Dataset Information

Metformin reduces 12-month change in body weight among people newly commenced on clozapine: a retrospective naturalistic cohort study.

ABSTRACT:

Background

People with schizophrenia have a 15-20-year reduction in life expectancy, driven in part by the metabolic effects of antipsychotics. Clozapine is associated with the highest rates of weight gain. As clozapine remains the most effective antipsychotic for treatment-resistant schizophrenia (TRS), identifying treatments to ameliorate clozapine-induced weight gain (CIWG) is urgently needed to reduce this morality gap.

Methods

We retrospectively analysed digital health records of patients with TRS aged 18-65 newly initiated on clozapine at four tertiary hospitals in south-east Queensland from 1 March 2017 to 30 June 2019. Our primary outcome was the effect of metformin on change in percentage bodyweight at 12 months after clozapine initiation, with secondary outcome being proportion with >5% or >7% bodyweight change. We also explored impact on bodyweight change of other variables including sex, tobacco smoking, type 2 diabetes (T2DM), age, clozapine level and dose and clozapine/norclozapine ratio.

Results

Among 90 patients initiated on clozapine, metformin use (n = 48) was associated with a smaller increase in percentage bodyweight (1.32% versus 5.95%, p = 0.031), lower rates of >7% gain in bodyweight (37.8% versus 63.0%, p = 0.025) but not >5% gain in bodyweight. Age below the median (32.0 years) was associated with greater bodyweight gain (5.55% versus 1.22%, p = 0.046). Sex, tobacco smoking, T2DM, clozapine dose and level and clozapine/norclozapine ratio were not associated with differences in change in bodyweight.

Conclusion

In this small retrospective cohort study, use of metformin within 12-months of clozapine initiation was associated with a statistically and clinically significant reduction in CIWG. Although there is increasing evidence for the role of metformin to ameliorate bodyweight gain at time of clozapine initiation, our findings need replication and testing in a randomised controlled trial before recommending metformin co-commencement with clozapine as standard clinical practice.

SUBMITTER: Spokes J

PROVIDER: S-EPMC7970229 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundPrior research on the relationship between sleep and attempted weight loss failed to recognize the multidimensional nature of sleep. We examined the relationship between a composite measure of sleep health and change in weight and body composition among adults in a weight loss intervention.MethodsAdults (N = 125) with overweight or obesity (50.3 ± 10.6 years, 91% female, 81% white) participated in a 12-month behavioral weight loss intervention, with assessments of sleep, weight, fat mass, and fat-free mass at baseline, 6 months, and 12 months. Six sleep dimensions (regularity, satisfaction, alertness, timing, efficiency, and duration) were categorized as "good" or "poor" using questionnaires and actigraphy. A composite score was calculated by summing the number of "good" dimensions. Obstructive sleep apnea (OSA) was assessed in a subsample (n = 117), using the apnea-hypopnea index (AHI) to determine OSA severity. Linear mixed modeling was used to examine the relationships between sleep health and outcomes of percent weight, fat mass, or fat-free mass change during the subsequent 6-month interval, adjusting for age, sex, bed partner, and race; an additional model adjusted for AHI.ResultsMean baseline and 6-month sleep health was 4.5 ± 1.1 and 4.5 ± 1.2, respectively. Mean weight, fat mass, and fat-free mass changes from 0 to 6 months were -9.3 ± 6.1%, -16.9 ± 13.5%, and -3.4 ± 3.4%, respectively, and 0.4 ± 4.8%, -0.3 ± 10.3%, and 0.7 ± 4.1% from 6 to 12 months. Better sleep health was associated with greater subsequent weight loss (P = 0.016) and fat loss (P = 0.006), but not fat-free mass loss (P = 0.232). Following AHI adjustment, the association between sleep health and weight loss was attenuated (P = 0.102) but remained significant with fat loss (P = 0.040). Regularity, satisfaction, timing, and efficiency were each associated with weight and/or fat loss (P ≤ 0.041).ConclusionsBetter sleep health was associated with greater weight and fat loss, with associations attenuated after accounting for OSA severity. Future studies should explore whether improving sleep health, OSA, or the combination improves weight loss.

