 months of the first clinic visit, indicating that initiation took place earlier than recommended by current guidelines. Early hypoglycemic medications, especially dipeptidyl peptidase-4 inhibitors with low risks of hypoglycemia, might be prescribed based on patient characteristics. Further epidemiological studies are needed to confirm the suitability of early hypoglycemic medication.

[Possible to prevent prediabetes from progressing to manifest type 2 diabetes]. / Prediabetes ­ mål för intervention.

Different prediabetic states precede overt type 2 diabetes. Prediabetes also carries an increased cardiovascular risk per seand may be divided into fasting hyperglycemia, impaired glucose tolerance and intermediate hyperglycemia. Mixed forms of these are very common. Prediabetes develops insidiously for many years and usually produces no symptoms until very late. It is possible to prevent prediabetes from progressing to manifest type 2 diabetes and it can also be made to revert to normoglycemia. The importance of lifestyle interventions, pharmacological treatment, surgical treatment and community efforts is discussed.

Understanding prediabetes: definition, prevalence, burden and treatment options for an emerging disease.

Prediabetes is defined as a state of abnormal glucose homeostasis where blood glucose levels are elevated above those considered normal, but not as high as those required for a diagnosis of diabetes. As a condition intermediate between normal glucose homeostasis and the pathological condition of diabetes, the characterization of prediabetes as a distinct pathogenic condition is controversial. Emerging evidence suggests that the condition of prediabetes is associated with pathophysiological changes in several tissues and organs, which would support its recognition as a distinct pathological entity; the recent inclusion of prediabetes and associated billable conditions in the most recent ICD-10 codes provides additional credence to this position. This minireview summarizes our understanding of prediabetes and provides evidence that it should be considered a distinct and important clinical entity.

Alpha-glucosidase inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus.

