Gastrointestinal side effects of weight loss medications

There are few true ‘breakthroughs’ in medicine, where a new treatment approach revolutionises the way a condition is treated and how people with that condition can live their lives. However, the development of novel medications for weight loss such as Tirzepatide (Mounjaro) and Semaglutide (Wegovy or Ozempic) truly merit the accolade of a revolutionary breakthrough.

Overweight and obesity are the diseases of our time, with nearly 2/3rds of adults in the UK classified as having overweight or obesity. This condition has been driven by complex changes in our food environment, activity levels, and lifestyles in the second half of the 20th century. While healthy eating, dietary weight loss strategies, and exercise are all important tools in our armoury to tackle obesity, we know that losing weight, and keeping it off, is incredibly hard for many people despite their best efforts.

Tirzepatide (Mounjaro) and Semaglutide (Wegovy or Ozempic) are a new generation of weight loss medications that mimic one of our gut hormones, called GLP-1. This is one of several hormones made in the gut lining in response to what we eat. These hormones control how the gut moves, the secretions of bile and from the pancreas, how our stomach empties, and, importantly for these medications, our appetite.

The clinical trials of Tirzepatide and Semaglutide show that these injections can lead to substantial weight loss, around 15-20% of body weight for the average person in the trial, and can improve type 2 diabetes, obstructive sleep apnoea, and a whole host of weight-related conditions and complications. This can be truly life-changing for people affected.

However, Tirzepatide (Mounjaro) and Semaglutide (Wegovy or Ozempic) can cause side effects, most commonly gastrointestinal. GLP-1 has complex effects on the gut, including how the stomach empties, how fast the small intestine moves food, when the gallbladder and pancreas release their secrections, and how the colon moves and the bowels open. It also has effects on satiety (fullness). Therefore these medications have a similar complex effect on the gut.

Nausea is the most common symptom on these medications, affecting up to half of patients taking higher doses. This is generally mild, but in 20% of patients can be moderate or severe, and associated with vomiting and reflux. Some of this effect is due to the drug causing satiety or fullness, and some of the effect is due to the medication slowing down the emptying of the stomach (called delayed gastric emptying or gastroparesis). This can lead to excessive fullness, and increased problems with heartburn and reflux.

Diarrhoea and constipation are also common side effects, caused by how the drugs change how the bowel moves and how secretions are released into the bowel. There can also be issues with more significant problems with the gallbladder and pancreas gland, either related to weight loss, or the medications itself.

There are two important considerations regarding these symptoms, how to control them to allow people to continue on their weight loss journey, and to ensure there is no other, worrying cause of new symptoms. For instance a change in bowel habit or new, worsening reflux are symptoms that require assessment before attributing them to medication side effects, as they can be a sign of serious underlying conditions. Expert guidance from a gastroenterologist and a dietitian can be helpful to determine if further investigations are needed, and how best to control symptoms so that a patient can continue on the medications to achieve their weight loss goals.