Dataset Information

Varenicline and Lorcaserin for Smoking Cessation and Weight Gain Prevention: A Randomized Clinical Trial.

ABSTRACT:

Objective

To evaluate the safety and effectiveness of combination varenicline with lorcaserin in preventing post-cessation weight gain.

Participants and methods

We conducted a randomized (varenicline for 12 weeks + lorcaserin for 24 weeks vs varenicline for 12 weeks + placebo for 24 weeks) phase II clinical study to obtain preliminary data on the safety and effectiveness of combination varenicline and lorcaserin in preventing post-cessation weight gain in overweight and obese smokers. Eighty-four overweight and obese (body mass index [BMI], 27-40 kg/m²) cigarette smokers were randomized before study termination (lorcaserin: n=40; placebo: n=44). The primary outcomes were weight and waist circumference (WC) changes at 12 and 24 weeks in smokers meeting criteria for prolonged smoking abstinence.

Results

Thirty-nine participants met criteria for prolonged smoking abstinence at 12 weeks (46%) and 21 at 24 weeks (25%). No significant treatment effect was observed at 12 weeks with lorcaserin compared with placebo (weight difference, -0.7 kg; 90% CI, -2.6 to 1.1 kg; P=.51; WC difference, -1.9 cm; 90% CI, -4.2 to 0.5 cm; P=.18; or BMI difference, -0.4 kg/m²; 90% CI, -1.1 to 0.3 kg/m²; P=.33). No significant treatment effect was observed between lorcaserin at 24 weeks compared with placebo (weight, 1.4 kg; 90% CI, -3.8 to 6.7 kg; P=.65; WC, -0.9 cm; 90% CI, -5.8 to 4.0 cm; P=.75; or BMI 0.29 kg/m²; 90% CI, -1.5 to 2.12 kg/m²; P=.79).

Conclusion

Weight gain and WC increases after prolonged smoking abstinence were not reduced using combination varenicline and lorcaserin. The results do not support further research in the obese and weight-concerned smoking population using lorcaserin or similar drugs.

Trial registration

clinicaltrials.gov Identifier: NCT02412631.

SUBMITTER: Hurt RT

PROVIDER: S-EPMC9500518 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Varenicline and Lorcaserin for Smoking Cessation and Weight Gain Prevention: A Randomized Clinical Trial.

Hurt Ryan T RT Croghan Ivana T IT Schroeder Darrell R DR Choi Doo-Sup DS Fischer Karen K Fokken Shawn S Ebbert Jon O JO

Mayo Clinic proceedings. Innovations, quality & outcomes 20220921 5

<h4>Objective</h4>To evaluate the safety and effectiveness of combination varenicline with lorcaserin in preventing post-cessation weight gain.<h4>Participants and methods</h4>We conducted a randomized (varenicline for 12 weeks + lorcaserin for 24 weeks vs varenicline for 12 weeks + placebo for 24 weeks) phase II clinical study to obtain preliminary data on the safety and effectiveness of combination varenicline and lorcaserin in preventing post-cessation weight gain in overweight and obese smok ...[more]

