Colesevelam e Complicações do Diabetes

Efficacy and Safety of Colesevelam in Patients With Type 2 Diabetes Mellitus and Inadequate Glycemic Control Receiving Insulin-Based Therapy . Ronald B. Goldberg, MD; Vivian A. Fonseca, MD; Kenneth E. Truitt, MD; Michael R. Jones, PhD Arch Intern Med. 2008;168(14):1531-1540.
Background Poor glycemic control is a risk factor for microvascular complications in patients with type 2 diabetes mellitus. Achieving glycemic control safely with insulin therapy can be challenging.
Methods A prospective, 16-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study conducted at 50 sites in the United States and 1 site in Mexico between August 12, 2004, and December 28, 2005. Subjects had type 2 diabetes mellitus that was not adequately controlled (glycated hemoglobin level, 7.5%-9.5%, inclusive) receiving insulin therapy alone or in combination with oral antidiabetes agents. In total 287 subjects (52% men; mean age, 57 years; with a mean baseline glycated hemoglobin level of 8.3%) were randomized: 147 to receive colesevelam hydrochloride, 3.75 g/d, and 140 to receive placebo.
Results Using the least squares method, the mean (SE) change in glycated hemoglobin level from baseline to week 16 was –0.41% (0.07%) for the colesevelam-treated group and 0.09% (0.07%) for the placebo group (treatment difference, –0.50% [0.09%]; 95% confidence interval, –0.68% to –0.32%; P < .001). Consistent reductions in fasting plasma glucose and fructosamine levels, glycemic-control response rate, and lipid control measures were observed with colesevelam. As expected, the colesevelam-treated group had a 12.8% reduction in low-density lipoprotein cholesterol concentration relative to placebo (P < .001). Of recipients of colesevelam and placebo, respectively, 30 and 26 discontinued the study prematurely; 7 and 9 withdrew because of protocol-specified hyperglycemia, and 10 and 4 withdrew because of adverse events. Both treatments were generally well tolerated.
Conclusions Colesevelam treatment seems to be safe and effective for improving glycemic control and lipid management in patients with type 2 diabetes mellitus receiving insulin-based therapy, and it may provide a novel treatment for improving dual cardiovascular risk factors

TINSAL-T2D

Diabetes Care. 2008 Feb;31(2):289-94.

Salsalate improves glycemia and inflammatory parameters in obese young adults.
Fleischman A, Shoelson SE, Bernier R, Goldfine AB.
Harvard Medical School, Boston, Massachusetts, USA.
OBJECTIVE: Sedentary lifestyle and a western diet promote subacute-chronic inflammation, obesity, and subsequently dysglycemia. The aim of the current study was to evaluate the efficacy of the anti-inflammatory drug salsalate to improve glycemia by reducing systemic inflammation in obese adults at risk for the development of type 2 diabetes. RESEARCH DESIGN AND METHODS: In a double-masked, placebo controlled trial, we evaluated 20 obese nondiabetic adults at baseline and after 1 month of salsalate or placebo. RESULTS: Compared with placebo, salsalate reduced fasting glucose 13% (P <>

Targeting INflammation Using SALsalate in Type 2 Diabetes (TINSAL-T2D)This study is ongoing, but not recruiting participants.
Sponsors and Collaborators:
Joslin Diabetes CenterNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by:
Joslin Diabetes Center
ClinicalTrials.gov Identifier:
NCT00392678

Business Week: Número necessário para tratar

A revista Business Week há três semanas lançou na capa matéria questionando a prescrição indiscrimina do Lipitor, a atorvastatina, da Pfizer para redução do colesterol. Há dois dias a matéria foi liberada na página da revista e, reproduzida aqui.

O mais importante do artigo é clicar na tabela que vem logo à frente para ler o NNT, ou number need to treatment, que em português continua sendo NNT, ou seja o número de pacientes que preciso tratar para que um evento seja prevenido.

Apesar das recomendações de acadêmicos, a maioria dos artigos não apresenta o NNT, somente a redução relativa obtida com o medicamento versus o placebo.

Tratamento do diabetes em debate: estréia "Clínica e Epidemiologia"

Anunciou-se agora a suspensão do ensaio clínico em diabéticos, ACCORD.