BACKGROUND: Alpha-glucosidase inhibitors (AGI) reduce blood glucose levels and may thus prevent or delay type 2 diabetes mellitus (T2DM) and its associated complications in people at risk of developing of T2DM. OBJECTIVES: To assess the effects of AGI in people with impaired glucose tolerance (IGT), impaired fasting blood glucose (IFG), moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of systematic reviews, articles and health technology assessment reports. The date of the last search of all databases was December 2017. SELECTION CRITERIA: We included randomised controlled trials (RCTs), with a duration of one year or more, comparing AGI with any pharmacological glucose-lowering intervention, behaviour-changing intervention, placebo or no intervention in people with IFG, IGT, moderately elevated HbA1c or combinations of these. DATA COLLECTION AND ANALYSIS: Two review authors read all abstracts and full-text articles or records, assessed quality and extracted outcome data independently. One review author extracted data, which were checked by a second review author. We resolved discrepancies by consensus or involvement of a third review author. For meta-analyses we used a random-effects model with assessment of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the overall quality of the evidence by using the GRADE instrument. MAIN RESULTS: For this update of the Cochrane Review (first published 2006, Issue 4) we included 10 RCTs (11,814 participants), eight investigating acarbose and two investigating voglibose, that included people with IGT or people "at increased risk for diabetes". The trial duration ranged from one to six years. Most trials compared AGI with placebo (N = 4) or no intervention (N = 4).Acarbose reduced the incidence of T2DM compared to placebo: 670 out of 4014 people (16.7%) in the acarbose groups developed T2DM, compared to 812 out of 3994 people (20.3%) in the placebo groups (RR 0.82, 95% CI 0.75 to 0.89; P < 0.0001; 3 trials; 8008 participants; moderate-certainty evidence). One trial including participants with coronary heart disease and IGT contributed 64% of cases for this outcome. Acarbose reduced the risk of T2DM compared to no intervention: 7 out 75 people (9.3%) in the acarbose groups developed T2DM, compared to 18 out of 65 people (27.7%) in the no-intervention groups (RR 0.31, 95% CI 0.14 to 0.69; P = 0.004; 2 trials; 140 participants; very low-certainty evidence).Acarbose compared to placebo did not reduce or increase the risk of all-cause mortality (RR 0.98, 95% CI 0.82 to 1.18; P = 0.86; 3 trials; 8069 participants; very low-certainty evidence), cardiovascular mortality (RR 0.88; 95% CI 0.71 to 1.10; P = 0.26; 3 trials; 8069 participants; very low-certainty evidence), serious adverse events (RR 1.12, 95% CI 0.97 to 1.29; P = 0.13; 2 trials; 6625 participants; low-certainty evidence), non-fatal stroke (RR 0.50, 95% CI 0.09 to 2.74; P = 0.43; 1 trial; 1368 participants; very low-certainty evidence) or congestive heart failure (RR of 0.87; 95% CI 0.63 to 1.12; P = 0.40; 2 trials; 7890 participants; low-certainty evidence). Acarbose compared to placebo reduced non-fatal myocardial infarction: one out of 742 participants (0.1%) in the acarbose groups had a non-fatal myocardial infarction compared to 15 out of 744 participants (2%) in the placebo groups (RR 0.10, 95% CI 0.02 to 0.53; P = 0.007; 2 trials; 1486 participants; very low-certainty evidence). Acarbose treatment showed an increased risk of non-serious adverse events (mainly gastro-intestinal events), compared to placebo: 751 of 775 people (96.9%) in the acarbose groups experienced an event, compared to 723 of 775 people (93.3%) in the placebo groups (RR 1.04; 95% CI 1.01 to 1.06; P = 0.0008; 2 trials; 1550 participants). Acarbose compared to no intervention showed no advantage or disadvantage for any of these outcome measures (very low-certainty evidence).One trial each compared voglibose with placebo (1780 participants) or diet and exercise (870 participants). Voglibose compared to placebo reduced the incidence of T2DM: 50 out of 897 participants (5.6%) developed T2DM, compared to 106 out of 881 participants (12%) in the placebo group (RR 0.46, 95% CI 0.34 to 0.64; P < 0.0001; 1 trial; 1778 participants; low-certainty evidence). For all other reported outcome measures there were no clear differences between voglibose and comparator groups. One trial with 90 participants compared acarbose with diet and exercise and another trial with 98 participants reported data on acarbose versus metformin. There were no clear differences for any outcome measure between these two acarbose interventions and the associated comparator groups.None of the trials reported amputation of lower extremity, blindness or severe vision loss, end-stage renal disease, health-related quality of life, time to progression to T2DM, or socioeconomic effects. AUTHORS' CONCLUSIONS: AGI may prevent or delay the development of T2DM in people with IGT. There is no firm evidence that AGI have a beneficial effect on cardiovascular mortality or cardiovascular events.

Review of Metformin Use for Type 2 Diabetes Prevention.

CONTEXT: Prediabetes is prevalent and significantly increases lifetime risk of progression to type 2 diabetes. This review summarizes the evidence surrounding metformin use for type 2 diabetes prevention. EVIDENCE ACQUISITION: Articles published between 1998 and 2017 examining metformin use for the primary indication of diabetes prevention available on MEDLINE. EVIDENCE SYNTHESIS: Forty articles met inclusion criteria and were summarized into four general categories: (1) RCTs of metformin use for diabetes prevention (n=7 and n=2 follow-up analyses); (2) observational analyses examining metformin use in heterogeneous subgroups of patients with prediabetes (n=9 from the Diabetes Prevention Program, n=1 from the biguanides and the prevention of the risk of obesity [BIGPRO] trial); (3) observational analyses examining cost effectiveness of metformin use for diabetes prevention (n=11 from the Diabetes Prevention Program, n=1 from the Indian Diabetes Prevention Program); and (4) real-world assessments of metformin eligibility or use for diabetes prevention (n=9). Metformin was associated with reduced relative risk of incident diabetes, with the strongest evidence for use in those at highest risk (i.e., aged <60 years, BMI ≥35, and women with histories of gestational diabetes). Metformin was also deemed cost effective in 11 economic analyses. Recent studies highlighted low rates of metformin use for diabetes prevention in real-world settings. CONCLUSIONS: Two decades of evidence support metformin use for diabetes prevention among higher-risk patients. However, metformin is not widely used in real-world practice, and enhancing the translation of this evidence to real-world practice has important implications for patients, providers, and payers.

