RESUMO
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 ß-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 ß-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.
Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/administração & dosagem , Vildagliptina/administração & dosagem , Adolescente , Adulto , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Humanos , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/fisiologia , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Fatores de Tempo , Vildagliptina/efeitos adversos , Adulto JovemRESUMO
BACKGROUND AND AIMS: Screening for Gestational Diabetes (GDM) is usually recommended between 24 and 28 weeks of pregnancy; however available evidence suggests that GDM may be already present before recommended time for screening, in particular among high-risk women as those with prior GDM or obesity. The purpose of this retrospective study was to evaluate whether early screening (16-18 weeks) and treatment of GDM may improve maternal and fetal outcomes. METHODS AND RESULTS: In 290 women at high-risk for GDM, we analyzed maternal and fetal outcomes, according to early or standard screening and GDM diagnosis time. Early screening was performed by 50% of high-risk women. The prevalence of GDM was 62%. Among those who underwent early screened, GDM was diagnosed at the first evaluation in 42.7%. Women with early diagnosis were more frequently treated with insulin and had a slightly lower HbA1c than women with who were diagnosed late. No differences were observed in the prevalence of Cesarean section, operative delivery, gestational age at the delivery, macrosomia, neonatal weight, Ponderal Index and Large-for-Gestational-Age among women with early or late GDM diagnosis or NGT. However, compared to NGT women, GDM women, irrespective of the time of diagnosis, had a lower gestational weight gain, lower prevalence of macrosomia (3.9% vs. 11.4%), small (1.7% vs. 8.3%) as well as large for gestational age (3.3% vs. 16.7%), but higher prevalence of pre-term delivery (8.9% vs. 2.7%). CONCLUSION: Early vs. standard screening and treatment of GDM in high-risk women is associated with similar short-term maternal-fetal outcomes, although women with an early diagnosis were treated to a greater extent with insulin therapy.
Assuntos
Diabetes Gestacional/diagnóstico , Diabetes Gestacional/tratamento farmacológico , Intervenção Médica Precoce , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Programas de Rastreamento , Cuidado Pré-Natal/métodos , Adulto , Diabetes Gestacional/sangue , Diabetes Gestacional/epidemiologia , Diagnóstico Precoce , Feminino , Humanos , Itália/epidemiologia , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Until recently, in Italy, the use of continuous glucose monitoring (CGM) systems has been limited, but is now rapidly increasing, including the so-called real-time CGM (rtCGM) and the intermittently viewed CGM (iCGM), also called Flash Glucose Monitoring (FGM). These technologies overcome many of the limitations of self-monitoring of blood glucose (SMBG) by fingerprick and allow to go beyond HbA1c to check glucose control in diabetes. However, standardized protocols for applying and interpreting rtCGM and FGM data are lacking. In this paper, we delineate a consensus amongst Italian diabetes physicians on the attributes of rtCGM and FGM technologies, and introduce a consistent approach for their use by Italian healthcare professionals. Most experts consider rtCGM and FGM as two separate categories of interstitial subcutaneous fluid (ISF) sensing technologies, and see them as superior to SMBG. Furthermore, there is strong consensus that rtCGM and FGM reduce hypoglycemia risk, increase the amount of time in the target glucose range and augment treatment satisfaction. However, there is still no agreement on the indication of the FGM for subjects who suffer asymptomatic hypoglycemia. Consensus on the role of education in initiating and optimizing use of rtCGM/FGM and about the interpretation of glucose trends was near unanimous, whereas no consensus was reached on the statement that there are no disadvantages/risks of rtCGM/FGM. Some issues remain in rtCGM/FGM management: a) risk of excessive correction of high or low glucose; b) risk of alert fatigue leading to alert silencing or rtCGM termination; c) allergic reaction to the adhesive keeping rtCGM or FGM sensors in place. The panel almost unanimously agreed that sensor accuracy depends on multiple variables, that alarm setting should be individualized, and that global glycemic profile represent an useful tool in interpreting glucose data. More clinical studies and a wider use of these devices will increase the efficacy and effectiveness of continuous glucose monitoring in Italy.
