Exenatide Adjunct to Nicotine Patch Facilitates Smoking Cessation and May Reduce Post-Cessation Weight Gain: a Pilot Randomized Controlled Trial

2021 ◽  
Author(s):  
Luba Yammine ◽  
Charles E Green ◽  
Thomas R Kosten ◽  
Constanza de Dios ◽  
Robert Suchting ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Body Weight ◽  
Weight Gain ◽  
Extended Release ◽  
Nicotine Patch ◽  
Withdrawal Symptoms ◽  
Secondary Outcome ◽  
Smoking Abstinence ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Introduction Approved pharmacological treatments for smoking cessation are modestly effective, underscoring the need for improved pharmacotherapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate the rewarding effects of nicotine in preclinical studies. We examined the efficacy of extended-release exenatide, a GLP-1R agonist, combined with nicotine replacement therapy (NRT, patch) for smoking cessation, craving and withdrawal symptoms, with post-cessation body weight as secondary outcome. Methods Eighty-four prediabetic and/or overweight smokers were randomized (1:1) to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received NRT (21 mg) and brief smoking cessation counseling. Seven-day point prevalence abstinence (expired CO level ≤5 ppm), craving, withdrawal and post-cessation body weight were assessed following 6 weeks of treatment. A Bayesian approach for analyzing generalized linear models yielded posterior probabilities (PP) to quantify the evidence favoring hypothesized effects of treatment on the study outcomes. Results Exenatide increased the risk for smoking abstinence compared to placebo (46.3% and 26.8%, respectively), (RR = 1.70; 95% credible interval = [0.96, 3.27]; PP = 96.5%). Exenatide reduced end-of-treatment craving in the overall sample and withdrawal among abstainers. Post-cessation body weight was 5.6 pounds lower in the exenatide group compared to placebo (PP=97.4%). Adverse events were reported in 9.5% and 2.3% of participants in the exenatide and placebo groups, respectively. Conclusions Exenatide, in combination with the NRT improved smoking abstinence, reduced craving and withdrawal symptoms, and decreased weight gain among abstainers. Findings suggest that the GLP-1R agonist strategy is worthy of further research in larger, longer duration studies. Implications Despite considerable progress in tobacco control, cigarette smoking remains the leading cause of preventable disease, disability, and death. In this pilot study, we showed that extended-release exenatide, a glucagon-like peptide-1 receptor agonist, added to the nicotine patch, improved abstinence and mitigated post-cessation body weight gain compared to patch alone. Further research is needed to confirm these initial positive results.

Glucagon-like peptid-1 in obese and diabetic patients after bariatric interventions

2021 ◽  
Vol 23 (1) ◽  
pp. 89-94
Author(s):  
Anna R. Volkova ◽  
Galina V. Semikova ◽  
Valentina S. Mozgunova ◽  
Margarita N. Maltseva ◽  
Vladimir L. Bondarenko ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Body Weight ◽  
Weight Gain ◽  
Diabetic Patients ◽  
Obese Patients ◽  
Weight Retention ◽  
Plateau Phase ◽  
The Third ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The relationship between the level of glucagon-like peptide-1 and repeated weight gain was evaluated in 31 patients suffering from grade IIIII obesity and type 2 diabetes mellitus after bariatric interventions for 3 years. It was found that the level of stimulated glucagon-like peptide-1 significantly increased by the third day after sleeve gastroplasty and gastroschunt compared to the initial parameters (p = 0.001 for obese patients; p = 0.000 for obese patients and diabetes mellitus). In the plateau phase (body weight retention) after bariatric intervention, the level of stimulated glucagon-like peptide-1 in obese patients and patients suffering from obesity in combination with diabetes mellitus did not significantly differ from the indicators of healthy individuals. There was no association between the level of glucagon-like peptide-1 and repeated weight gain. This may be due to the limited contribution of glucagon-like peptide-1 to body weight dynamics after bariatric interventions and the predominance of patient compliance. Thus, the level of stimulated glucagon-like peptide-1 at baseline, on the third day and in the plateau phase after bariatric intervention was not associated with the value of repeated weight gain.

scholarly journals Combination Lorcaserin and Nicotine Patch for Smoking Cessation Without Weight Gain

