[Peptide hormone analogue-based pharmacotherapy for obesity is effective : What is the evidence on hard end points and the long-term course?]

The anorectic peptide-based obesity management medications (OMM) have dominated the treatment of obesity over the last decade. This review analyses the evidence that has laid the ground for the three most frequently used drugs (liraglutide, semaglutide and tirzepatide) with regulatory approval. In this context, the SCALE program investigated liraglutide for weight loss and found its effectiveness to be roughly 6-8%. Similarly, the STEP program extensively researched semaglutide as a weight loss intervention and found it to be effective in reducing body weight by 9.6% in people with type 2 diabetes and by 15% in those without. Likewise, for tirzepatide this evaluation was done under the SURMOUNT program, which reported an efficacy of 14.7% in body weight reduction for type 2 diabetes patients as opposed to 22.1% in people without diabetes. The positive effects usually diminish when treatment is discontinued. The SELECT trial provided the first concrete evidence of risk reduction of major adverse cardiovascular events (MACE) by 20% with the use of semaglutide. Overall, safety and tolerability of these 3 drugs is generally good across all studies. Additionally, the most common adverse events reported are gastrointestinal, which occur early during treatment and subside over time. Data on other hard end points and long-term outcomes do not yet exist.