Glucagon‐like peptide‐1 receptor agonists for antipsychotic‐associated cardio‐metabolic risk factors: A systematic review and individual participant data meta‐analysis

Siskind, Dan; Hahn, Margaret; Correll, Christoph U.; Fink-Jensen, Anders; Russell, Anthony; Bak, Nikolaj; Broberg, Brian Villumsen; Larsen, John; Ishøy, Pelle L.; Vilsbøll, Tina; Knop, Filip K.; Kisely, Steve; Ebdrup, Bjørn H

doi:10.1111/dom.13522

Cited by 87 publications

(67 citation statements)

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“…Amantadine was associated with higher rates of insomnia (RR=3.83, 95% CI: 1.41 to 10.38, p=0.008, NNH=9) and abdominal discomfort (quantitative data not provided). GLP‐1 RAs were associated with higher rates of nausea (NNH=3.8, 95% CI: 2.4 to 9.7, p<0.05). Among H2 antagonists, famotidine and ranitidine were not associated with higher rates of adverse reactions, while nizatidine had higher rates of dry mouth (RR=4.89, p=0.04; NNH=17, p=0.03) and depression (RR=5.00, p=0.03; NNH=17, p=0.02).…”

Section: Resultsmentioning

confidence: 98%

“…Of 3,709 search engine hits, 27 meta‐analyses were included, representing a total of 128 meta‐analyzed trials and 47,231 study participants.…”

Section: Resultsmentioning

confidence: 99%

“…There were meta‐analytic data for 17 different pharmacological interventions: aripiprazole augmentation, fluoxetine, metformin, nizatidine, NMDA receptor antagonists including amantadine and memantine, ranitidine, topiramate, dextroamphetamine, d‐fenfluramine, famotidine, metformin in combination with sibutramine, orlistat, rosiglitazone, fluvoxamine, glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), and switching from olanzapine to quetiapine or aripiprazole.…”

Section: Resultsmentioning

confidence: 99%

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The impact of pharmacological and non‐pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta‐review of meta‐analyses of randomized controlled trials

et al. 2019

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We summarized and compared meta-analyses of pharmacological and non-pharmacological interventions targeting physical health outcomes among people with schizophrenia spectrum disorders. Major databases were searched until June 1, 2018. Of 3,709 search engine hits, 27 metaanalyses were included, representing 128 meta-analyzed trials and 47,231 study participants. While meta-analyses were generally of adequate or high quality, meta-analyzed studies were less so. The most effective weight reduction interventions were individual lifestyle counseling (standardized mean difference, SMD=-0.98) and exercise interventions (SMD=-0.96), followed by psychoeducation (SMD=-0.77), aripiprazole augmentation (SMD=-0.73), topiramate (SMD=-0.72), d-fenfluramine (SMD=-0.54) and metformin . Regarding waist circumference reduction, aripiprazole augmentation (SMD=-1.10) and topiramate (SMD=-0.69) demonstrated the best evidence, followed by dietary interventions . Dietary interventions were the only to significantly improve (diastolic) blood pressure (SMD=-0.39). Switching from olanzapine to quetiapine or aripiprazole (SMD=-0.71) and metformin (SMD=-0.65) demonstrated best efficacy for reducing glucose levels, followed by glucagon-like peptide-1 receptor agonists (SMD=-0.39), dietary interventions (SMD=-0.37) and aripiprazole augmentation (SMD=-0.34), whereas insulin resistance improved the most with metformin (SMD=-0.75) and rosiglitazone . Topiramate had the greatest efficacy for triglycerides (SMD=-0.68) and low-density lipoprotein (LDL)-cholesterol (SMD=-0.80), whereas metformin had the greatest beneficial effects on total cholesterol (SMD=-0.51) and high-density lipoprotein (HDL)-cholesterol (SMD=0.45). Lifestyle interventions yielded small effects for triglycerides, total cholesterol and LDL-cholesterol (SMD=-0.35 to -0.37). Only exercise interventions increased exercise capacity (SMD=1.81). Despite frequent physical comorbidities and premature mortality mainly due to these increased physical health risks, the current evidence for pharmacological and non-pharmacological interventions in people with schizophrenia to prevent and treat these conditions is still limited and more larger trials are urgently needed.People with schizophrenia have substantially poorer physi cal health than the general population 14 , which is often attrib uted to an interaction between social circumstances, lifestyle factors and treatment effects 5 . For instance, behavioral re search has demonstrated that people with schizophrenia are less physically active and exhibit more sedentary behavior than the general population 6 , have a higher quantity but lower qual ity of dietary food intake 7 , and increased adverse health behav iors, such as smoking 8 . Additionally, psychiatric treatment with antipsychotics and other commonly prescribed agents, such as mood stabilizers and antidepressants, further increases the risk of physical health conditions 9,10 . Consequently, people with schizophrenia more frequently have cardiometabolic diseases 1113 , respiratory d...