Assuntos
Técnicas Biossensoriais/instrumentação , Automonitorização da Glicemia/instrumentação , Glicemia/metabolismo , Diabetes Mellitus/diagnóstico , Líquido Extracelular/metabolismo , Dispositivos Eletrônicos Vestíveis , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Consenso , Técnica Delphi , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Desenho de Equipamento , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Itália , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do TratamentoRESUMO
Gestational diabetes mellitus (GDM) is a complex condition whose physiopathology to date has not been completely clarified. Two major metabolic disorders, insulin resistance and ß-cells dysfunction, play currently major role in pathogenesis of GDM. These elements are influenced by the amount of adipose tissue present before and/or during the pregnancy. Consequently, adipokines (adiponectin (APN), leptin (LPT), adipocyte fatty acid-binding protein, resistin, visfatin, omentin, vaspin, apelin, chemerin) secreted by adipose tissue, may contribute directly and/or indirectly, through the enhancement of chronic inflammation, aggravating insulin resistance and promoting GDM onset. This review aims to outline the potential physiopathological and prognostic role in GDM of adipokines, mainly APN and LPT.
Assuntos
Adipocinas/fisiologia , Diabetes Gestacional/etiologia , Tecido Adiposo/metabolismo , Animais , Diabetes Gestacional/metabolismo , Feminino , Humanos , Resistência à Insulina/fisiologia , GravidezRESUMO
BACKGROUND AND AIM: In 2011, the Italian National Health System guidelines introduced a selective screening for gestational diabetes (GDM) based on risk factors, recommending early evaluation in high risk women. The present study examined to which extent guidelines are applied, and analyzed the effectiveness of GDM diagnosis according to risk profile. METHODS AND RESULTS: We analyzed 1338 pregnant women, consecutively screened for GDM with a 75 g OGTT between January 2013 and December 2015, according to national guidelines. Diagnosis of GDM was based on IADPSG/WHO 2013 criteria. As many as 14.4% of screened women was at high risk, 64% at medium, 21.6% did not have any risk factor. Only 50% of high-risk women were appropriately screened at 16th-18th gestational weeks; 28% of them repeated the OGTT due to NGT. The overall prevalence of GDM was 39.9%, higher in high risk women (67% vs. 40% medium risk vs. 22% low risk; p < 0.0001). An early GDM diagnosis was performed in 40.7% of high-risk women. In low risk women, gestational weight gain at the screening time was independently associated with GDM. CONCLUSIONS: The recommendations for the screening of GDM are still insufficiently implemented, especially for early evaluation in high risk women. Considering the high proportion of early GDM diagnosis, the poor adherence to screening recommendation may result in late diagnosis of GDM. Finally, our finding of a 22% prevalence of GDM among low risk women suggests the need to consider additional risk factors, such as excessive weight gain during pregnancy.
Assuntos
Diabetes Gestacional/diagnóstico , Fidelidade a Diretrizes/normas , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Cuidado Pré-Natal/normas , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/fisiopatologia , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Itália/epidemiologia , Fenômenos Fisiológicos da Nutrição Materna , Estado Nutricional , Valor Preditivo dos Testes , Gravidez , Prevalência , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Aumento de PesoRESUMO
This was a post hoc analysis of a 2-year, double-blind study of 2639 patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin monotherapy, which assessed achievement of a composite endpoint of sustained glycated haemoglobin (HbA1c) reduction (≤7.0% at week 104 or ≥0.5% decrease from baseline) with no weight gain and no hypoglycaemic events with alogliptin 12.5 and 25 mg daily or glipizide (≤20 mg daily), each added to metformin. With an HbA1c target of ≤7.0%, 24.2 and 26.9% of patients treated with alogliptin 12.5 and 25 mg, respectively, achieved the composite endpoint versus 10.7% of patients treated with glipizide (both p < 0.001). With a criterion of ≥0.5% decrease in HbA1c, the composite endpoint was reached in 22.5, 25.2 and 10.4% of patients treated with alogliptin 12.5 mg, alogliptin 25 mg and glipizide, respectively. Odds ratios for achieving the composite endpoint favoured alogliptin in the primary analysis set and in all subgroups of patients. Patients with T2DM failing metformin monotherapy were more likely to achieve sustained glycaemic control with no hypoglycaemia or weight gain at 2 years with alogliptin than with glipizide.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Glipizida/administração & dosagem , Hemoglobinas Glicadas/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Piperidinas/administração & dosagem , Uracila/análogos & derivados , Aumento de Peso/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Determinação de Ponto Final , Feminino , Glipizida/efeitos adversos , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/administração & dosagem , Metformina/efeitos adversos , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Resultado do Tratamento , Uracila/administração & dosagem , Uracila/efeitos adversos , Adulto JovemRESUMO
