FEASIBILITY AND PRELIMINARY EFFICACY OF TIRZEPATIDE FOR INDIVIDUALS WITH MODERATE/SEVERE METHAMPHETAMINE USE DISORDER

Glucagon-like peptide-1 (GLP-1) agonists have gained recent attention for drug repurposing to treat substance use disorder. Yet, tirzepatide, a dual agonist of GLP1/glucose-dependent insulinotropic polypeptide, has not been studied systematically, especially for methamphetamine use disorder (MtUD).

Methods

This interim analysis included participants with moderate/severe MUD who received eight weeks of treatment with tirzepatide (2.5 mg/week for 4 weeks, then 5.0 mg/week for 4 weeks) for a weight-related indication (NCT06745128). Craving over the past week was assessed using Visual Analog Scale (VAS; 0=did not crave methamphetamine at all, 100=had the most intense craving possible). Current craving was assessed using 10-item Stimulant Craving Questionnaire (STCQ). Depression, anxiety, anhedonia, activity impairment and gastrointestinal symptoms were assessed weekly using Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR), 7-item Generalized Anxiety Disorder (GAD-7) scale, Snaith Hamilton Pleasure Scale (SHAPS), Work Productivity and Activity Impairment (WPAI) scale, and Gastrointestinal Symptom Rating Scale (GSRS), respectively.

Results

Of the 42 individuals screened, 35 were enrolled [20 females/15 males; mean (standard deviation, SD) age = 46.1 (8.3) years]. Two individuals dropped out after the first dose due to gastrointestinal side effects. Overall adherence to weekly injection visits was 95.0%. Mean (SD) of BMI, weight (in pounds), VAS, STCQ, QIDS-SR, GAD-7, SHAPS, WPAI activity impairment and GSRS at baseline were 35.9 (7.5), 224.8 (50.7), 57.0 (24.8), 41.6 (12.4), 8.2 (4.4), 8.7 (6.7), 2.4 (2.9), 29.4 (31.7), and 25.4 (11.2), respectively. After eight weeks of treatment with tirzepatide, there were significant reductions in BMI [estimate(β)= -2.3, standard error(SE)= 0.2, p < 0.001], weight (β= -14.5, SE= 1.0, p < 0.001), VAS (β= -20.4, SE= 5.2, p < 0.001), STCQ (β= -9.8, SE= 2.6, p < 0.001), QIDS-SR (β= -2.6, SE= 0.7, p < 0.001), GAD-7 (β= -3.5, SE= 1.0, p=0.001), and WPAI-activity impairment (β= -14.7, SE= 5.1, p=0.004) but no changes in SHAPS (p=0.72) and GSRS (p=0.98).

Conclusions

This study supports the feasibility of using tirzepatide for MUD and provides preliminary evidence for its efficacy in MUD by reducing craving for methamphetamine, depression, anxiety, and daily activity impairment.

References

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