CODDHI FOCO: DM2: As novas opções terapêuticas, glifozinas, GLP1 e IDPP4, superam as opções antigas, sulfoniluréia, metformina e insulina?

SIM: Dr Renan Montenegro (UFCE)

A explanação do Dr. Renan Montenegro focou nas novas opções de tratamento para o diabetes tipo 2 (DM2): glifozinas, agonistas de GLP-1 e inibidores de DDP4 frente as opções terapêuticas tradicionais. Inicia sua palestra mostrando que os objetivos no tratamento do DM2 são: evitar riscos (principalmente de hipoglicemias) e ganho de peso (levando a manutenção e agravamento da obesidade) e melhora da qualidade de vida. Segue sua apresentação relatando as necessidades não atendidas no tratamento do DM2: difícil controle glicêmico (principalmente da glicemia pós prandial), risco de hipoglicemia com as terapêuticas tradicionais, visão glucocêntrica (foco restrito ao controle glicêmico sem levar em consideração os benefícios de redução de outros fatores de risco cardiovascular) e ganho de peso como efeito colateral.
Apenas 46% dos pacientes com DM2 atingem alvo de hemoglibina glicada (A1c = 7%) segundo estudo multicêntrico de DM2 no Brasil. Enfatiza que as terapêuticas antigas tem um risco maior de hipoglicemia e questiona se os custos relacionados a hipoglicemia não justificariam o uso preferencial de novas drogas em populações específicas como os idosos.
Relata a importância de associação de drogas como, por exemplo, metformina com inibidores de DPP4, que pelo sinergismo de ação, aumentam o sucesso em alcançar os alvos terapêuticos. Enfatiza que apesar das novas opções terapêuticas terem menor eficácia na redução da A1c, agem em mecanismos fisiopatológicos diversos com potencias efeitos extra glicêmicos como, por exemplo, as drogas com efeito incretínico (agonista de GLP-1 e inibidor de DPP4) que poderiam ter um efeito neuro e cardioprotetor. Relata, também, as vantagens na manutenção e perda de peso associado a estas drogas e também seu possível efeito em preservar células beta pancreáticas (estudos experimentais). Comenta sobre recentes evidências ainda não comprovadas sobre o possível efeito deletério das sulfoniluréias não seletivas (glibenclamida) em pacientes com doença cardiovascular (DCV).
Na tentativa de melhorar a adesão, seria interessante uso de drogas com posologia mais simples com o objetivo de se evitar polifarmácia.
Termina sua palestra mostrando que a presença de hipoglicemia assintomática em idosos, principalmente noturna (mais comuns com as terapias tradicionais) predispõem ao aparecimento de arritmias, levando ao risco de morte súbita. Conclui que o valor de A1c ideal é o mais próximo do normal sem ocorrência de hipoglicemia significativa.

Não: Drª Lenita Zajdenverg (UFRJ)

Drª Lenita inicia sua apresentação afirmando que os estudos que comparam as novas drogas (“head to head”) com as antigas são estudos de curta duração (no máximo 1 ano) e comenta que este período seria muito limitado para avaliação de segurança cardiovascular.
Enfatiza a importância de individualização da terapêutica seguindo as tendências da farmacogenômica. Além da terapia baseada no fenótipo, provavelmente caminharemos para uma terapia baseada no genótipo, como, por exemplo, os pacientes com genótipo para o receptor SUR TCF7Lα que são resistentes ao efeito das sulfoniluréias e os pacientes com DM monogênico (MODY 1 – 3) nos quais as sulfoniluréias são a droga de escolha.
Relata um recente estudo que autoriza o uso de metformina em pacientes com taxa de filtração glomerular (TFG) superior a 60 ml/min, redução da dose em pacientes com TFG entre 45 e 60 ml/min e suspensão da metformina em pacientes com TFG inferior a 30 ml/min.
Enfatiza que os efeitos colaterais das novas drogas poderiam surgir apenas em fase pós trial (Fase 4 já liberado no mercado) como foi o exemplo da troglitazona (danos hepáticos), pioglitazona (câncer de bexiga), roziglitazona ( fraturas ósseas e insufici~encia cardíaca congestiva), agonista de GLP1 (câncer medular de tireóide, câncer de pâncreas e pancreatite), inibidor de DPP4 (risco de infecções de vias aéreas superiores).
Reforça que em termos de saúde pública as sulfoniluréias ainda são uma opção com baixo custo e efeito hipoglicemiante adequado, mas que a terapia com antidiabéticos orais deve ser individualizada.

Esta entrada foi publicada em Diabetes Tipo 2. Adicione o link permanenteaos seus favoritos.

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