This substudy of the AWARD-3 trial evaluated the effects of the once-weekly glucagon-like peptide-1 receptor agonist, dulaglutide, versus metformin on glucose control, pancreatic function and insulin sensitivity, after standardized test meals in patients with type 2 diabetes. Meals were administered at baseline, 26 and 52 weeks to patients randomized to monotherapy with dulaglutide 1.5 mg/week (n = 133), dulaglutide 0.75 mg/week (n = 136), or metformin ≥1500 mg/day (n = 140). Fasting and postprandial serum glucose, insulin, C-peptide and glucagon levels were measured up to 3 h post-meal. ß-cell function and insulin sensitivity were assessed using empirical variables and mathematical modelling. At 26 weeks, similar decreases in area under the curve for glucose [AUCglucose (0-3 h)] were observed among all groups. ß-cell function [AUCinsulin /AUCglucose (0-3 h)] increased with dulaglutide and was unchanged with metformin (p ≤ 0.005, both doses). Dulaglutide improved insulin secretion rate at 9 mmol/l glucose (p ≤ 0.04, both doses) and ß-cell glucose sensitivity (p = 0.004, dulaglutide 1.5 mg). Insulin sensitivity increased more with metformin versus dulaglutide. In conclusion, dulaglutide improves postprandial glycaemic control after a standardized test meal by enhancing ß-cell function, while metformin exerts a greater effect on insulin sensitivity.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hipoglicemiantes/uso terapêutico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Resistência à Insulina , Metformina/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Adulto , Idoso , Área Sob a Curva , Glicemia/metabolismo , Peptídeo C/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Jejum , Feminino , Glucagon/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Resultado do TratamentoRESUMO
PURPOSE: The optimal macronutrient composition of the diet for the management of type 2 diabetes is debated, particularly with regard to the ideal proportion of fat and carbohydrates. The aim of the study was to explore the association of different proportions of fat and carbohydrates of the diet-within the ranges recommended by different guidelines-with metabolic risk factors. METHODS: We studied 1785 people with type 2 diabetes, aged 50-75, enrolled in the TOSCA.IT Study. Dietary habits were assessed using a validated food-frequency questionnaire (EPIC). Anthropometry, fasting lipids, HbA1c and C-reactive protein (CRP) were measured. RESULTS: Increasing fat intake from <25 to ≥35 % is associated with a significant increase in LDL-cholesterol, triglycerides, HbA1c and CRP (p < 0.05). Increasing carbohydrates intake from <45 to ≥60 % is associated with significantly lower triglycerides, HbA1c and CRP (p < 0.05). A fiber intake ≥15 g/1000 kcal is associated with a better plasma lipids profile and lower HbA1c and CRP than lower fiber consumption. A consumption of added sugars of ≥10 % of the energy intake is associated with a more adverse plasma lipids profile and higher CRP than lower intake. CONCLUSIONS: In people with type 2 diabetes, variations in the proportion of fat and carbohydrates of the diet, within the relatively narrow ranges recommended by different nutritional guidelines, significantly impact on the metabolic profile and markers of low-grade inflammation. The data support the potential for reducing the intake of fat and added sugars, preferring complex, slowly absorbable, carbohydrates.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Inflamação/sangue , Idoso , Proteína C-Reativa/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Fibras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Ingestão de Energia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Triglicerídeos/sangueRESUMO
BACKGROUND AND AIMS: We aimed to determine if patient baseline characteristics affect responses to linagliptin and identify relevant predictors of glycated hemoglobin (HbA1c) reduction in patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Data were pooled from three 24-week, placebo-controlled trials of similar design (linagliptin, n = 1651; placebo, n = 607). Patients were categorized according to baseline characteristics: age, T2DM duration, gender, body mass index (BMI), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and metabolic syndrome (MetS). Changes from baseline in HbA1c after 24 weeks were assessed with analysis of covariance (ANCOVA). The proportion of patients with baseline HbA1c >7% achieving HbA1c of ≤7% at week 24 were evaluated. Independent predictors of HbA1c response with linagliptin were analyzed in a multivariate analysis with ANCOVA. Linagliptin treatment led to significant mean (SE) placebo-corrected reductions from baseline in HbA1c across all subgroups (-0.42% [±0.11] to -0.79% [0.08]; all p < 0.001). Within subgroups, HbA1c reduction was more pronounced in patients without MetS (-0.74% [0.06]; treatment interaction p = 0.0489). The proportion of patients with baseline HbA1c >7% achieving a target HbA1c ≤7% was greater with linagliptin versus placebo (30.2% vs 11.5%; odds ratio 3.82; 95% CI 2.82 to 5.17; p < 0.001). Characteristics significantly predicting HbA1c reductions after 24 weeks were fasting plasma glucose and race (both p < 0.05). CONCLUSION: This post-hoc analysis supports that linagliptin achieved clinically meaningful improvements in hyperglycemia in patients with diverse clinical characteristics. These improvements were more pronounced in patients without MetS.
Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Linagliptina/uso terapêutico , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Ensaios Clínicos Fase III como Assunto , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Linagliptina/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
AIMS: Type 2 diabetes mellitus (T2DM) is associated with a high risk of chronic kidney disease (CKD). About 20% of patients with T2DM have CKD of stage ≥ 3; up to 40% have some degree of CKD. Beyond targeting all renal risk factors together, renin-angiotensin-aldosterone system blockers are to date the only effective mainstay for the treatment of diabetic kidney disease (DKD). Indeed, several potentially nephroprotective agents have been in use, which have been unsuccessful. Some glucose-lowering agents, including dipeptidyl peptidase-4 inhibitors (DPP-4i), have shown promising results. Here, we discuss the evidence that glucose lowering with DPP-4i may be an option for protecting against diabetes-related renal injury. DATA SYNTHESIS: A comprehensive search was performed of the literature using the terms "alogliptin," "linagliptin," "saxagliptin," "sitagliptin," and "vildagliptin" for original articles and reviews addressing this topic. DPP-4i are an effective, well-tolerated treatment option for T2DM with any degree of renal impairment. Preclinical observations and clinical studies suggest that DPP-4i might also be a promising strategy for the treatment of DKD. The available data are in favor of saxagliptin and linagliptin, but the consistency of results points to the possible nephroprotective effect of DPP-4i. This property appears to be independent of glucose lowering and can potentially complement other therapies that preserve renal function. Larger prospective clinical trials are ongoing, which might strengthen these hypothesis-generating findings. CONCLUSIONS: The improvement in albuminuria associated with DPP-4i suggests that these agents may provide renal benefits beyond their glucose-lowering effects, thus offering direct protection from DKD. These promising results must be interpreted with caution and need to be confirmed in forthcoming studies.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Rim/efeitos dos fármacos , Insuficiência Renal Crônica/prevenção & controle , Albuminúria/enzimologia , Albuminúria/etiologia , Albuminúria/prevenção & controle , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/enzimologia , Nefropatias Diabéticas/enzimologia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Rim/enzimologia , Rim/fisiopatologia , Insuficiência Renal Crônica/enzimologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Resultado do TratamentoRESUMO
The prevalence of type 2 diabetes mellitus (T2DM) among elderly people is increasing. Often associated with disabilities/comorbidities, T2DM lowers the chances of successful aging and is independently associated with frailty and an increased risk of hypoglycaemia, which can be further exacerbated by antihyperglycaemic treatment. From this perspective, the clinical management of T2DM in the elderly is challenging and requires individualization of optimum glycaemic targets depending on comorbidities, cognitive functioning and ability to recognize and self-manage the disease. The lack of solid evidence-based medicine supporting treatment guidelines for older people with diabetes further complicates the matter. Several classes of medicine for the treatment of T2DM are currently available and different drug combinations are often required to achieve individualized glycaemic goals. Many of these drugs, however, carry disadvantages such as the propensity to cause weight gain or hypoglycaemia. Dipeptidyl peptidase-4 (DPP-4) inhibitors, a recent addition to the pharmacological armamentarium, have become widely accepted in clinical practice because of their efficacy, low risk of hypoglycaemia, neutral effect on body weight, and apparently greater safety in patients with kidney failure. Although more information is needed to reach definitive conclusions, growing evidence suggests that DPP-4 inhibitors may become a valuable component in the pharmacological management of elderly people with T2DM. The present review aims to delineate the potential advantages of this pharmacological approach in the treatment of elderly people with T2DM.
