Can we use obesity medications in combination?

We very commonly use combinations of medications to treat chronic medical conditions like type 2 diabetes and hypertension (high blood pressure). The obesity field is still in its infancy, with few medication choices, and little in the way of study of medications together.

Of the three medications available for weight management in Canada, naltrexone/bupropion (NB) (trade name Contrave), and liraglutide 3.0mg (trade name Saxenda) are the most commonly utilized. Liraglutide is one of a class of medications called GLP1 receptor agonists (GLP1RA). While liraglutide 3.0mg is the only GLP1RA currently approved in Canada for weight management, there are many GLP1RAs that are in use as type 2 diabetes treatments.

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A recent study evaluated data on the efficacy and safety of NB in people with type 2 diabetes already on a GLP1RA. The authors, led by Dr. Sean Wharton, evaluated data from the LIGHT trial, which was the cardiovascular outcome trial of the obesity medication naltrexone/bupropion (NB) (trade name Contrave). As blogged previously, the LIGHT study was halted about halfway through because interim data had been released, with the concern being that this data release could impact the integrity of that trial. The study we are discussing today was a post hoc analysis of NB vs placebo amongst people in the LIGHT trial with type 2 diabetes who were on stable treatment with an incretin agent (either a GLP1RA or DPP4 inhibitor) prior to randomization in the trial. Today we will focus on the results for people on a GLP1RA.

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Amongst the 655 patients in the trial with type 2 diabetes already on GLP1RAs, mean weight loss was significantly greater (-5.2%) amongst people taking NB vs placebo. There were no significant differences in effectiveness of NB in people on GLP1RA vs not on GLP1RA in any of the analyses. Serious adverse events were reported by 12.4% of people on NB and GLP1RA , vs 11.1% of people on placebo and GLP1RA (ie very similar).

It makes sense that combination treatment could provide greater weight loss than one medication alone. The available obesity medications have different mechanisms of action, so it is entirely sensible to think that using multiple medications may provide greater weight loss than one medication alone. We can think about hypertension (high blood pressure) in a similar way – multiple medications are often needed to control blood pressure, and we choose medications that work in different ways to provide better blood pressure control than one medication alone.

The current study has its limitations which include (for scientists in the audience): post hoc analysis; weight loss achieved previously on GLP1RA before trial not known; metabolic parameters like change in A1C not available. Also, people in this study were on a variety of different GLP1RA formulations for treatment of diabetes, some of which cause more weight loss than others. They were also on GLP1RA at a treatment dose for diabetes, lower than dosing used for weight management (in the case of liraglutide, which is 1.2mg or 1.8mg as a diabetes treatment (Victoza), vs 3.0mg as an obesity treatment (Saxenda).

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BOTTOM LINE: This study shows that naltrexone/bupropion as an obesity treatment is effective and safe in addition to GLP1RA treatment in people with type 2 diabetes.

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