The treatment of
obesity can no longer be reduced to a simplistic view of
weight loss. Metabolic adaptation leads to systematic weight regain following
weight-loss efforts, and new
obesity treatments should therefore aim to induce long-standing double-digit
weight loss, and thus improve and even reverse
obesity-associated comorbidities such as
type 2 diabetes. Until now, only
metabolic surgery has been able to achieve such a goal, but this invasive procedure cannot be offered on a large scale. Among the alternatives, lifestyle interventions and
drug therapies have often been disappointing. The recent availability of once-weekly subcutaneous 2.4 mg
semaglutide (a
glucagon-like peptide-1 receptor agonist; Wegovy™ Novo Nordisk A/S, Bagsværd, Denmark) has changed the scene, and
semaglutide is considered a 'game changer' in the treatment of
obesity. The results from the phase III STEP (
Semaglutide treatment effect in people with
obesity) clinical programme have shown that
semaglutide provides clinically meaningful and sustained
weight loss in ranges much higher than those achieved with previously available
pharmacotherapies. These results led to the approval of
semaglutide by regulatory authorities as an adjunct to a reduced-calorie diet and increased physical activity in people with
obesity or
overweight, with at least one weight-related comorbidity. With data from phase II and III clinical trials showing that newer drugs (i.e. the
glucagon-like peptide-1 and
gastric inhibitory polypeptide dual receptor agonist
tirzepatide and the
amylin agonist
cagrilintide, either alone or combined) produce a greater sustained
weight loss than
semaglutide, an upstream 'weight-centric' strategy has emerged as a new standard for the treatment of
type 2 diabetes.