2019 ◽  
Vol 22 (9) ◽  
pp. 1627-1631 ◽  
Author(s):  
Jed E Rose ◽  
James M Davis
Keyword(s):  
Smoking Cessation ◽  
Weight Gain ◽  
Weight Change ◽  
Nicotine Patch ◽  
Strong Association ◽  
Smoking Abstinence ◽  
Clinical Trial Registration ◽  
Smoking Cessation Treatment ◽  
Quit Smoking ◽  
The Impact

Abstract Introduction This study explored the efficacy of combination lorcaserin and nicotine patch for smoking cessation treatment and prevention of postsmoking cessation weight gain. Methods We conducted a trial in which 61 adult daily smokers were asked to quit smoking using a combination of lorcaserin and nicotine patch. During the first 2 weeks of treatment prior to the quit day, participants were randomized to receive either lorcaserin (10 mg twice daily) plus nicotine patch (21 mg) or placebo plus nicotine patch (21 mg). Following this 2-week period, participants received both medications for 12 weeks. Outcomes included 4-week continuous smoking abstinence at the end of treatment (weeks 7–10 postquit attempt), weight change, ad libitum smoking, withdrawal symptoms, and ratings of cigarette reward. Results Biochemically confirmed continuous smoking abstinence from 7 to 10 weeks postquit attempt was 31.1% (90% confidence interval, 21.4%–40.8%). Participants who quit smoking showed no weight gain; in fact, mean weight change was minus 0.16 kg (SD = 3.27) over the study period. There was an unexpected but strong association (p = .006) between a decrease in sensory enjoyment of smoking and successful quit outcome on this regimen. During the prequit randomization period, lorcaserin versus placebo reduced the impact of smoking to relieve craving for cigarettes as well as the sensory enjoyment of smoking (p = .005). Adherence and tolerability to lorcaserin and nicotine patch was good. Conclusions The combination of lorcaserin and nicotine patch was well tolerated, associated with a relatively high smoking abstinence rate, and effectively prevented weight gain associated with quitting smoking. Implications This report provides an important contribution to the literature because it details evidence of a medication combination—lorcaserin and nicotine—that is effective for smoking cessation and for ameliorating weight gain associated with smoking cessation. For many smokers, postcessation weight gain is a major obstacle to quitting, and this medication combination provides a suitable treatment option for these smokers. Clinical Trial Registration NCT02906644

scholarly journals Once-weekly administration of dulaglutide, a glucagon-like peptide-1 receptor agonist, as monotherapy and combination therapy: review of the AWARD studies

2017 ◽  
Vol 20 (3) ◽  
pp. 220-230 ◽  
Author(s):  
Marina V. Shestakova ◽  
Ekaterina A. Yudovich
Keyword(s):  
Body Weight ◽  
Glycemic Control ◽  
Adverse Events ◽  
Receptor Agonist ◽  
Plasma Concentrations ◽  
Secondary Outcome ◽  
Treatment Needs ◽  
Weekly Administration ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

For the purpose of exploring the development, pharmacology and clinical trial program related to dulaglutide, we conducted a nonsystematic review of dulaglutide, focusing on the AWARD (Assessment of Weekly Administration of LY2189265 [dulaglutide] in Diabetes Assessment) program of randomized, phase 3 studies. Dulaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist that causes a variety of antidiabetogenic actions by acting on the incretin system. Steady-state plasma concentrations of dulaglutide are achieved between 2 and 4 weeks following a once-weekly administration. The AWARD 16 studies were conducted in patients with different treatment needs, ranging from patients with mild diabetes who can be treated with diet management and exercise to patients for whom target glycemic control cannot be achieved with conventional insulin treatment. Changes in HbA1c from baseline to the primary endpoint assessment (primary efficacy outcome) with dulaglutide were generally dose-dependent and significantly greater than those of active comparators and placebos (AWARD 15) or non-inferior to the comparators (AWARD 6). The results of secondary outcome measures demonstrated that glycemic control attained with dulaglutide was sustained for long-term and that a greater proportion of patients treated with dulaglutide achieved a target HbA1c level of 7.0% compared with placebo and/or active comparators. Reduction in fasting serum glucose, glucagon levels and body weight after dulaglutide treatment were noted in most AWARD studies. Although treatment-emergent adverse events were common with dulaglutide, the incidence was similar to that of active comparators in most AWARD studies, and serious adverse events were generally infrequent, except in patients with more severe disease or with prolonged therapy. Hypoglycemic and immunogenic events were also infrequent. In patients with type 2 diabetes, dulaglutide improves glycemic control and leads to clinically useful reduction in body weight in a range of treatment settings.

