Is it Time to Expand Glucagon-like Peptide-1 Receptor Agonist Use for Weight Loss in Patients Without Diabetes?

Updike, Wendy H.; Pane, Olivia; Franks, Rachel; Saber, Faizah; Abdeen, Farah; Balazy, Derek; Carris, Nicholas W.

doi:10.1007/s40265-021-01525-x

Cited by 14 publications

(9 citation statements)

References 36 publications

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“…15 In our analysis, patients receiving a GLP-1 RA without an antidepressant were observed to have weight loss similar to what would be expected based on other studies. 15 However, given the real-world data set used in our analysis, it should be considered that the observed effect of the GLP-1 RA on weight loss is impacted by these differences between agents, and further may have been diminished due to medication nonadherence. Indeed, nonadherence to GLP-1 RAs is more common versus noninjectable antidiabetic medications, [16][17][18] and poor adherence to GLP-1 RAs is associated with significantly less weight loss compared with high adherence.…”

Section: Discussionsupporting

confidence: 85%

“…13,14 There are notable differences between GLP-1 RA agents, long- versus short-acting, standard versus high doses, potency, and the resultant effect on weight loss which is impacted by type 2 diabetes status. 15 In our analysis, patients receiving a GLP-1 RA without an antidepressant were observed to have weight loss similar to what would be expected based on other studies. 15 However, given the real-world data set used in our analysis, it should be considered that the observed effect of the GLP-1 RA on weight loss is impacted by these differences between agents, and further may have been diminished due to medication nonadherence.…”

Section: Discussionsupporting

confidence: 85%

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Effect of Antidepressants on Glucagon-Like Peptide-1 Receptor Agonist-Related Weight Loss

Durell

Franks

Coon

et al. 2022

Journal of Pharmacy Technology

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Background: Depression and obesity have a bidirectional relationship making the management of one, without the other, problematic. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a preferred medication class for diabetes and obesity treatment given their weight loss effect; however, it is not known how antidepressants impact this effect. Objective: To assess the impact of antidepressant use on GLP-1 RA-associated weight loss in patients with or without type 2 diabetes mellitus. Methods: This was a retrospective, propensity matched, cohort study conducted using TriNetX. The study identified patients initiating a GLP-1 RA being treated with citalopram/escitalopram, bupropion, or no antidepressant. Cohorts were propensity score matched to analyze the primary outcome of mean end-of-study (77-371 days) body weight. Results: An initial query identified 31 273 patients eligible for analysis (30 160 receiving no antidepressant, 311 receiving bupropion, and 802 receiving citalopram/escitalopram). After propensity score matching, the study found patients receiving citalopram/escitalopram were taking more antidiabetic therapies at baseline compared with patients not treated with an antidepressant. Patients in the antidepressant cohorts experienced less weight loss compared with their respective matched cohorts not receiving antidepressants (citalopram/escitalopram −0.73 kg versus −1.74 kg; bupropion −0.84 kg versus −3.46 kg). Only the bupropion cohort was significantly heavier at end-of-study versus the non-antidepressant cohort (108 kg versus 103 kg, P = 0.018). Conclusion and Relevance: Antidepressants may diminish the weight loss effect of GLP-1 RAs. Additional research is needed to assess whether all GLP-1 RAs are affected similarly and the optimal weight loss strategies in patients receiving antidiabetic therapy with comorbid depression.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 85%

Effect of Antidepressants on Glucagon-Like Peptide-1 Receptor Agonist-Related Weight Loss

Durell

Franks

Coon

et al. 2022

Journal of Pharmacy Technology

Self Cite

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show abstract

“…The weight loss observed here was greater than weight loss observed in trials of oral semaglutide for type 2 diabetes (−3.7 to −4.3 kg). 8 However, patients with, versus without, diabetes typically lose less weight in trials, a trend also seen in trials of high-dose liraglutide, high-dose injectable semaglutide, and orlistat. 8 Importantly, oral semaglutide is effectively a lower dose versus high-dose injectable semaglutide based on population pharmacokinetics reported in package inserts for oral semaglutide and standard-dose injectable semaglutide.…”

mentioning

confidence: 96%

“…8 However, patients with, versus without, diabetes typically lose less weight in trials, a trend also seen in trials of high-dose liraglutide, high-dose injectable semaglutide, and orlistat. 8 Importantly, oral semaglutide is effectively a lower dose versus high-dose injectable semaglutide based on population pharmacokinetics reported in package inserts for oral semaglutide and standard-dose injectable semaglutide. Therefore, we would not expect oral semaglutide to produce similar weight loss versus high-dose injectable semaglutide.…”

mentioning

confidence: 96%

“…[5][6][7] However, high-dose semaglutide's impact may be limited by cost and scant insurance coverage for "weight loss" medications. Updike et al 8 suggested using GLP1-RAs off-label for weight loss, at lower GLP1-RA doses approved for type 2 diabetes, in patients without diabetes, to increase patient access. With data supporting high-dose injectable semaglutide in patients without diabetes, oral semaglutide may be reasonable.…”

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confidence: 99%

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