Obesity is a chronic, progressive and relapsing disease with a rising global prevalence associated with increased morbidity and mortality and reduced quality of life. Treatment of obesity requires a comprehensive medical approach that includes behavioural interventions, pharmacotherapy and bariatric surgery. The degree of weight loss with all approaches is highly heterogeneous, and long‐term weight maintenance remains challenging. For years, antiobesity medications have been limited in number, often delivering meagre efficacy and raising numerous safety concerns. Therefore, there is a need for the development of highly efficacious and safe new agents. Recent insights into the complex pathophysiology of obesity have increased our understanding of intervenable targets for pharmacotherapies to treat obesity and improve weight‐related cardiometabolic complications, namely, type 2 diabetes, hyperlipidaemia and hypertension. As a result, novel potent therapies have emerged, such as semaglutide, a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) recently approved for the treatment of obesity. Semaglutide 2.4 mg once weekly significantly reduces body weight by approximately 15%, with simultaneous improvement in cardiometabolic risk factors and physical functioning in people with obesity. Tirzepatide, the first dual glucose‐dependent insulinotropic polypeptide (GIP)/GLP‐1RA, has recently demonstrated that body weight reduction exceeding 20% in people with obesity and coupled with improved cardiometabolic measures is feasible. Thus, these novel agents promise to narrow the gap between the weight‐loss effects of behaviour interventions, previous pharmacotherapies, and bariatric surgery. In this narrative review, we highlight established and emerging therapeutic treatments for long‐term obesity management and position them in a framework according to their weight loss effects.

Introduction:As the vast majority of people with type 2 diabetes (T2D) are also overweight or obese, healthcare professionals (HCP) are faced with the task of addressing both weight management and glucose control. In this narrative review, we aim to identify the challenges of reaching and maintaining body weight targets in people with T2D and highlight current and future treatment interventions.Methods: A search of the PubMed database was conducted using the search terms "diabetes" and "weight loss."Results: According to emerging evidence, treating obesity may be antecedent to the development and progression of T2D. While clinical benefits typically set in upon achieving a weight loss of 3-5%, these benefits are progressive leading to further health improvements, and weight loss of >15% can have a disease-modifying effect in people with T2D, an outcome that up to recently could not be achieved with any blood glucose-lowering pharmacotherapy. However, advanced treatment options with weight-loss effects currently in development including the dual GIP/GLP-1 receptor agonists may enable simultaneous achievement of individual glycemic and weight goals. Conclusion:Despite considerable therapeutic progress, there is still a large unmet medical need in patients with T2D who miss their individualized glycemic and weightloss targets. Nonetheless, it is to be expected that development of future therapies and their use will favourably change the scenario of weight and glucose control in T2D.

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ZUSAMMENFASSUNGDiabetes mellitus und die koronare Herzkrankheit (KHK) sind assoziierte Erkrankungen, die sich gegenseitig verstärken. Charakteristisch ist, dass sich eine KHK bei Menschen mit Diabetes auf Basis instabiler atherosklerotischer Plaques entwickelt, die in den Koronararterien zu Erosion und Ruptur neigen. Aufgrund dieser Vernetzung und des hohen kardiovaskulären Risikos bei Diabetes, wird in gemeinsamen Empfehlungen der Europäischen Gesellschaft für Kardiologie (ESC) und der Europäischen Diabetesgesellschaft (EASD) auf die Notwendigkeit hingewiesen, bei Menschen mit Diabetes frühzeitig eine Risikostratifizierung durchzuführen mit dem Ziel, individualisierte therapeutische Strategien zu implementieren. Einerseits wird ein frühzeitiges Screening nach Typ-2-Diabetes und eine Indexierung bei moderatem, hohem oder sehr hohem kardiovaskulärem Risiko angeraten, andererseits wird eine medikamentöse Behandlung von Menschen mit Diabetes und KHK oder erhöhtem kardiovaskulärem Risiko z. B. mit SGLT2-Inhibitoren (SGLT2i) und GLP-1-Rezeptoragonisten (GLP-1 RA) empfohlen.