Mounting evidence, including the recent (and unprecedented) phase 2 data on retatrutide, supports a role for incretin hormone agonists in treating obesity. But with great power comes great responsibility.
…Several incretin (gut-secreted hormone) pathways are now being explored therapeutically for obesity, diabetes and other obesity-related metabolic conditions (for example, non-alcoholic steatohepatitis and heart failure). Retatrutide, the first triple-incretin agonist, has just completed its phase 2 development programme. The two studies that composed the phase 2 programme included adults who are overweight or have obesity1, with or without type 2 diabetes2. These studies were reported in recent issues of the New England Journal of Medicine and The Lancet, respectively. The level of weight loss achieved in these studies has generated justifiable excitement. Along with recent encouraging results from other incretin agonists, these drugs are poised to dramatically change how obesity is treated.
…Head-to-head studies that compare obesity pharmacotherapies have not been conducted.
…Incretin agonists seem to be well tolerated, with the most frequent adverse events being gastrointestinal—including nausea, vomiting, diarrhea or constipation. In all studies that evaluate the weight-loss effects of incretin agonists, the proportion of people who stopped treatment was lower in the active medication arms than in placebo arms, reflecting a positive risk/benefit ratio of these agents despite their known side effects. Retatrutide appeared to be no different, with mild-to-moderate gastrointestinal adverse events reported in 13–50% of participants.
…A rich therapeutic line-up also fuels competition, which ultimately benefits patients in multiple ways. First, competition stimulates discovery and ongoing efforts to improve on existing products. Second, concerns regarding drug availability should decrease as the number of therapeutic options increases. Third, competition should positively impact pricing, therefore increasing access to these treatments to more people in need, minimizing disparities that are particularly prevalent in this field.