NEJM publicou os resultados do Steno-2 realizado na Dinamarca.

O debate é muito interessante: o controle de glicemia é realmente o que vale para prevenir a doença cardiovascular no diabético tipo 2. Ou somente reduzir a pressão e elevar o HDL-colesterol já basta(m)?

Leia você mesmo, o resultado do Steno-2, o delineamento e a notícia de suspensão do Accord nas páginas de "Clínica e Epidemiologia".

A reposição hormonal: nada de novo no front.

Ontem, JAMA publicou mais uma análise do ensaio clínico Women´s Health Initiative. Essa pesquisa foi aplicada em dois tipos diferentes de mulheres: com e sem útero para testa a combinação estrógeno-progestágeno ou somente estrógeno, respectivamente. Os resultados iniciais publicados em 2002 encerraram a carreira da reposição hormonal como prevenção de doença cardiovascular e, ao contrário do que se pensa não contra-indicaram o uso restrito por pouco tempo no início do climatério. O estudo publicado ontem faz uma "mistura" das duas populações para verificar se o uso precoce, próximo à menopausa, não seria protetor, principalmente em mulheres mais jovens. O resultado foi que não há risco para mulheres que começam o uso próximo da menopausa para doença coronariana. Porém, há risco maior de doença cerebrovascular. Porém, os press release somente enfatizam o fato que não há risco de doença coronariana mas, simplesmente não noticiam o aumento de risco da doença cerebrovascular. Como se sofrer um acidente cerebral fosse uma questão menor em relação a ter um infarto do miocárdio. Abaixo, o resumo publicado em JAMA, com destaque para a permanência de risco de doença, não interessa se na coronária ou na carótida.

Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause
Jacques E. Rossouw, MD; Ross L. Prentice, PhD; JoAnn E. Manson, MD, DrPH; LieLing Wu, MSc; David Barad, MD; Vanessa M. Barnabei, MD, PhD; Marcia Ko, MD; Andrea Z. LaCroix, PhD; Karen L. Margolis, MD; Marcia L. Stefanick, PhD JAMA. 2007;297:1465-1477.
Context The timing of initiation of hormone therapy may influence its effect on cardiovascular disease. Objective To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began.
Design, Setting, and Participants Secondary analysis of the Women's Health Initiative (WHI) randomized controlled trials of hormone therapy in which 10 739 postmenopausal women who had undergone a hysterectomy were randomized to conjugated equine estrogens (CEE) or placebo and 16 608 postmenopausal women who had not had a hysterectomy were randomized to CEE plus medroxyprogesterone acetate (CEE + MPA) or placebo. Women aged 50 to 79 years were recruited to the study from 40 US clinical centers between September 1993 and October 1998. Main Outcome Measures Statistical test for trend of the effect of hormone therapy on coronary heart disease (CHD) and stroke across categories of age and years since menopause in the combined trials. Results In the combined trials, there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 379 cases of CHD and 239 cases of stroke in the placebo group. For women with less than 10 years since menopause began, the hazard ratio (HR) for CHD was 0.76 (95% confidence interval [CI], 0.50-1.16); 10 to 19 years, 1.10 (95% CI, 0.84-1.45); and 20 or more years, 1.28 (95% CI, 1.03-1.58) (P for trend = .02). The estimated absolute excess risk for CHD for women within 10 years of menopause was –6 per 10 000 person-years; for women 10 to 19 years since menopause began, 4 per 10 000 person-years; and for women 20 or more years from menopause onset, 17 per 10 000 person-years. For the age group of 50 to 59 years, the HR for CHD was 0.93 (95% CI, 0.65-1.33) and the absolute excess risk was –2 per 10 000 person-years; 60 to 69 years, 0.98 (95% CI, 0.79-1.21) and –1 per 10 000 person-years; and 70 to 79 years, 1.26 (95% CI, 1.00-1.59) and 19 per 10 000 person-years (P for trend = .16). Hormone therapy increased the risk of stroke (HR, 1.32; 95% CI, 1.12-1.56). Risk did not vary significantly by age or time since menopause. There was a nonsignificant tendency for the effects of hormone therapy on total mortality to be more favorable in younger than older women (HR of 0.70 for 50-59 years; 1.05 for 60-69 years, and 1.14 for 70-79 years; P for trend = .06).
Conclusions Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause, but this trend test did not meet our criterion for statistical significance. A similar nonsignificant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause. These data should be considered in regard to the short-term treatment of menopausal symptoms.

