Better weight loss results with GLP-1 analogs and bupropion/naltrexone combination

In a recent study published in International Journal of ObesityResearchers examined the effects of combined glucagon-like peptide 1 (GLP-1) analog and bupropion/naltrexone treatment on weight loss.

Clinical Research: Effect of combined GLP-1 analog and bupropion/naltrexone on weight loss: a retrospective cohort study.  Image Credit: millf/ShutterstockClinical Research: Effect of combined GLP-1 analog and bupropion/naltrexone on weight loss: a retrospective cohort study., Image Credit: millf/Shutterstock

Obesity is associated with many complications, such as high blood pressure, diabetes, osteoarthritis, cancer, cardiovascular death and premature death. Adapted diet and exercise are integral to the treatment of obesity; However, changes in health behavior alone are usually unstable or insufficient, requiring pharmacologic therapy. Many effective and safe medicinal treatments that promote weight loss and weight control have been introduced.

GLP-1 inhibits agouti-related peptide and hypothalamic neuropeptide Y for homeostatic appetite regulation, reducing appetite and increasing satiety. One trial reported that a 1 mg weekly dose of semaglutide (GLP-1 analog) was associated with a 6 kg weight loss in patients with diabetes. Bupropion inhibits noradrenaline and dopamine reuptake, while naltrexone is an opioid antagonist of the mesolimbic reward pathway, which reduces reward/pleasure-based or hedonic appetite.

One study showed that naltrexone and bupropion treatment was associated with a 5.2% reduction in total body weight (TBWL). The combination of these treatments that target mesolimbic hedonic appetite and hypothalamic appetite regulation may synergistically affect weight loss. Nevertheless, the predictive effects of combined GLP-1 analog and bupropion/naltrexone treatment on weight loss remain undefined.

about the study

In the current study, researchers determined the effects of combined GLP-1 analog and bupropion/naltrexone treatment on weight loss in obese patients. Adults aged ≥ 19 with a body mass index (BMI) ≥ 30 kg/m2 This included attending a clinic in Vancouver if they were prescribed a GLP-1 analog for obesity and having a follow-up visit at six months.

Individuals who received bupropion/naltrexone before GLP-1 analog therapy and those who received surgical treatment for obesity before or during the study were excluded. Participants received lifestyle recommendations through counseling sessions or educational materials. Data were collected on the use and dosage of the GLP-1 analogs, bupropion and naltrexone.

In addition, data were obtained on other medications related to weight loss, such as sodium-glucose cotransporter-2 inhibitors, diuretics, and orlistat. Information on age, sex, hypertension, diabetes, dyslipidemia, smoking, alcohol consumption, depression, anxiety, and immobility was collected at baseline. Baseline characteristics were compared by pharmacotherapy, i.e., GLP-1 analog therapy alone or combined with bupropion/naltrexone.

For GLP-1 analog monotherapy patients, percent TBWL was calculated from baseline to six and 12 months. In contrast, for patients on combination therapy, bupropion/naltrexone add-on was estimated at six and 12 months from the start of treatment. Responders were those who had ≥ 5% TBWL to GLP-1 analogs; Non-responders were those with TBWL less than 5%. A linear regression model examined the relationship between the use of combined therapy and percent TBWL relative to monotherapy; Analyzes were repeated after adjusting for baseline BMI, age, and gender differences.

test result

In total, 415 participants were included for analysis. More than three-quarters of the subjects were women; Most individuals had BMI ≥ 40 kg/m2, Participants were followed up for an average of about 511 days. All subjects were started on GLP-1 analog monotherapy, and 22.9% were started on add-on treatment (bupropion/naltrexone). Comorbidities were similar between patients receiving GLP-1 analog monotherapy and combination therapy.

However, patients on the combination therapy were less likely to have diabetes and more likely to have polycystic ovarian syndrome. On average, monotherapy and combination therapy patients visited 7.7 and 6.1 physicians, respectively, within the first year. Add-on treatment was initiated 150.4 and 293.6 days after initiation of GLP-1 analog monotherapy among responders and non-responders, respectively.

At one year, GLP-1 analog monotherapy recipients lost an average of 11.42 kg, while patients receiving the combination therapy lost an average of 5.51 kg. The average percent TBWL among respondents was 4.3% at six months and 5.3% at 12 months after add-on introduction. The corresponding estimates among non-responders were 3.7% and 4%, respectively.

No significant difference in percent TBWL was observed between monotherapy and combination therapy patients. Nevertheless, a significant difference was evident when stratified by GLP-1 analog response; Compared with GLP-1 analog monotherapy alone, combination therapy was significantly associated with a higher percentage of TBWL in responders and non-responders. These differences persisted even after adjusting for age, sex and BMI.


In summary, the findings suggest that adding bupropion/naltrexone therapy to GLP-1 analog monotherapy reduces excess weight, even in those with an initially poor response to monotherapy. The reduction in excess weight with bupropion/naltrexone was 4% to 5%. However, these results require confirmation in randomized controlled trials.

Journal Reference:

  • Naude J, Zentner A, Suresh P, Bittman J, Khan NA. Effect of combined GLP-1 analog and bupropion/naltrexone on weight loss: a retrospective cohort study. Int J Obes2024, DOI: 10.1038/s41366-024-01526-2,

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