Assuntos
Adamantano/análogos & derivados , Glicemia/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemia/prevenção & controle , Nitrilas/uso terapêutico , Pirrolidinas/uso terapêutico , Adamantano/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Peso Corporal/efeitos dos fármacos , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/sangue , Medicina Baseada em Evidências , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , Hipoglicemia/induzido quimicamente , Guias de Prática Clínica como Assunto , Qualidade de Vida , VildagliptinaRESUMO
AIMS: To report the cardiovascular (CV) safety profile and heart failure (HF) risk of vildagliptin from a large pool of studies, including trials in high-risk patients with type 2 diabetes mellitus (T2DM), such as those with congestive HF and/or moderate/severe renal impairment. METHODS: We conducted a retrospective meta-analysis of prospectively adjudicated CV events. Patient-level data were pooled from 40 double-blind, randomized controlled phase III and IV vildagliptin studies. The primary endpoint was occurrence of major adverse CV events (MACEs; myocardial infarction, stroke and CV death). Assessments of the individual MACE components and HF events (requiring hospitalization or new onset) were secondary endpoints. The risk ratio (RR) of vildagliptin (50 mg once- and twice-daily combined) versus comparators (placebo and all non-vildagliptin treatments) was calculated using the Mantel-Haenszel (M-H) method. RESULTS: Of the 17 446 patients, 9599 received vildagliptin (9251.4 subject-years of exposure) and 7847 received comparators (7317.0 subject-years of exposure). The mean age of the patients was 57 years, body mass index 30.5 kg/m(2) (nearly 50% obese), glycated haemoglobin concentration 8.1% and T2DM duration 5.5 years. A MACE occurred in 83 (0.86%) vildagliptin-treated patients and 85 (1.20%) comparator-treated patients, with an M-H RR of 0.82 [95% confidence interval (CI) 0.61-1.11]. Similar RRs were observed for the individual events. Confirmed HF events were reported in 41 (0.43%) vildagliptin-treated patients and 32 (0.45%) comparator-treated patients, with an M-H RR 1.08 (95% CI 0.68-1.70). CONCLUSIONS: This large meta-analysis indicates that vildagliptin is not associated with an increased risk of adjudicated MACEs relative to comparators. Moreover, this analysis did not find a significant increased risk of HF in vildagliptin-treated patients.
Assuntos
Adamantano/análogos & derivados , Doenças Cardiovasculares/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Nitrilas/efeitos adversos , Pirrolidinas/efeitos adversos , Adamantano/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , VildagliptinaRESUMO
AIMS: To assess the long-term efficacy and tolerability of dapagliflozin versus glipizide as add-on to metformin in patients with inadequately controlled type 2 diabetes. METHODS: The present study was an extension of an earlier randomized, double-blind, phase III study of dapagliflozin (n = 406) vs glipizide (n = 408) to 208 weeks (4 years). Patients continued to receive their assigned medication. No statistical treatment-group comparisons were calculated. RESULTS: At 208 weeks, dapagliflozin compared with glipizide produced sustained reductions in glycated haemoglogin (HbA1c): -0.30% [95% confidence interval (CI), -0.51 to -0.09], in total body weight: -4.38 kg (95% CI -5.31 to -3.46) and in systolic blood pressure (SBP): -3.67 mmHg (95% CI -5.92 to -1.41). The HbA1c coefficient of failure was significantly lower for dapagliflozin than for glipizide: 0.19 (95% CI 0.12-0.25) versus 0.61 (95% CI 0.49-0.72, difference -0.42; p = 0.0001). Dapagliflozin was not associated with glomerular function deterioration, while this occurred more frequently in patients in the glipizide group. Fewer patients reported hypoglycaemia in the dapagliflozin compared with the glipizide group (5.4 vs 51.5%). Genital and urinary tract infections were more common with dapagliflozin than with glipizide, but their incidence decreased with time and all events responded well to antimicrobial treatment. CONCLUSIONS: In patients completing 4 years of treatment, dapagliflozin was well tolerated and associated with sustained glycaemic efficacy and greater reductions in body weight and SBP versus glipizide.
Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glipizida/uso terapêutico , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Quimioterapia Combinada/métodos , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Infecções Urinárias/induzido quimicamenteRESUMO
The aim of the present study was to compare the long-term safety and efficacy of insulin degludec with those of insulin glargine in patients with advanced type 2 diabetes (T2D) over 78 weeks (the 52-week main trial and a 26-week extension). Patients were randomized to once-daily insulin degludec or insulin glargine, with mealtime insulin aspart ± metformin ± pioglitazone, and titrated to pre-breakfast plasma glucose values of 3.9-4.9 mmol/l (70-88 mg/dl). After 78 weeks, the overall rate of hypoglycaemia was 24% lower (p = 0.011) and the rate of nocturnal hypoglycaemia was 31% lower (p = 0.016) with insulin degludec in the extension trial set, while both groups of patients achieved similar glycaemic control. Rates of adverse events and total insulin doses were similar for both groups in the safety analysis set. During 18 months of treatment, insulin degludec + mealtime insulin aspart ± oral antidiabetic drugs in patients with T2D improves glycaemic control similarly, but confers lower risks of overall and nocturnal hypoglycaemia than with insulin glargine treatment.
Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas/efeitos dos fármacos , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Diabetes Mellitus Tipo 2/sangue , Esquema de Medicação , Quimioterapia Combinada , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Resultado do TratamentoRESUMO
AIMS: To evaluate glucose-lowering treatment strategies with linagliptin and metformin in people with newly diagnosed type 2 diabetes and marked hyperglycaemia, a prevalent population for which few dedicated studies of oral antidiabetes drugs have been conducted. METHODS: A total of 316 patients, with type 2 diabetes diagnosed for ≤12 months and with glycated haemoglobin (HbA1c) concentration in the range 8.5-12.0%, were randomized 1:1 to double-blind, free-combination treatment with linagliptin 5 mg once daily and metformin twice daily (uptitrated to 2000 mg/day maximum) or to linagliptin monotherapy. The primary endpoint was change in HbA1c concentration from baseline at week 24 (per-protocol completers' cohort: n = 245). RESULTS: The mean (standard deviation) age and HbA1c at baseline were 48.8 (11.0) years and 9.8 (1.1)%, respectively. At week 24, the mean ± standard error (s.e.) HbA1c decreased from baseline by -2.8 ± 0.1% with linagliptin/metformin and -2.0 ± 0.1% with linagliptin; a treatment difference of -0.8% (95% confidence interval -1.1 to -0.5; p <0.0001). Similar results were observed in a sensitivity analysis based on intent-to-treat principles: adjusted mean ± s.e. changes in HbA1c of -2.7 ± 0.1% and -1.8 ± 0.1%, respectively; treatment difference of -0.9% (95% CI -1.3 to -0.6; p <0.0001). A treatment response of HbA1c <7.0% was achieved by 61 and 40% of patients in the linagliptin/metformin and linagliptin groups, respectively. Few patients experienced drug-related adverse events (8.8 and 5.7% of patients in the linagliptin/metformin and linagliptin groups, respectively). Hypoglycaemia occurred in 1.9 and 3.2% of patients in the linagliptin/metformin and linagliptin groups, respectively (no severe episodes). Body weight decreased significantly with the combination therapy (-1.3 kg between-group difference; p =0.0033). CONCLUSIONS: Linagliptin in initial combination with metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycaemia, an understudied group, elicited significant improvements in glycaemic control with a low incidence of hypoglycaemia, weight gain or other adverse effects. These results support early combination treatment strategies and suggest that newly diagnosed patients with marked hyperglycaemia may be effectively managed with oral, non-insulin therapy.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Purinas/administração & dosagem , Quinazolinas/administração & dosagem , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , Hiperglicemia/sangue , Cooperação Internacional , Linagliptina , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Basal insulin analogues have a reduced risk of hypoglycaemia compared with NPH insulin, but hypoglycaemia still remains a major impediment to achieving recommended fasting plasma glucose (FPG) targets in patients with diabetes. Insulin degludec (IDeg) is a new basal insulin that forms soluble multihexamers after subcutaneous injection resulting in an ultra-long duration of action and stable glucose-lowering effect. The aim of this analysis was to compare the effect of IDeg on FPG and nocturnal confirmed hypoglycaemia as compared to insulin glargine (IGlar). METHODS AND RESULTS: Data were included from seven phase 3a, randomised, open-label, treat-to-target clinical trials in which once-daily IDeg was compared with once-daily IGlar. Two trials included a total of 957 patients with type 1 diabetes (T1D) and five trials included a total of 3360 patients with type 2 diabetes (T2D); all trials were 26 or 52 weeks in duration. Confirmed hypoglycaemia was defined as plasma glucose <3.1 mmol/L or severe episodes requiring assistance, and nocturnal hypoglycaemia occurred between 00:01 and 05:59. In all trials, the mean end-of-trial FPG was lower for IDeg than IGlar, reaching statistical significance in three trials. Similarly, IDeg was associated with a lower rate of nocturnal confirmed hypoglycaemia vs. IGlar, which was statistically significant in three trials, regardless of type of diabetes or background therapy. CONCLUSION: This analysis shows that the lower rate of nocturnal confirmed hypoglycaemia seen with IDeg relative to IGlar is accompanied by a reduced mean FPG, in particular in patients with T2D.
Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Jejum , Humanos , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: Rare endocrine-metabolic diseases (REMD) represent an important area in the field of medicine and pharmacology. The rare diseases of interest to endocrinologists involve all fields of endocrinology, including rare diseases of the pituitary, thyroid and adrenal glands, paraganglia, ovary and testis, disorders of bone and mineral metabolism, energy and lipid metabolism, water metabolism, and syndromes with possible involvement of multiple endocrine glands, and neuroendocrine tumors. Taking advantage of the constitution of a study group on REMD within the Italian Society of Endocrinology, consisting of basic and clinical scientists, a document on the taxonomy of REMD has been produced. METHODS AND RESULTS: This document has been designed to include mainly REMD manifesting or persisting into adulthood. The taxonomy of REMD of the adult comprises a total of 166 main disorders, 338 including all variants and subtypes, described into 11 tables. CONCLUSIONS: This report provides a complete taxonomy to classify REMD of the adult. In the future, the creation of registries of rare endocrine diseases to collect data on cohorts of patients and the development of common and standardized diagnostic and therapeutic pathways for each rare endocrine disease is advisable. This will help planning and performing intervention studies in larger groups of patients to prove the efficacy, effectiveness, and safety of a specific treatment.
Assuntos
Doenças do Sistema Endócrino/classificação , Endocrinologia/classificação , Doenças Raras/classificação , Relatório de Pesquisa , Adulto , Classificação , Doenças do Sistema Endócrino/diagnóstico , Endocrinologia/métodos , Feminino , Humanos , Masculino , Doenças Raras/diagnósticoRESUMO
AIMS: Durability of good glycaemic control (HbA1c ) is of importance as it can be the foundation for delaying diabetic complications. It has been hypothesized that early initiation of treatment with the combination of oral anti-diabetes agents with complementary mechanisms of action can increase the durability of glycaemic control compared with metformin monotherapy followed by a stepwise addition of oral agents. Dipeptidyl peptidase-4 inhibitors are good candidates for early use as they are efficacious in combination with metformin, show weight neutrality and a low risk of hypoglycaemia. We aimed to test the hypothesis that early combined treatment of metformin and vildagliptin slows ß-cell deterioration as measured by HbA1c . METHODS: Approximately 2000 people with Type 2 diabetes mellitus who were drug-naive or who were treated with metformin for less than 1 month, and who have HbA1c of 48-58 mmol/mol (6.5-7.5%), will be randomized in a 1:1 ratio in VERIFY, a 5-year multinational, double-blind, parallel-group study designed to compare early initiation of a vildagliptin-metformin combination with standard-of-care initiation of metformin monotherapy, followed by the stepwise addition of vildagliptin when glycaemia deteriorates. Further deterioration will be treated with insulin. The primary analysis for treatment failure will be from a Cox proportional hazard regression model and the durability of glycaemic control will be evaluated by assessing treatment failure rate and the rate of loss in glycaemic control over time as co-primary endpoints. SUMMARY: VERIFY is the first study to investigate the long-term clinical benefits of early combination treatment vs. the standard-of-care metformin monotherapy with a second agent added by threshold criteria.