Preventing type 2 diabetes: systematic review of studies of cost-effectiveness of lifestyle programmes and metformin, with and without screening, for pre-diabetes.

OBJECTIVE: Explore the cost-effectiveness of lifestyle interventions and metformin in reducing subsequent incidence of type 2 diabetes, both alone and in combination with a screening programme to identify high-risk individuals. DESIGN: Systematic review of economic evaluations. DATA SOURCES AND ELIGIBILITY CRITERIA: Database searches (Embase, Medline, PreMedline, NHS EED) and citation tracking identified economic evaluations of lifestyle interventions or metformin alone or in combination with screening programmes in people at high risk of developing diabetes. The International Society for Pharmaco-economics and Outcomes Research's Questionnaire to Assess Relevance and Credibility of Modelling Studies for Informing Healthcare Decision Making was used to assess study quality. RESULTS: 27 studies were included; all had evaluated lifestyle interventions and 12 also evaluated metformin. Primary studies exhibited considerable heterogeneity in definitions of pre-diabetes and intensity and duration of lifestyle programmes. Lifestyle programmes and metformin appeared to be cost effective in preventing diabetes in high-risk individuals (median incremental cost-effectiveness ratios of £7490/quality-adjusted life-year (QALY) and £8428/QALY, respectively) but economic estimates varied widely between studies. Intervention-only programmes were in general more cost effective than programmes that also included a screening component. The longer the period evaluated, the more cost-effective interventions appeared. In the few studies that evaluated other economic considerations, budget impact of prevention programmes was moderate (0.13%-0.2% of total healthcare budget), financial payoffs were delayed (by 9-14 years) and impact on incident cases of diabetes was limited (0.1%-1.6% reduction). There was insufficient evidence to answer the question of (1) whether lifestyle programmes are more cost effective than metformin or (2) whether low-intensity lifestyle interventions are more cost effective than the more intensive lifestyle programmes that were tested in trials. CONCLUSIONS: The economics of preventing diabetes are complex. There is some evidence that diabetes prevention programmes are cost effective, but the evidence base to date provides few clear answers regarding design of prevention programmes because of differences in denominator populations, definitions, interventions and modelling assumptions.

Assessment of the Therapeutic Potential of Persimmon Leaf Extract on Prediabetic Subjects.

Dietary supplements have exhibited myriads of positive health effects on human health conditions and with the advent of new technological advances, including in the fields of proteomics, genomics, and metabolomics, biological and pharmacological activities of dietary supplements are being evaluated for their ameliorative effects in human ailments. Recent interests in understanding and discovering the molecular targets of phytochemical-gene-protein-metabolite dynamics resulted in discovery of a few protein signature candidates that could potentially be used to assess the effects of dietary supplements on human health. Persimmon (Diospyros kaki) is a folk medicine, commonly used as dietary supplement in China, Japan, and South Korea, owing to its different beneficial health effects including anti-diabetic implications. However, neither mechanism of action nor molecular biomarkers have been discovered that could either validate or be used to evaluate effects of persimmon on human health. In present study, Mass Spectrometry (MS)-based proteomic studies were accomplished to discover proteomic molecular signatures that could be used to understand therapeutic potentials of persimmon leaf extract (PLE) in diabetes amelioration. Saliva, serum, and urine samples were analyzed and we propose that salivary proteins can be used for evaluating treatment effectiveness and in improving patient compliance. The present discovery proteomics study demonstrates that salivary proteomic profile changes were found as a result of PLE treatment in prediabetic subjects that could specifically be used as potential protein signature candidates.