scholarly journals Chronic glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism desensitizes adipocyte GIPR activity mimicking functional GIPR antagonism

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Elizabeth A. Killion ◽  
Michelle Chen ◽  
James R. Falsey ◽  
Glenn Sivits ◽  
Todd Hager ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Preclinical Models ◽  
Prevent Weight Gain ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Antagonism or agonism of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) prevents weight gain and leads to dramatic weight loss in combination with glucagon-like peptide-1 receptor agonists in preclinical models. Based on the genetic evidence supporting GIPR antagonism, we previously developed a mouse anti-murine GIPR antibody (muGIPR-Ab) that protected diet-induced obese (DIO) mice against body weight gain and improved multiple metabolic parameters. This work reconciles the similar preclinical body weight effects of GIPR antagonists and agonists in vivo, and here we show that chronic GIPR agonism desensitizes GIPR activity in primary adipocytes, both differentiated in vitro and adipose tissue in vivo, and functions like a GIPR antagonist. Additionally, GIPR activity in adipocytes is partially responsible for muGIPR-Ab to prevent weight gain in DIO mice, demonstrating a role of adipocyte GIPR in the regulation of adiposity in vivo.

scholarly journals No Change in Serum Incretins Levels but Rise of Leptin Levels After Smoking Cessation: a Pilot Study

2016 ◽  
pp. 651-659 ◽  
Author(s):  
A. PANKOVA ◽  
E. KRALIKOVA ◽  
P. KAVALKOVA ◽  
L. STEPANKOVA ◽  
K. ZVOLSKA ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Body Weight ◽  
Peptide Yy ◽  
Gastric Inhibitory Polypeptide ◽  
Male Adult ◽  
Liquid Meal ◽  
Quit Smoking ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Obese Male

The mechanisms behind the changes of body weight after smoking cessation are only partially understood. To this end, we explored the possible effects of smoking cessation on incretin hormones, leptin and selected anthropometric, biochemical and other hormonal parameters. Twenty-two non-obese male adult smokers attending an ambulatory smoking cessation program in Prague, Czech Republic, were examined at the baseline. Thirteen patients (mean age 37.92±2.66 years, mean body mass index 25.56±0.69 kg/m2) successfully quit smoking and were examined three months after smoking cessation; relapsed smokers were not followed up. The patients underwent 2-h liquid meal test with Fresubin and repeated blood sampling for measurements of blood glucose, gastric inhibitory polypeptide (GIP), glucagon-like peptide 1 (GLP-1), amylin, insulin, leptin, peptide-YY (PYY) and pancreatic polypeptide (PP). Three months after smoking cessation, body weight increased (4.35±3.32 kg, p<0.001). Leptin levels increased significantly in all repeated samples, while levels of GIP, GLP-1, amylin, insulin, PYY and PP remained unchanged. In conclusions, smoking cessation increased leptin levels probably owing to weight gain while it did not influence incretin levels.

Efficacy and tolerability of pharmacological interventions on metabolic disturbance induced by atypical antipsychotics in adults: A systematic review and network meta-analysis

2021 ◽  
pp. 026988112110353
Author(s):  
Yewei Wang ◽  
Dandan Wang ◽  
Jie Cheng ◽  
Xinyu Fang ◽  
Yan Chen ◽  
...  
Keyword(s):  
Body Weight ◽  
Atypical Antipsychotics ◽  
Randomized Clinical Trials ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Metabolic Disturbance ◽  
Pharmacological Interventions ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Meta Analyses

