Table 4 Descriptive characteristics of included preclinical and clinical studies
Author(s) | Participants | Intervention | Duration | Outcome(s) of interest |
|---|---|---|---|---|
Preclinical studies | ||||
Egecioglu et al. (2013) | NMRI mice (n = 8) per treatment combination (vehicle-vehicle, Ex4-vehicle, vehicle- nicotine or Ex4-nicotine) administered intraperitoneal nicotine | Ex-4 (2.4 μg/kg) administered intraperitoneally 10 min before nicotine administration | 8 days | Ex-4 administered into nucleus accumbens reduced reward induced by nicotine and food, and is important for attenuation of nicotine-induced activation of the mesolimbic dopamine system. Ex-4 was also reported to attenuate hyperphagia |
Tuesta et al. (2017) | Various groups including wild-type and Glp1r knockout mice administered nicotine. Numbers for each specific group varied (n = 10–12) | Sitagliptin (10 mg/kg) or Ex-4 (≤ 10 µg/kg) | Not stated | GLP-1RAs decreased nicotine intake. The IPN was shown to be important in nicotine avoidance by the MHb-IPN circuit, being a substrate for the inhibitory actions of GLP-1 on nicotine uptake |
Herman et al. (2023) | Male (n = 63) and female (n = 58) rats self-administered intravenous nicotine | Liraglutide (25 μg/kg, i.p.) daily | 21 days | Nicotine-induced withdrawal, hyperphagia, and body weight gain was prevented/ minimized in these rats with no malaise-like effects |
Falk et al. (2023) | Diet-induced male obese mice (n = 8) administered nicotine once daily | Liraglutide (10 nmol/kg) subcutaneously once daily | 16 days | Co-administration of nicotine and liraglutide synergistically lowered body weight. Significant reductions in food intake was also observed. Nicotine-induced dopamine release was attenuated by liraglutide, suggesting alterations in reward processing pathways |
Shankar et al. (2023) | Experiment 1: male (n = 10) and female (n = 10) rats Experiment 2: male (n = 6) and female (n = 6) rats Experiment 3: male (n = 6) and female (n = 6) rats. All rats were administered nicotine | 7-36amide (20 μg/kg) subcutaneously daily | Experiment 1: 14 days Experiment 2: 5–7 days Experiment 3: 5–7 days | Nicotine injection decreased circulating levels of GLP-1 and the drug’s potential to mitigate obesity may have a role in regulating the increased food intake observed in nicotine-dependent rats |
Clinical studies | ||||
Yammine et al. (2021) | 84 Prediabetic and/or overweight smokers were randomized to control (n = 42) or experimental (n = 42) | Extended-release exenatide (2 mg) subcutaneously once weekly adjunctively with a 21 mg nicotine patch and smoking cessation counseling | 6 weeks | Participants receiving exenatide reported reduced cravings and withdrawal symptoms compared to the placebo group. Exenatide adjunct therapy showed potential in reducing post-cessation weight gain. The primary outcome was the rate of smoking abstinence verified by expired carbon monoxide (CO) levels |
Lengsfeld et al. (2023) | 255 Participants were randomized to control (n = 128) or experimental (n = 127) | Dulaglutide (1.5 mg) subcutaneously once weekly adjunctive to standard of care smoking cessation therapy | 12 weeks | The biochemically confirmed 7-day point prevalence abstinence rate at 12 weeks was 27% in the dulaglutide group compared to 18% in the placebo group. The dulaglutide group also experienced less weight gain post-nicotine cessation as well as reduced cravings |
Luthi et al. (2024) | 255 participants were randomized to control (n = 128) or experimental (n = 127) | Dulaglutide (1.5 mg) subcutaneously once weekly adjunctive to standard of care smoking cessation therapy | 12 months | The point-prevalence abstinence rate at 52 weeks was 32% in the dulaglutide group and in the placebo group, showing no significant difference. The placebo group had an average weight gain of + 3.1 kg, while the dulaglutide group had an average weight gain of + 2.8 kg. Both groups experienced a decrease in nicotine cravings from baseline to week 12 |