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Section: Resultsmentioning

confidence: 98%

“…Of 3,709 search engine hits, 27 meta‐analyses were included, representing a total of 128 meta‐analyzed trials and 47,231 study participants.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The impact of pharmacological and non‐pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta‐review of meta‐analyses of randomized controlled trials

et al. 2019

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“…Although schizophrenia is typically associated with the greatest degree of cardiovascular risk (partly due to the side-effects of antipsychotic medications), there is now compelling evidence that obesity, metabolic syndrome, diabetes and cardiometabolic disease are similarly elevated in other mental disorders, including CMDs. [26][27][28][29][66][67][68][69][70][71][72][73] Given the higher prevalence of these mental disorders across the population, developing transdiagnostically-applicable strategies for improving cardiometabolic health outcomes in these populations (along with SMIs) could considerably reduce the premature mortality and lifelong burden of poor physical health which affects people with mental illness across the globe. Within this, the impact and prevalence of other NCDs and infectious diseases, in both high income and LMIC setting, cannot be neglected.…”

Section: Further Considerations On Physical-mental Comorbiditiesmentioning

confidence: 99%

“…Part 1 identified cardiometabolic diseases as a category of physical comorbidities that are particularly pervasive and impactful on well-being, morbidity and mortality, across many mental disorders. [26][27][28][29][55][56][57][66][67][68][69][70][71][72][73]82 Along with side-effects of psychotropic medications (covered in Part 3), reasons for the increased cardiometabolic morbidity and mortality in people with mental illness can be divided into patient-related and provider/system-level factors. 25 Clear modifiable patient-related factors known to heavily influence cardiometabolic diseases are 'lifestyle risk factors' such as smoking, poor diet, and inactivity 35,[83][84][85] ; adverse health behaviours which also influence many other aspects of physical health.…”

Section: Introductionmentioning

confidence: 99%

The Lancet Psychiatry Commission: a blueprint for protecting physical health in people with mental illness

Firth

Siddiqi

Koyanagi

et al. 2019

The Lancet Psychiatry

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Executive SummaryThe poor physical health of people with mental illness is a multi-faceted, transdiagnostic, and global problem. Physical health disparities are observed across the entire spectrum of mental illnesses, in low, middle-and high-income countries. This stems from both a heightened risk of physical diseases in people with mental illness, along with their reduced access to adequate healthcare. The high rates of physical comorbidities (and typically-poor clinical management of this) drastically reduces life expectancy, and also increases the personal, social and economic burden of illness across the lifespan.This Commission has brought together an international team of researchers, clinicians, and key stakeholders from various backgrounds and professionally / personally-relevant experience, in order to summarize advances in understanding on this topic, and present clear directions for health promotion, clinical care and future research. The breadth and multifactorial nature of physical health disparities across the range of mental health diagnoses poses an almost limitless number of potential considerations. Therefore, rather than attempting to cover all of the different possible combinations of physical-mental comorbidities individually, the aim of this Commission was to: (i) establish highlypertinent aspects of physical health-related morbidity and mortality which apply transdiagnostically, (ii) highlight the common modifiable factors driving these disparities, (iii) present actions and initiatives for health policy and clinical services to address these issues, and (iv) identify promising areas for future research towards discovering novel solutions. This was addressed across 5 different Parts of the Commission: Parts 1 and 2 determined the scope, priorities and key targets for physical health improvement across multiple mental illnesses. Parts 3, 4 and 5 discussed emerging strategies and produced recommendations for improving physical health outcomes in people with mental illness. Leaders and contributors for each Part are shown in the Appendix (pg.1) . Part 1: 'Its more than premature mortality'Part 1 identified almost 100 systematic reviews/meta-analyses examining the prevalence of physical comorbidities in mental illness. Around 70% of the meta-research focused on cardiometabolic diseases; consistently reporting that mental illnesses were associated with 1.4-to 2-fold increased risk for obesity, diabetes and cardiovascular diseases compared to the general population. Although mostly studied in 'severe mental illness' ('SMI', and particularly psychotic disorders), the prevalence of cardiometabolic diseases was similarly elevated across a broad range of other diagnoses, including substance use disorders (SUDs), and 'common mental disorders' ('CMDs', such as depression and anxiety). Part 2: Key modifiable factors in health behaviours and health servicesPart 2 built on the findings of Part 1 with a hierarchal evidence synthesis of modifiable risk factors for physical diseases in mental illness. The bu...

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Mental Disorders and Diabetes

Siddiqi,

Stadler,

Holt

2024

Textbook of Diabetes

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Glucagon‐like peptide‐1 receptor agonists for antipsychotic‐associated cardio‐metabolic risk factors: A systematic review and individual participant data meta‐analysis

Abstract: GLP-1RAs are effective and tolerable for antipsychotic-associated body weight gain, particularly clozapine/olanzapine-treated patients. With few included patients, further studies are required before making routine use recommendations for GLP-1RAs.

Cited by 87 publications

References 59 publications

The impact of pharmacological and non‐pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta‐review of meta‐analyses of randomized controlled trials

The impact of pharmacological and non‐pharmacological interventions to improve physical health outcomes in people with schizophrenia: a meta‐review of meta‐analyses of randomized controlled trials

The Lancet Psychiatry Commission: a blueprint for protecting physical health in people with mental illness

Mental Disorders and Diabetes

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