Background: There have been a few systematic reviews and conventional meta-analyses reporting effect of drugs on metabolic disturbance induced by atypical antipsychotics (AAPs). However, few of them provided sufficient and comprehensive comparisons between pharmacological interventions. Aims: We aimed to qualitatively compare drugs’ effect on AAPs-induced metabolic abnormalities by using network meta-analysis (NMA). Methods: We searched PubMed, EMBASE, Web of Science, Cochrane Controlled Register of Trials (CENTRAL), and PsycINFO on March 26, 2019. Of 5889 records identified, 61 randomized clinical trials including 3467 participants were included. We estimated weighted mean difference (WMD) and odds ratio (OR) using NMA. We assessed the risk of bias of individual studies with the Review Manager 5.3. Primary outcomes included change of body weight and body mass index (BMI). Secondary outcomes included change of other cardiometabolic risk factors, acceptability, and tolerability. Results: For body weight, topiramate (WMD −5.4, 95% CI −7.12 to −3.68), zonisamide (−3.44, 95% CI −6.57 to −0.36), metformin (−3.01, 95% CI −4.22 to −1.83), glucagon-like peptide-1 receptor agonists (GLP-1RAs) (−3.23, 95% CI −5.47 to −0.96), and nizatidine (−2.14, 95% CI −4.01 to −0.27) were significantly superior to placebo. Results regarding to BMI were similar to that of body weight. With respect to tolerability, only topiramate (OR 24, 95% CI 3.15 to 648) was inferior to placebo. Conclusions: Considering both efficacy and tolerability, evidence from this NMA indicates zonisamide, metformin, GLP-1RAs, and nizatidine in adults should be the first-line treatment for alleviating AAPs-induced weight gain or elevated BMI.

scholarly journals How glucagon-like peptide 1 receptor agonists work

2021 ◽  
Author(s):  
Christine Rode Andreasen ◽  
Andreas Andersen ◽  
Filip Krag Knop ◽  
Tina Vilsbøll
Keyword(s):  
Body Weight ◽  
Therapeutic Potential ◽  
Clinical Effects ◽  
Glucose Lowering ◽  
Receptor Agonists ◽  
Reduce Body Weight ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Clinical Utilisation

Recent years, glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become central in the treatment of type 2 diabetes (T2D). In addition to their glucose-lowering properties with low risk of hypoglycaemia, GLP-1RAs reduce body weight and show promising results in reducing cardiovascular risk and renal complications in high-risk individuals with T2D. These findings have changed guidelines on T2D management over the last years, and GLP-1RAs are now widely used in overweight patients with T2D as well as in patients with T2D and cardiovascular disease regardless of glycaemic control. The currently available GLP-1RAs have different pharmacokinetic profiles and differ in their ability to improve glycaemia, reduce body weight and in their cardio- and renal protective potentials. Understanding how these agents work, including insights into their pleiotropic effects on T2D pathophysiology, may improve their clinical utilisation and be useful for exploring other indications such as non-alcoholic steatohepatitis and neurodegenerative disorders. In this review, we provide an overview of approved GLP-1RAs, their clinical effects and mode of actions, and we offer insights into the potential of GLP-1RAs for other indications than T2D. Finally, we will discuss the emerging data and therapeutic potential of using GLP-1RAs in combinations with other receptor agonists.

scholarly journals The experience with the clinical application of liralgutide (victosa), the first analog of human glucagon-like peptide-1 in the patients with type 2 diabetes mellitus - expanding the range of possibilities

2012 ◽  
Vol 58 (3) ◽  
pp. 51-55
Author(s):  
E N Ostroukhova ◽  
O K Khmel'nitskiĭ ◽  
E I Krasil'nikova ◽  
K S Davidenko
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Adverse Reactions ◽  
Brand Name ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

This paper reports the results of the treatment of 71 patients presenting with type 2 diabetes mellitus using liraglutide, a long-acting analog of glucagon-like peptide-1 (GLP-1) marketed under the brand name Victoza. Practically all the patients experienced either improvement or normalization of the parameters of carbohydrate metabolism in conjunction with a reduction of their body weight and arterial pressure. There were no severe hypoglycemic episodes and other adverse reactions to the therapy. It is recommended that Victoza should be more widely used for the treatment of the patients with type 2 diabetes mellitus.

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