Identification and management of prediabetes: results of the Latin America Strategic Prediabetes Meeting / Identificación y manejo de la prediabetes: resultados del Encuentro Estratégico de Prediabetes de América Latina / Identificação e gerenciamento de prediabetes: resultados da Reunião Estratégica de Prediabetes da América Latina

ABSTRACT To understand the status of prediabetes diagnosis and treatment in Latin America and to evaluate the use of metformin for diabetes prevention in this context. A panel of 15 diabetes experts from seven countries in Latin America met on 14 - 15 August 2014 in Lima, Peru, to review the available literature, discuss the role of prediabetes in type 2 diabetes mellitus and cardiovascular disease, analyze collected information, and make conclusions for prediabetes diagnosis and treatment in Latin America. Prediabetes diagnosis, screening, and treatment, including lifestyle changes, pharmacological treatment, and cost-effectiveness were discussed. Five resulting statements were issued for Latin America: prediabetes is a clinical and public health problem; health care systems do not currently diagnose/treat prediabetes; use of prediabetes risk detection tools are needed region-wide; treatment includes lifestyle changes, multidisciplinary education, and metformin; and registries of patient records and further studies should be supported. The expert panel concluded that in Latin America, preventive treatment through lifestyle changes and metformin are cost-effective interventions. It is important to improve prediabetes identification and management at the primary care level.(AU)

RESUMEN Comprender el estado del diagnóstico y el tratamiento de la prediabetes en América Latina y evaluar el uso de la metformina para la prevención de la diabetes en este contexto. Un panel de 15 expertos en diabetes de siete países de América Latina se reunió del 14 al 15 de agosto de 2014 en Lima, Perú, para revisar la literatura disponible, discutir el papel de la prediabetes en la diabetes mellitus tipo 2 y la enfermedad cardiovascular, analizar la información recolectada y formular conclusiones para el diagnóstico y el tratamiento de la prediabetes en América Latina. Se analizaron el diagnóstico, el tamizaje y el tratamiento de la prediabetes, inclusive los cambios en el estilo de vida, el tratamiento farmacológico y la relación costo-eficacia. Se emitieron cinco conclusiones para América Latina: la prediabetes es un problema clínico y de salud pública; los sistemas de atención de la salud actualmente no diagnostican o no tratan la prediabetes; el uso de herramientas de detección del riesgo de prediabetes es necesario en toda la región; el tratamiento incluye cambios en el estilo de vida, educación multidisciplinaria y metformina; y se debe brindar apoyo para llevar registros de historias clínicas y realizar estudios adicionales. El panel de expertos concluyó que en América Latina el tratamiento preventivo basado en cambios en el estilo de vida y administración de metformina son intervenciones eficaces en relación al costo. Es importante mejorar la identificación y el manejo de la prediabetes en el nivel de atención primaria.(AU)

RESUMO Entender o estado do diagnóstico e tratamento do prediabetes na América Latina e avaliar o uso de metformina para prevenção de diabetes neste contexto. Um painel de 15 especialistas em diabetes de sete países da América Latina reuniu-se de 14 a 15 de agosto de 2014 em Lima, Peru, para analisar a literatura disponível, discutir o papel do prediabetes em diabetes mellitus tipo 2 e doenças cardiovasculares, analisar informações coletadas e fazer conclusões para o diagnóstico e tratamento do prediabetes na América Latina. O diagnóstico, rastreio e tratamento pré-diabetes, incluindo mudanças de estilo de vida, tratamento farmacológico e custo-efetividade foram discutidos. Foram emitidas cinco conclusões resultantes para a América Latina: o prediabetes é um problema clínico e de saúde pública; os sistemas de saúde atualmente não diagnosticam/tratam prediabetes; o uso de ferramentas de detecção de risco de prediabetes é necessário em toda a região; o tratamento inclui mudanças de estilo de vida, educação multidisciplinar e metformina; e devem ser suportados registros de pacientes e outros estudos. O painel de especialistas concluiu que na América Latina, o tratamento preventivo através de mudanças de estilo de vida e metformina são intervenções efetivas em relação ao custo. É importante melhorar a identificação e gestão do prediabetes no nível de atenção primária.(AU)