Assuntos
Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hiperglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Nitrilas/uso terapêutico , Pirrolidinas/uso terapêutico , Projetos de Pesquisa , Adamantano/uso terapêutico , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Quimioterapia Combinada , Hemoglobinas Glicadas/análise , Humanos , Análise de Intenção de Tratamento , Pessoa de Meia-Idade , Obesidade/complicações , Sobrepeso/complicações , Vildagliptina , Adulto JovemRESUMO
AIM: The broadly used combination of metformin and sulphonylurea (SU) often fails to bring patients to glycaemic goal. This study assessed the efficacy and safety of vildagliptin as add-on therapy to metformin plus glimepiride combination in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control. METHODS: A multicentre, double-blind, placebo-controlled study randomized patients to receive treatment with vildagliptin 50 mg bid (n = 158) or placebo (n = 160) for 24 weeks. RESULTS: After 24 weeks, the adjusted mean change in haemoglobin A1c (HbA1c) was -1.01% with vildagliptin (baseline 8.75%) and -0.25% with placebo (baseline 8.80%), with a between-treatment difference of -0.76% (p < 0.001). Significantly more patients on vildagliptin achieved the HbA1c target <7% (28.3% vs. 5.6%; p < 0.001). The difference in fasting plasma glucose reduction between vildagliptin and placebo was -1.13 mmol/l (p < 0.001). In subgroup of patients with baseline HbA1c ≤8%, vildagliptin reduced HbA1c by 0.74% from baseline 7.82% (between-treatment difference: -0.97%; p < 0.001) with significantly more patients achieving the HbA1c target <7% (38.6% vs. 13.9%; p = 0.014). Vildagliptin was well tolerated with low incidence of hypoglycaemia, slightly higher than with placebo (5.1% vs. 1.9%) and no clinically relevant weight gain. CONCLUSIONS: Vildagliptin significantly improved glycaemic control in patients with T2DM inadequately controlled with metformin plus glimepiride combination. The addition of vildagliptin was well tolerated with low risk of hypoglycaemia and weight gain. This makes vildagliptin an attractive treatment option for patients failing on metformin plus SU particularly in patients with baseline HbA1c ≤8%.
Assuntos
Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas/efeitos dos fármacos , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Nitrilas/uso terapêutico , Pirrolidinas/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Adamantano/administração & dosagem , Adamantano/efeitos adversos , Adamantano/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/sangue , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Pirrolidinas/administração & dosagem , Pirrolidinas/efeitos adversos , Resultado do Tratamento , VildagliptinaRESUMO
AIMS: To evaluate the long-term durability of the efficacy of alogliptin compared with glipizide in combination with metformin in people with type 2 diabetes inadequately controlled on stable-dose metformin. METHODS: This multicentre, double-blind, active-controlled study randomized 2639 patients aged 18-80 years to 104 weeks of treatment with metformin in addition to alogliptin 12.5 mg once daily (n = 880), alogliptin 25 mg once daily (n = 885) or glipizide 5 mg once daily, titrated to a maximum of 20 mg (n = 874). The primary endpoint was least square mean change from baseline in HbA1c level at 104 weeks. RESULTS: The mean patient age was 55.4 years, the mean diabetes duration was 5.5 years and the mean baseline HbA1c was 7.6%. HbA1c reductions at week 104 were -0.68%, -0.72% and -0.59% for alogliptin 12.5 and 25 mg and glipizide, respectively [both doses met the criteria for non-inferiority to glipizide (p<0.001); alogliptin 25 mg met superiority criteria (p=0.010)]. Fasting plasma glucose concentration decreased by 0.05 and 0.18 mmol/l for alogliptin 12.5 and 25 mg, respectively, and increased by 0.30 mmol/l for glipizide (p < 0.001 for both comparisons with glipizide). Mean weight changes were -0.68, -0.89 and 0.95 kg for alogliptin 12.5 and 25 mg and glipizide, respectively (p < 0.001 for both comparisons with glipizide). Hypoglycaemia occurred in 23.2% of patients in the glipizide group vs. 2.5 and 1.4% of patients in the alogliptin 12.5 and 25 mg groups, respectively. Pancreatitis occurred in one patient in the alogliptin 25 mg group and three in the glipizide group. CONCLUSIONS: Alogliptin efficacy was sustained over 2 years in patients with inadequate glycaemic control on metformin alone.