An all-too-common comorbidity for those suffering with bipolar disorder (BP) is excessive weight and associated metabolic issues. While weight issues seem to be an inherent part of the disease course in untreated or treated BP, many of the commonly prescribed psychotropic medications for BP have adverse metabolic effects that can greatly compound the issue and lead to treatment nonadherence. Not only can obesity, and obesity-associated issues such as cardiovascular disease and diabetes, greatly increase morbidity and mortality in patients with BP, it can worsen the disease course and patient quality of life. Although improvements in lifestyle choices (e.g., diet and exercise) are encouraged, they are often difficult to implement and/or ineffective for patients with BP.

Glucagon-like peptide-1 (GLP-1) is a peptide secreted by the intestines in response to nutrient intake; it suppresses appetite by binding to receptors in the hypothalamus and other energy-regulating areas of the brain. The GLP-1 receptor agonist, luraglutide, has been shown to be safe and effective in reducing weight in psychiatrically healthy individuals and is FDA-approved for use in those who are obese (BMI=30 kg/m2) or who are overweight (BMI=27 kg/m2) with at least 1 weight-related comorbid condition such as hypertension or type 2 diabetes.

In this 40-week, randomized, placebo-controlled, double blind, parallel-group study by McElroy and colleagues, obese (or overweight with =1 related comorbidity) participants (n=60; age 18-65 years old) with stable type I or II BP (defined as those scoring within normal to mildly ill ranges on the Clinical Global Impression BD Severity Scale (CGI-BP-Severity), the Young Mania Rating Scale (YMRS), and the Montgomery Asberg Depression Scale (MADRS) and with absence of significant suicidality or psychosis) were treated with subcutaneous liraglutide or placebo (targeted to 3.0 mg/day) in addition to nutrition and lifestyle counseling. At the end of 40 weeks, participants treated with liraglutide demonstrated significant reductions in weight (as well as BMI, hemoglobin A1C levels, and Three Factor Eating Questionnaire hunger subscale and Binge Eating Scale scores) whereas placebo-treated individuals experienced some small weight gain (Figure).

The liraglutide-induced weight loss occurred regardless of concomitant treatment with potentially weight-increasing antipsychotics. Importantly, there were no liraglutide-related adverse effects in terms of worsening psychiatric symptoms (as evidenced by no significant changes from baseline in CGI, YMRS, and MADRS scores or suicidal or psychotic symptom emergence). Both liraglutide- and placebo-treated groups experienced minor gastrointestinal side effects; however, quite interestingly, such side effects were more prevalent in the placebo treated group and discontinuation due to adverse effects occurred in significantly more placebo-treated patients vs. liraglutide-treated patients (n=11 vs. 3).

Although these data are based on a somewhat small study, they are extremely promising in terms of safely and effectively mitigating the negative impact of overweight and obesity on morbidity, mortality, quality of life, and general outcomes for patients with BP using GLP-1 agonists.

Reference:
McElroy SL et al. J Clin Psychopharmacol 2024; Epub ahead of print. Abstract