Medicamento falha, Wall Street Journal noticia.

Uma proposta revolucionária para as doenças cardíacas, o AGI-1067 (quem quiser assistir um filme fantástico sobre aterosclerose e a ação desse fármaco, acesse http://www.atherogenics.com) não teve sucesso na sua tentativa de reduzir morte e reinfarto do miocárdio. Uma pena. Esse fato ocorre a todo momento na pesquisa farmacêutica, mas cada vez mais a notícia chega pela imprensa econômica. O estudo deverá ser apresentado daqui há 8 dias em Nova Orleans, no congresso do colégio americano de cardiologia, mas hoje já sabemos do resultado pelo The Wall Street Journal.(abaixo a notícia) Talvez, esteja respondendo a uma pergunta de um amigo que questiona porque assino o WSJ e, compareço a poucos congressos. Esse é um dos motivos, a notícia chega antes, outro é que as transmissões à distância pela internet estão cada vez melhores e, a baixíssimo custo.

AtheroGenics Says Heart DrugMisses Primary Trial Target
By RON WINSLOWMarch 19, 2007 7:56 a.m.
AtheroGenics Inc. said its heart drug AGI-1067 failed to reach its primary goal in a 6,127-patient clinical trial, but that it did reduce a combination of cardiovascular death, heart attack and stroke.
The Alpharetta, Ga.-based company announced the preliminary findings this morning just eight days before scientists are scheduled to present more complete data at next week's meeting of the American College of Cardiology in New Orleans. Under the college's embargo rules, the company is forbidden from disclosing further details of the study until then.
"We're obviously disappointed we didn't meet the primary endpoint," said Russell Medford, president and chief executive officer of AtheroGenics, "but we are optimistic about the results of the trial and we do look forward to continuing development of what we think is an important drug with the goal of improving patient care."
AGI-1067 is a drug with both anti-inflammatory and antioxidant activity that the company is developing to prevent serious cardiovascular events in people at risk of heart disease.
Analysts have generally been skeptical that the drug would achieve its primary target, though many viewed it as a potential blockbuster if it did. The drug's fate likely depends on further details from the study, including the statistical strength of the possible benefits the company described.
The primary endpoint, as the main goal of a clinical trial is called, included cardiovascular death, resuscitated cardiac arrest, nonfatal heart attacks, need for bypass surgery or angioplasty to clear blocked arteries, and urgent hospitalization for acute chest pain. Patients in the trial all had a history of heart disease and all were being treated with a variety of other heart drugs, including cholesterol-lowering drugs called statins.
"We have a wealth of information that we're going through," Dr. Medford said in an interview this morning. "What we've seen is encouraging and we have determined that further development of the drug is important."
Whether that will require additional clinical studies isn't clear. Decisions will involve AstraZeneca PLC, which has a joint venture with AtheroGenics, and which will have 45 days once analysis of the data is complete, to determine whether to continue the relationship. The company also plans to hold discussions with the Food and Drug Administration.

NEJM arma um terreno minado: vários estudos sobre stent coronariano

The New England Journal of Medicine adiantou a sua edição de 13 de março apresentando seis artigos sobre a discussão sobre o melhor tipo de stent coronariano. O editorial escrito pelo próprio editor Jeffrey Drazen é um primor de tucanagem científica. Mas, parabéns a ele por ter apresentado tantos pontos de vista e, nos deixado confuso. Afinal, ciência é dissenso e, quem gosta de consenso que vá para a igreja ou viver em Cuba, Líbia, e quetais.

A revista armou um terreno minado com mais de um artigo analisando o mesmo banco de dados. Talvez, no feriado de carnaval consiga andar na ponta do pé e, tentar desarmar as armadilhas que cada autor colocou nos textos.

Já discuti bastante esse tema anteriormente. Amanhã, publicarei o impacto na mídia. Vamos ver o que acontecerá com as ações dos dois principais fabricantes do stent farmacológico: a J&J e a Boston Scientific.

Por ser assinante e, com o cookie,não consigo identificar se os artigos estão liberados para acesso livre em http://www.nejm.org