EASO GRADE-Based Framework for the Pharmacological Treatment of Obesity and its Complications

Hi, my name is Barbara McGowan and I'm a consultant and professor of endocrinology and diabetes at Guy's and St. Thomas' Hospital in London.

In this 5-minute CPD, I'm going to share the key principles of the new European Association for the Study of Obesity's treatment algorithm for pharmacological management of obesity and its complications. So let's get started.

Obesity is a chronic, adiposity-based disease driven not just by behavioural factors but by biology. hormonal dysregulation, neuroendocrine pathways and genetic predisposition all contribute. Behavioural changes remain an important intervention in obesity care, but there are new pharmacotherapy options that can complement and facilitate behavioural interventions. The ASU Pharmacological Treatment Algorithm provides guidance for clinicians on the pharmacological management of obesity, with treatment decisions directed not only toward weight reduction, but also the management of obesity-related complications.

The EASO algorithm draws on a network meta-analysis comparing six medications that have been approved by the European Medicines Agency for obesity treatment in adults or adopted in at least one member EASO country. These medications are Olestat, Naltrexone in combination with bupropion, Liraglutide, Fentamine in combination with Topiramate, Semaglutide and Trezepatide.

Our team analysed 56 long-term trials up until 31 January 2025 with over 60,000 participants to assess the effectiveness of obesity medication for the algorithm. Across the board, all of these medications were superior to placebo in reducing body weight. With a magnitude varied, semaglutide and terzapotide consistently achieved greater than 10% total body weight reduction. But here's the crucial shift. The algorithm emphasizes tailoring treatment to obesity-related complications, not just weight reduction. Semaglutide reduces major adverse cardiovascular events, or MACE, and is associated with a lower risk of all-cause mortality.

It is the only obesity management medication, or OMM, with RCT-proven cardiovascular outcome benefit in people with established cardiovascular disease. Semaglutide also improves outcomes in knee osteoarthritis. seems to offer glycemic benefits and some cardiovascular advantage in at-risk patients, though it is less potent than newer treatments like semaglutide. Terzapotide shows efficacy in obstructive sleep apnea and metabolic steator hepatitis. Both agents, that is semaglutide and terzapotide, improve glycemic control, restore normal glycemia and in some cases drive type 2 diabetes remission. The safety profile of these newer medications is reassuring. Most medications did not increase serious adverse events compared to placebo, with the exception of naltrexone in combination with bupropion in patients with uncontrolled hypertension.

But here's the challenge.

Discontinuation often leads to significant weight regain up to 67% within a year. This reinforces the principle that obesity, like hypertension or diabetes, requires chronic management. These medications are not short-term fixes.

So how do we apply this?

The ACEL algorithm suggests, firstly, we start with behavioural interventions for all. Secondly, we add pharmacotherapy early, especially when complications are present. Thirdly, we choose the medication based on the patient's obesity-related complications profile. Subpatients, of course, will need to be considered for bariatric surgery, but this is outside the scope of the algorithm. This tailored approach ensures that we're not just targeting weight but improving long-term health outcomes.

In summary, the new IASA pharmacotherapy algorithm represents a paradigm shift. Obesity pharmacotherapy is not only about weight reduction but about matching the right medication to the right complication. I am Barbara Magão for 5-Minute CPD. Thanks for watching. Be sure to check out additional resources on this page and more learning at eeso.org.