Project description:BACKGROUND/OBJECTIVES:Despite the effectiveness of bariatric surgery, there is still substantial variability in long-term weight outcomes and few factors with predictive power to explain this variability. Neuroimaging may provide a novel biomarker with utility beyond other commonly used variables in bariatric surgery trials to improve prediction of long-term weight-loss outcomes. The purpose of this study was to evaluate the effects of sleeve gastrectomy (SG) on reward and cognitive control circuitry postsurgery and determine the extent to which baseline brain activity predicts weight loss at 12-month postsurgery. SUBJECTS/METHODS:Using a longitudinal design, behavioral, hormone and neuroimaging data (during a desire for palatable food regulation paradigm) were collected from 18 patients undergoing SG at baseline (<1 month prior) and 12-month post-SG. RESULTS:SG patients lost an average of 29.0% of their weight (percentage of total weight loss (%TWL)) at 12-month post-SG, with significant variability (range: 16.0-43.5%). Maladaptive eating behaviors (uncontrolled, emotional and externally cued eating) improved (P<0.01), in parallel with reductions in fasting hormones (acyl ghrelin, leptin, glucose, insulin; P<0.05). Brain activity in the nucleus accumbens (NAcc), caudate, pallidum and amygdala during desire for palatable food enhancement vs regulation decreased from baseline to 12 months (P (family-wise error (FWE))<0.05). Dorsolateral and dorsomedial prefrontal cortex activity during desire for palatable food regulation (vs enhancement) increased from baseline to 12 months (P(FWE)<0.05). Baseline activity in the NAcc and hypothalamus during desire for palatable food enhancement was significantly predictive of %TWL at 12 months (P (FWE)<0.05), superior to behavioral and hormone predictors, which did not significantly predict %TWL (P>0.10). Using stepwise linear regression, left NAcc activity accounted for 54% of the explained variance in %TWL at 12 months. CONCLUSIONS:Consistent with previous obesity studies, reward-related neural circuit activity may serve as an objective, relatively robust predictor of postsurgery weight loss. Replication in larger studies is necessary to determine true effect sizes for outcome prediction.

Project description:Background:Reductions in energy intake are seen in weight loss trials, but whether this occurs with improvements to diet quality (DQ) is less established. The aim of this study was to evaluate changes in diet quality in a sample of volunteers in a weight loss trial. Methods:This was a secondary analysis of dietary data from a lifestyle intervention trial (the HealthTrack study) which advised on dietary guidelines. The trial ran for 12 months with three treatment groups: control (general advice C), intervention (individualised advice, I), and intervention plus a supplement of walnuts (IW). Both the published a priori diet quality score (APDQS, maximum score 164) and a study specific Diet Quality Tracker (DQT, maximum score 44) indicated compliance to dietary advice. DQ scores calculated at 0, 3months and 12months were evaluated using two-way RMANOVA, one-way ANOVA and one-way RMANOVA. Changes in intakes of food groups and nutrients were analysed using Kruskal-Wallis and Friedman's tests. Results:There were no differences between groups at baseline, but at 3months IW recorded higher DQ scores (APDQS:96?±?10; DQT:22?±?5, P?<?1?×?10-3 for both) compared to I (APDQS:91?±?13, P?<?1?×?10-3; DQT:21?±?4, P?<?1?×?10-2) and C (APDQS:87?±?12, P?<?5?×?10-2; DQT:19?±?4, P?>?5?×?10-2), and a higher consumption of nuts at 3 months (P?<?1?×?10-3), and 12months (P?<?1?×?10-2). All groups reported decreased intakes of discretionary foods/beverages assessed by the DQT (P?<?1?×?10-3 for IW and I; P?<?1?×?10-2 for C). The APDQS showed this as reduced intakes of grain based desserts (P?<?1?×?10-3 at 3 and 12months), and salty snacks at 12months (P?<?1?×?10-3 for IW and I; P?<?5?×?10-2 for C). Intakes of monounsaturated and saturated fatty acids were lowest, and polyunsaturated fatty acids highest for IW (P?<?1?×?10-3), resulting in a higher dietary polyunsaturated:saturated fat ratio (P?<?1?×?10-3). Conclusions:Lifestyle intervention addressing dietary guidelines can lead to significant reductions in consumption of discretionary foods and saturated fat, but individualised advice may have a greater impact on improving overall DQ regardless of DQI used. Providing a healthy food supplement may help assure higher DQ and where the food is walnuts, produce commensurate differences in dietary fatty acid profiles. Trial registration:ANZCTRN 12614000581662. Date of registration: 30th May 2014.