Assessment of the effeCt of lIfestyle iNtervention plus water-soluble ciNnAMon extract On loweriNg blood glucose in pre-diabetics, a randomized, double-blind, multicenter, placebo controlled trial: study protocol for a randomized controlled trial.

BACKGROUND: The World Health Organization predicts that by 2030 diabetes will be the seventh leading cause of death in the world. Multiple studies have tried to determine if cinnamon is an effective treatment for diabetes. Cinnamon extract is an insulin sensitizer, protects mesangial cells, decreases inflammatory markers, and lowers glucose, lipids, and blood pressure in patients with type 2 diabetes, so we developed a protocol to study whether ingestion of water-soluble cinnamon extract prevents progression from pre-diabetes to diabetes. METHODS/DESIGN: This is a randomized, double-blind, placebo-controlled trial comparing cinnamon extract versus placebo in subjects with pre-diabetes who have committed to participate in a lifestyle change program. The trial will be conducted at five sites and will include 428 subjects who take cinnamon extract or placebo for 1 year. Follow-up for these subjects will be for a total of 2 years (nine study visits). The primary outcomes to be assessed are 1) conversion of patients from pre-diabetes to diabetes and 2) impact of water-soluble cinnamon extract on hepatic transaminases, renal function, and QT interval on electrocardiogram. Secondary outcomes include changes in HbA1c, lipids, waist circumference, weight, blood pressure, and fasting plasma glucose. The trial protocol has been approved by the Institutional Review Board of the US Air Force 59th Medical Wing, Wilford Hall Ambulatory Surgical Center (Protocol FWH20110035H). Investigator-sponsored Investigational New Drug status (114078) was granted by the US Food and Drug Administration. DISCUSSION: This study will provide high-quality evidence of the efficacy of water-soluble cinnamon extract in conjunction with lifestyle intervention for preventing patients with pre-diabetes from converting to diabetes. Additionally, it will provide important safety information about water-soluble cinnamon extract. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01301521 , 18 February 2011.

The rationale, design, and baseline characteristics of PREVENT-DM: A community-based comparative effectiveness trial of lifestyle intervention and metformin among Latinas with prediabetes.

Promotora Effectiveness Versus Metformin Trial (PREVENT-DM) is a randomized comparative effectiveness trial of a lifestyle intervention based on the Diabetes Prevention Program delivered by community health workers (or promotoras), metformin, and standard care. Eligibility criteria are Hispanic ethnicity, female sex, age ≥ 20 years, fluent Spanish-speaking status, BMI ≥ 23 kg/m(2), and prediabetes. We enrolled 92 participants and randomized them to one of the following three groups: standard care, DPP-based lifestyle intervention, or metformin. The primary outcome of the trial is the 12-month difference in weight between groups. Secondary outcomes include the following cardiometabolic markers: BMI, waist circumference, blood pressure, and fasting plasma glucose, hemoglobin A1C (HbA1c), total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, and insulin. PREVENT-DM participants are socioeconomically disadvantaged Latinas with a mean annual household income of $15,527 ± 9922 and educational attainment of 9.7 ± 3.6 years. Eighty-six percent of participants are foreign born, 20% have a prior history of gestational diabetes, and 71% have a first-degree relative with diagnosed diabetes. At baseline, PREVENT-DM participants had a mean age of 45.1 ± 12.5 years, weight of 178.8 ± 39.3 lbs, BMI of 33.3 ± 6.5 kg/m(2), HbA1c of 5.9 ± 0.2%, and waist circumference of 97.4 ± 11.1cm. Mean baseline levels of other cardiometabolic markers were normal. The PREVENT-DM study successfully recruited and randomized an understudied population of Latinas with prediabetes. This trial will be the first U.S. study to test the comparative effectiveness of metformin and lifestyle intervention versus standard care among prediabetic adults in a "real-world" setting.

