Episode 190 - Pharmacological Treatments for Obesity with Dr Matthew Peverelle

Australians who are either overweight or obese are increasingly turning to pharmacological approaches coupled with dietary measures to achieve their weight loss goals before considering bariatric surgery.These therapies are typically considered for adults whose BMI’s are equal or above 30 kg/m2 or above 27 kg/m2 with associated comorbidities and include the following:Incretin based therapies including dual incretin agonists (most effective)Appetite suppressants-central acting drugsDopaminergic/opioid pathway modulation therapiesNutrient absorption inhibition therapiesThe most effective pharmacologic treatments available in clinical use are synthetic incretins. Natural incretins are gut derived hormones released after eating that enhance pancreatic insulin secretion in a glucose dependent manner.Examples in clinical use include: Exenatide (Byetta, a synthetic version of a peptide found in the saliva of the Gila monster lizard), Semaglutide (Ozempic-approved for type 2 diabetes, Wegovy-approved for weight loss with dosing up to 2.4mg per weekly dosing), Liraglutide (Saxenda with daily dosing). Another well-known GLP-1 is Dulaglutide (Trulicity).When applied for weight loss Semaglutide and Liraglutide lead to 10-15% body weight reduction. Benefits beyond diabetes and weight loss include a 30% reduction in the risk of heart attacks and strokes. These drugs also show promise in treating conditions such as fatty liver disease, obstructive sleep apnoea, and kidney disease.Side effects include nausea, vomiting, diarrhoea, gallstones and pancreatitis (0.2-0.3 % in most studies). They are contraindicated in patients with medullary thyroid cancer.Another incretin in clinical practice is Gastric Inhibitory Polypeptide (GIP) also known as Glucose Dependent Insulinotropic polypeptide. Like the GLP-1 incretin, GIP also stimulates insulin release in a glucose-dependent way, though it was first named for its weaker ability to inhibit stomach acid.The synthetic so called “twincretin” or dual action incretin called Tirzepatide combines GIP and GLP-1 agonist actions and further increases weight loss outcomes. Marketed as Mounjaro, clinical trials demonstrate it producing 20-22% weight loss for patients.Discontinuation rates for patients using incretin therapies for weight loss is quoted between 50-75 % in one year with factors including expense and side effects influencing this statistic. Recent data also points to significant weight regain over a two-year period after medication withdrawal.The centrally acting appetite suppressants include Phentermine which is a sympathomimetic noradrenergic agent used short term over weeks-months and increases noradrenaline and dopamine in the hypothalamus to reduce appetite. These therapies can expect an 8-12 % weight loss.Naltrexone combined with Bupropion acts on the POMC neurons reducing appetite and food cravings. Nausea, seizure activity and hypertension are side effects for a quoted 5-9 % weight loss.Orlistat is a gastrointestinal fat absorption inhibitor inhibiting pancreatic lipase and decreasing fat absorption by about 30 %. Steatorrhea and loss of fat-soluble vitamins are side effects for only 3-5 % weight loss.To discuss the application of these therapies in more depth we are joined by gastroenterologist Dr Matthew Peverelle. Matthew completed his advanced training in gastroenterology at Monash Health and Austin Health including the Victorian Liver Transplant Unit. He then continued his studies abroad completing a hepatology fellowship at the prestigious Kings College Hospital in London, subsequently he has developed a strong interest in both hepatology, luminal gastroenterology and Endo bariatrics.Thank you for joining us as he brings his expertise to the next two podcast episodes.References: Matthew Peverelle Australian Family Physician, Pharmacotherapy for obesity, Lee & Dixon Vol 46,7, July 2017 Niddk.nih.gov Obesity Evidence HubObesitymedicine.org Pmc.ncbi.nlm.nih.gov