New Pharmacological Treatment of Obesity: The Role of GLP-1 and Dual GIP/GLP-1 Receptor Agonists

Abstract

Obesity is a chronic, relapsing disease associated with substantial cardiometabolic, mechanical, hepatic, renal, and psychosocial complications. Although lifestyle intervention remains the foundation of treatment, pharmacotherapy is indicated when lifestyle measures alone do not provide sufficient benefit, particularly in individuals with a body mass index of at least 30 kg/m², or at least 27 kg/m² in the presence of obesity-related complications. Incretin-based therapies have transformed obesity management by producing weight loss that approaches or exceeds that achieved with some bariatric procedures. Liraglutide, once-weekly semaglutide and tirzepatide achieve weight reduction and they have shown benefits besides weight lowering effects. Treatment selection should be individualized according to expected weight loss, obesity-related complications, tolerability, contraindications, route of administration, access, cost, and patient preference. Because discontinuation is commonly followed by weight regain and reversal of metabolic improvements, incretin-based pharmacotherapy should be regarded as long-term disease-modifying treatment. Current evidence supports a complication-centered approach in which efficacy is assessed through weight, waist circumference, glycemic control, cardiovascular risk factors, functional status, and patient-reported outcomes over time.

Keywords

• Obesity
• incretin-based therapy
• GLP-1 receptor agonists
• semaglutide
• tirzepatide

Obezitenin Yeni Farmakolojik Tedavisi: GLP-1 ve İkili GIP/GLP-1 Reseptör Agonistlerinin Rolü

Abstract

Obezite; önemli kardiyometabolik, mekanik, hepatik, renal ve psikososyal komplikasyonlarla ilişkili, kronik ve tekrarlayıcı bir hastalıktır. Yaşam tarzı müdahaleleri tedavinin temelini oluşturmaya devam etmekle birlikte, bu yaklaşımların tek başına yeterli yarar sağlamadığı durumlarda farmakoterapi endikedir. Bu durum özellikle beden kütle indeksi 30 kg/m² ve üzerinde olan bireyler ile obeziteyle ilişkili komplikasyonların varlığında beden kitle indeksi 27 kg/m² ve üzerinde olan kişiler için geçerlidir. İnkretin temelli tedaviler, bazı bariatrik cerrahi yöntemlerle elde edilen kilo kaybına yaklaşan veya bunu aşan sonuçlar sağlayarak obezite tedavisinde önemli bir dönüşüm yaratmıştır. Liraglutid, haftada bir uygulanan semaglutid ve tirzepatid kilo kaybı sağlamakta ve kilo azaltıcı etkilerinin ötesinde çeşitli klinik yararlar göstermektedir. Tedavi seçimi; beklenen kilo kaybı, obeziteyle ilişkili komplikasyonlar, tolerabilite, kontrendikasyonlar, uygulama yolu, tedaviye erişim, maliyet ve hasta tercihleri doğrultusunda bireyselleştirilmelidir. Tedavinin kesilmesini sıklıkla yeniden kilo alımı ve metabolik iyileşmelerin gerilemesi izlediğinden, inkretin temelli farmakoterapi uzun süreli, hastalığın seyrini değiştirici bir tedavi olarak değerlendirilmelidir. Güncel kanıtlar, tedavi etkinliğinin zaman içinde vücut ağırlığı, bel çevresi, glisemik kontrol, kardiyovasküler risk faktörleri, fonksiyonel durum ve hasta tarafından bildirilen sonuçlar üzerinden değerlendirildiği, komplikasyon merkezli bir yaklaşımı desteklemektedir.

Keywords

• Obezite
• inkretin bazlı tedavi
• GLP-1 reseptör agonistleri
• semaglutid
• tirzepatid

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