The cost-effectiveness analysis of JinQi Jiangtang tablets for the treatment on prediabetes: a randomized, double-blind, placebo-controlled, multicenter design.

BACKGROUND: At present, diabetes is a chronic disease of great cost and heavy burdens. The International Diabetes Federation has repeatedly warned that by 2025, the global number of diabetics would rise to 333 million from 194 million in 2003. Although the occurrence of diabetes in developing countries is lower, China has a large population, so that the number of cases is increased. At the same time, more people have prediabetes, a growing health concern where a large percentage of the patients develop full type 2 diabetes. In addition, the patients of diabetes easily incur complications such as blindness, kidney failure, and cardiovascular diseases that can seriously affect the patients' quality of life and cause great economic burdens to family and society. Therefore, effective interventions for prediabetes are needed to prevent or delay the occurrence and development of diabetes. METHODS: A randomized controlled trial that was assessed with pharmacoeconomic methods was undertaken in this study. The study term was 24 months (12 months for the intervention and 12 months for follow up). Four hundred participants, recruited from four cities in China: Beijing, Tianjin, Xian, and Naning, were randomized to the treatment group (JQJT tablets) and the control group (placebo). Participants included in this study had been diagnosed with prediabetes according to the criteria for western medicine and Traditional Chinese Medicine (TCM). The end-point effectiveness indexes included the incidence of diabetes and the reversion rate. The drug costs and lifestyle intervention costs were included in the total costs. The study used the cost-effectiveness analysis to discuss the economic advantage of the JQJT tablets. RESULTS: The outcomes of the study contained 2 sections,namely clinical outcomes and cost-effectiveness analysis outcomes. The clinical outcomes: the treatment group and control group had no significant statistical difference P> 0.05) on the baseline of situation; Jinqi Jiangtang tablet effectively reduced the incidence of diabetes mellitus and enhanced reversion rate. compared with the control group (p< 0.05); the scores of SF-36 of two groups had no significant difference P> 0.05); finally the compliance of participants between the two groups had no significant difference. The cost-effectiveness analysis outcomes:in the intervention period of 12 months,on the aspect of reversion rate, the treatment group had better economic advantage by using cost-effectiveness ratio and the incremental cost-effectiveness ratio;on the aspect of the incidence of diabetes, the control group had better economic advantage by using cost-effectiveness ratio and the incremental cost-effectiveness ratio; in the follow-up period of 24 months, on the aspect of reversion rate, the treatment group had better economic advantage by using cost-effectiveness ratio and the incremental cost-effectiveness ratio, on the aspect of the incidence of diabetes, the control group had better economic advantage by using cost-effectivenes ratio and the incremental cost-effectiveness ratio.At the same time, these outcomes remained the same by sensitivity analysis. Assuming that prices and resident incomes rose 5%, the sensitiveness analysis shows that the two group affected by the paremeters changed little. CONCLUSION: The importance and effectiveness of lifestyle education and JinQi Jiangtang tablets was proven. In both the intervention period and follow-up, JinQi Jiangtang tablets combined with lifestyle education had a greater cost advantage effect than the lifestyle education alone on the reversion rate; the lifestyle education had a greater cost advantage effect than the JinQi Jiangtang tablets combined with lifestyle education on the incidence of diabetes. TRIAL REGISTRATION: Chinese Clinical Trials ChiCTR-TRC-09000401 ) , registered on 25 May 2009.