Non-surgical interventions for obesity in type 2 diabetes: an overview
There are pros and cons to each of the non-surgical approaches designed to reduce bodyweight in people living with obesity and type 2 diabetes, and these were outlined at this year’s Diabetes UK Professional Conference.
Dietary interventions came first in a thorough and concise presentation from Dr Karl Neff, consultant endocrinologist and obesity physician at University College Dublin. The data unfortunately shows that they are not as effective as would be desired – for 90% of people, diet and exercise intervention alone is not enough for achieving durable weight loss and successful treatment of obesity.
An important point made here was that this can be because of a patient’s physiology, rather than just poor compliance. In addition, much follow-up data from RCTs is lost because people feel shame or embarrassment when they don’t achieve weight loss and drop out.
Dr Neff referred to the landmark 2018 DiRECT study, which aimed to find out whether intensive weight management within primary care would achieve remission of type 2 diabetes. Patients were given diet replacement (825-853 kcal/day formula diet for 3–5 months), stepped food reintroduction (2–8 weeks), and structured support for long-term weight-loss maintenance. The results showed that weight loss can indeed lead to remission of type 2 diabetes – almost a quarter lost 15 kg and almost a half achieved type 2 diabetes remission at one year. At two years, the weight loss had waned but type 2 remission was still around 40%.
So even though dietary intervention doesn’t work for many people, it doesn’t mean it shouldn’t be tried. Data that drew different types of intervention together found that nutritionally balanced meal replacement alongside support seems to be the most effective.
The role of pharmacotherapy
The majority of the presentation was dedicated to pharmacotherapy. First up was Orlistat, which can be a very effective agent for some people. It reduces the amount of fat absorbed from a meal and a good outcome would be a 5-10% weight loss. It’s a very safe drug and a parallel benefit is that it can reduce risk of progression from pre-diabetes to diabetes, but cons are that the gastrointestinal effects can be intolerable and it’s only effective while on the treatment.
The combination of naltrexone/bupropion can very effective in some people at around 10% weight loss. It’s not fully understood how the combination works, said Dr Neff, but it seems to work on the brain and the mechanics of appetite. It’s useful for people who want to quit smoking at the same time as bupropion is used for that. The most common effect is nausea, but others can be wide ranging and there is a long list of contraindications, such as history of bipolar disorder and uncontrolled hypertension so it’s important to take a thorough medical and psychological history. The combination is relatively new and cardiovascular safety is not established.
Liraglutide is an established diabetes treatment that’s now available as an obesity treatment in the absence of diabetes. At 3 mg (obesity dose), a 2015 study showed that, at one-year, about two thirds of people achieve over 5% weight loss, one in three that use it achieve over 10% weight loss and half of those reach over 15%. Three-year follow-up shows a persistent effect while a person is still on it. The diabetes dose of 1.8 mg does still offer some weight loss (4.7%).
Last but certainly not least was semaglutide, an existing diabetes treatment that has recently shown great promise as an obesity treatment and is expected to be licensed for that purpose in the near future. The 2021 study STEP 1, published in the New England Journal of Medicine, showed semaglutide to be a very powerful treatment for obesity.
Prior to that, a randomised phase-2 trial in 2018 comparing liraglutide and semaglutide showed the latter to be at least as effective, if not better, than liraglutide for weight reduction. It should be considered very strongly for people living with type 2 diabetes and obesity, said Dr Neff, and has additional benefits in helping to prevent cardiovascular disease and progression of renal disease. Being injectable makes it less acceptable to some and it can have gastrointestinal effects, but these are transient and usually go if people stick with therapy. If a patient is a super-responder and loses a lot of weight, there is a risk of cholecystitis, so it’s worth keeping an eye out for this.
Another important point was that patients should be treated for at least three months at full dose (or highest tolerable dose) with all of these medications and then reassessed. If they have not lost more than 5% of their bodyweight after three months then it should be stopped and, equally, if they have achieved more than 5%, the treatment should be continued.
Lastly, he touched upon the endoscopic interventions that have been studied –duodenal jejunal bypass liners (DJBL), gastric balloons and duodenal mucosal resurfacing – although kept it brief as many won’t have access to these treatments in clinical practice. They were studied with the aim of treating type 2 diabetes but some weight loss effect was also expected. With DJBL, there was weight loss and a reduction in HbA1c, but weight loss is less impressive after explantation and a significant number of people can’t tolerate implantation in the first place. The same applies with gastric balloons, which can be given sequentially with breaks, but can’t be left in. The data is not desperately convincing, according to Dr Neff, but they can be useful in some people. For duodenal mucosal resurfacing, what has been seen so far is a reduction in HbA1c but not very impressive weight loss.
The future may see combination therapy of pharmacotherapy with diet and endoscopic intervention to see if it improves outcomes.
For more on the STEP 1 and STEP 2 trials, see our coverage in Horizons.
For more on metabolic surgery, enroll on our course ‘Metabolic surgery’.
Watch out for our new course, ‘Obesity and type 2 diabetes’, coming this autumn.
The views expressed in this article are those of the author, Dr Eleanor D Kennedy.