PMID: 36160639

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Project description:ImportanceSome cigarette smokers may not be ready to quit immediately but may be willing to reduce cigarette consumption with the goal of quitting.ObjectiveTo determine the efficacy and safety of varenicline for increasing smoking abstinence rates through smoking reduction.Design, setting, and participantsRandomized, double-blind, placebo-controlled, multinational clinical trial with a 24-week treatment period and 28-week follow-up conducted between July 2011 and July 2013 at 61 centers in 10 countries. The 1510 participants were cigarette smokers who were not willing or able to quit smoking within the next month but willing to reduce smoking and make a quit attempt within the next 3 months. Participants were recruited through advertising.InterventionsTwenty-four weeks of varenicline titrated to 1 mg twice daily or placebo with a reduction target of 50% or more in number of cigarettes smoked by 4 weeks, 75% or more by 8 weeks, and a quit attempt by 12 weeks.Main outcomes and measuresPrimary efficacy end point was carbon monoxide-confirmed self-reported abstinence during weeks 15 through 24. Secondary outcomes were carbon monoxide-confirmed self-reported abstinence for weeks 21 through 24 and weeks 21 through 52.ResultsThe varenicline group (n = 760) had significantly higher continuous abstinence rates during weeks 15 through 24 vs the placebo group (n = 750) (32.1% for the varenicline group vs 6.9% for the placebo group; risk difference (RD), 25.2% [95% CI, 21.4%-29.0%]; relative risk (RR), 4.6 [95% CI, 3.5-6.1]). The varenicline group had significantly higher continuous abstinence rates vs the placebo group during weeks 21 through 24 (37.8% for the varenicline group vs 12.5% for the placebo group; RD, 25.2% [95% CI, 21.1%-29.4%]; RR, 3.0 [95% CI, 2.4-3.7]) and weeks 21 through 52 (27.0% for the varenicline group vs 9.9% for the placebo group; RD, 17.1% [95% CI, 13.3%-20.9%]; RR, 2.7 [95% CI, 2.1-3.5]). Serious adverse events occurred in 3.7% of the varenicline group and 2.2% of the placebo group (P = .07).Conclusions and relevanceAmong cigarette smokers not willing or able to quit within the next month but willing to reduce cigarette consumption and make a quit attempt at 3 months, use of varenicline for 24 weeks compared with placebo significantly increased smoking cessation rates at the end of treatment, and also at 1 year. Varenicline offers a treatment option for smokers whose needs are not addressed by clinical guidelines recommending abrupt smoking cessation.Trial registrationclinicaltrials.gov Identifier: NCT01370356.

Project description:ImportanceCytisine is more effective than placebo and nicotine replacement therapy for smoking cessation. However, cytisine has not been tested against the most effective smoking cessation medication, varenicline, which is associated with adverse events known to lead to discontinuation of therapy.ObjectiveTo examine whether standard cytisine treatment (25 days) was at least as effective as standard varenicline treatment (84 days) for smoking cessation.Design, setting, and participantsThis noninferiority, open-label randomized clinical trial with allocation concealment and blinded outcome assessment was undertaken in Australia from November 2017 through May 2019; follow-up was completed in January 2020. A total of 1452 Australian adult daily smokers willing to make a quit attempt were included. Data collection was conducted primarily by computer-assisted telephone interview, but there was an in-person visit to validate the primary outcome.InterventionsTreatments were provided in accordance with the manufacturers' recommended dosage: cytisine (n = 725), 1.5-mg capsules taken 6 times daily initially then gradually reduced over the 25-day course; varenicline (n = 727), 0.5-mg tablets titrated to 1 mg twice daily for 84 days (12 weeks). All participants were offered referral to standard telephone behavioral support.Main outcomes and measuresThe primary outcome was 6-month continuous abstinence verified using a carbon monoxide breath test at 7-month follow-up. The noninferiority margin was set at 5% and the 1-sided significance threshold was set at .025.ResultsAmong 1452 participants who were randomized (mean [SD] age, 42.9 [12.7] years; 742 [51.1%] women), 1108 (76.3%) completed the trial. Verified 6-month continuous abstinence rates were 11.7% for the cytisine group and 13.3% for the varenicline group (risk difference, -1.62% [1-sided 97.5% CI, -5.02% to ∞]; P = .03 for noninferiority). Self-reported adverse events occurred less frequently in the cytisine group (997 events among 482 participants) compared with the varenicline group (1206 events among 510 participants) and the incident rate ratio was 0.88 (95% CI, 0.81 to 0.95; P = .002).Conclusions and relevanceAmong daily smokers willing to quit, cytisine treatment for 25 days, compared with varenicline treatment for 84 days, failed to demonstrate noninferiority regarding smoking cessation.Trial registrationanzctr.org.au Identifier: ACTRN12616001654448.

Project description:ImportanceCigarette smoking is the leading cause of preventable morbidity and mortality in the United States and worldwide, and most tobacco users begin smoking in adolescence. Although advances have yielded efficacious pharmacotherapies to complement smoking cessation counseling in adults, far less progress has been made in addressing tobacco use in adolescence.ObjectiveTo evaluate the efficacy and safety of varenicline tartrate for smoking cessation in adolescents and young adults.Design, setting, and participantsThis 2-group randomized, placebo-controlled, double-blind intention-to-treat clinical trial enrolled a volunteer sample of treatment-seeking adolescent and young adult cigarette smokers (n = 157) aged 14 to 21 years at an outpatient clinical site in Charleston, South Carolina, from August 15, 2012, to October 20, 2017. Follow-up was completed on January 25, 2018. Data were analyzed from March 19, 2018, to August 11, 2018, with further revisions completed April 10, 2019.InterventionsParticipants were randomized in a 1:1 ratio to a 12-week course of varenicline (n = 77) or placebo (n = 80). All participants received weekly smoking cessation counseling.Main outcomes and measuresThe preselected primary efficacy outcome was urine cotinine level-confirmed 7-day abstinence at the end of treatment. Secondary efficacy outcomes included weekly abstinence throughout active treatment, abstinence at posttreatment follow-up visits, and time to first 7-day abstinence. The primary safety outcome was the frequency of treatment-emergent adverse events.ResultsA total of 157 participants were enrolled (94 male [59.9%]; mean [SD] age, 19.1 [1.5] years). The varenicline and placebo groups did not differ in the primary outcome of cotinine-confirmed self-reported 7-day abstinence at the end of treatment (varenicline group, 4 of 45 [8.9%]; placebo group, 4 of 45 [8.9%]; risk ratio [RR], 0.97; 95% CI, 0.29-2.99; P = .96). However, among secondary outcomes, the varenicline group achieved self-reported earlier abstinence of at least 7 days (hazard ratio, 1.91; 95% CI, 1.12-3.27) and demonstrated higher rates of self-reported weekly abstinence during the full course of treatment (RR, 1.81; 95% CI, 1.09-2.99; P = .02) and at posttreatment follow-up (RR, 1.82; 95% CI, 1.01-3.28; P = .02). Study medication was generally well tolerated, and treatment-emergent adverse events did not differ between groups (any adverse events, 55 [71.4%] in the varenicline group vs 60 [75.0%] in the placebo group; RR, 0.95; 95% CI, 0.79-1.15; P = .61).Conclusions and relevanceWhen added to weekly cessation counseling for adolescent cigarette smokers, varenicline, compared with placebo, was well tolerated but did not improve end-of-treatment abstinence. However, varenicline may hasten abstinence and yield improvements in posttreatment abstinence outcomes.Trial registrationClinicalTrials.gov identifier: NCT01509547.

Project description:IntroductionPost-cessation weight gain (PCWG) is a major barrier to maintaining abstinence, especially in weight-concerned smokers. Varenicline is the most effective medication for smoking cessation but has minimal impact on PCWG. Lorcaserin is an FDA-approved medication for weight management in overweight or obese patients which also provides a noticeable benefit in treating drug dependence. We hypothesized that combining varenicline with lorcaserin may help prevent PCWG. We conducted an open-label, single arm, Phase II clinical pilot study to obtain preliminary data on the safety and effectiveness of combination varenicline and lorcaserin in preventing PCWG in overweight and obese smokers.MethodsTwenty overweight or obese (body mass index 27-40 kg/m2) cigarette smokers were enrolled. The primary outcomes were weight and waist circumference (WC) changes at 12 and 26 weeks in smokers meeting criteria for prolonged smoking abstinence. All participants received open-label varenicline (1 mg twice a day) and lorcaserin (10 mg twice a day) for 12 weeks with follow-up at 26 weeks.ResultsTen subjects met criteria for prolonged smoking abstinence at 12 weeks (50%) and 6 at 26 weeks (30%). Among those achieving prolonged smoking abstinence at 12 weeks, WC was +0.2 ± 6.0 cm (90% CI; -2.9, +3.4) and weight gain was +1.1 ± 3.9 kg (90% CI; -0.9, +3.1).ConclusionsWeight gain and WC increases following prolonged smoking abstinence may be reduced among overweight and obese smokers using combination varenicline and lorcaserin. This combinatory treatment warrants further research in the obese and weight-concerned smoking population.ImplicationsThis is the first published prospective pilot study to evaluate lorcaserin for use in reducing PCWG in overweight and obese smokers. When combined with varenicline, lorcaserin minimized PCWG and increases in WC. In addition to the benefit on PCWG reduction, lorcaserin may be a potential new pharmacological treatment for smoking cessation and warrants further larger studies.

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Dataset Information

Varenicline and Lorcaserin for Smoking Cessation and Weight Gain Prevention: A Randomized Clinical Trial.

Objective

Participants and methods

Results

Conclusion

Trial registration

Publications

Varenicline and Lorcaserin for Smoking Cessation and Weight Gain Prevention: A Randomized Clinical Trial.

Similar Datasets

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