Glucagon-like peptide-1 agonists combating clozapine-associated obesity and diabetes

Mayfield, Karla; Siskind, Dan; Winckel, Karl; Russell, Anthony W; Kisely, Steve; Smith, Greg; Hollingworth, Samantha

doi:10.1177/0269881115625496

Cited by 49Diabetes Treatment and ManagementSchizophrenia research and treatmentPharmacology and Obesity Treatment

Glucagon-like peptide-1 agonists combating clozapine-associated obesity and diabetes

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Mayfield, Karla, Siskind, Dan, Winckel, Karl, Russell, Anthony W, Kisely, Steve, Smith, Greg, Hollingworth, Samantha·2016·Journal of Psychopharmacology

DOI 10.1177/0269881115625496

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Abstract

Clozapine is the most effective antipsychotic, but its use is tempered by adverse metabolic effects such as weight gain, glucose intolerance and type II diabetes. Current interventions do not facilitate compelling or sustained improvement in metabolic status. Recent studies suggest that glucagon-like peptide-1 (GLP-1) may play a key role in clozapine's metabolic effects, possibly suggesting that clozapine-associated obesity and diabetes are mediated independently through reduced GLP-1. As a result, GLP-1 agonists could show promise in reversing antipsychotic-induced metabolic derangements, providing mechanistic justification that they may represent a novel approach to treat, and ultimately prevent, both diabetes and obesity in patients on clozapine. GLP-1 agonists are already used for diabetes, and they provide a unique combination of glycaemic improvement and metabolically relevant weight loss in diabetic and non-diabetic patients, in the context of a currently favourable safety proﬁle. Using GLP-1 agonists for clozapine-associated obesity and diabetes could be a potentially effective intervention that may reduce cardiometabolic morbidity and mortality in this vulnerable patient population.

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Drawing on advances in implementation science will make lifestyle interventions more likely to meaningfully impact patient outcomes.
“Drawing on advances in implementation science will also make lifestyle interventions more likely to meaningfully impact patient outcomes.243”
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Glucagon-like peptide analogues for type 2 diabetes mellitus: systematic review and meta-analysis
Shyangdan, D., Royle, P., Clar, C., Sharma, P., & Waugh, N. R. (2010) · BMC Endocrine Disorders · doi:10.1186/1472-6823-10-20 · Cited by 88 · see citing works
Atypical antipsychotic drugs induce derangements in glucose homeostasis by acutely increasing glucagon secretion and hepatic glucose output in the rat
Smith, G. C., Chaussade, C., Vickers, M. H., Jensen, J., & Shepherd, P. R. (2008) · Diabetologia · doi:10.1007/s00125-008-1152-3 · Cited by 87 · see citing works
Systematic Review and Meta-analysis of Pharmacological Interventions for Weight Gain from Antipsychotics and Mood Stabilizers
Fiedorowicz, J. G., Miller, D. D., Bishop, J. R., Calarge, C. A., Ellingrod, V. L., & Haynes, W. G. (2012) · Current Psychiatry Reviews · doi:10.2174/157340012798994867 · Cited by 79 · see citing works
Retrospective Study of Adherence to Glucagon-like Peptide-1 Receptor Agonist Therapy in Patients with Type 2 Diabetes Mellitus in the United States
Johnston, S. S., Nguyen, H. P., Felber, E., Cappell, K. A., Nelson, J. K., Chu, B. C., & Kalsekar, I. D. (2014) · Advances in Therapy · doi:10.1007/s12325-014-0166-0 · Cited by 71 · see citing works
Evaluation of Insulin Sensitivity in Healthy Volunteers Treated with Olanzapine, Risperidone, or Placebo: A Prospective, Randomized Study Using the Two-Step Hyperinsulinemic, Euglycemic Clamp
Sowell, M. O., Mukhopadhyay, N. D., Cavazzoni, P. A., Carlson, C. D., Mudaliar, S. R. D., Chinnapongse, S., Ray, A. J., Davis, T., Breier, A. F., Henry, R. R., et al. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021884 · Cited by 69 · see citing works
GLP-1 receptor agonist liraglutide reverses long-term atypical antipsychotic treatment associated behavioral depression and metabolic abnormalities in rats
Sharma, A. N., Ligade, S. S., Sharma, J. N., Shukla, P., Elased, K. M., & Lucot, J. B. (2014) · Metabolic Brain Disease · doi:10.1007/s11011-014-9591-7 · Cited by 66 · see citing works
Weight loss effect of glucagon‐like peptide‐1 mimetics on obese/overweight adults without diabetes: A systematic review and meta‐analysis of randomized controlled trials胰高血糖素样肽‐1类似物对非糖尿病肥胖/超重成人的减重作用：一篇对随机对照试验进行的系统评价及meta分析
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Clozapine and quetiapine acutely reduce glucagon-like peptide-1 production and increase glucagon release in obese rats: Implications for glucose metabolism and food choice behaviour
Smith, G. C., Vickers, M. H., Cognard, E., & Shepherd, P. R. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.07.011 · Cited by 58 · see citing works
Efficacy and tolerability of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus
Harris, K. B., & McCarty, D. J. (2014) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018814558242 · Cited by 57 · see citing works
A Glucagon-Like Peptide-1 Receptor Agonist and an Antagonist Modify Macronutrient Selection by Rats
Peters, C. T., Choi, Y.-H., Brubaker, P. L., & Anderson, G. H. (2001) · Journal of Nutrition · doi:10.1093/jn/131.8.2164 · Cited by 52 · see citing works
The once-daily human GLP-1 analog, liraglutide, reduces olanzapine-induced weight gain and glucose intolerance
Lykkegaard, K., Larsen, P. J., Vrang, N., Bock, C., Bock, T. G., & Knudsen, L. B. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.05.011 · Cited by 52 · see citing works
A new blood glucose management algorithm for type 2 diabetes: a position statement of the Australian Diabetes Society
Gunton, J. E., Cheung, N. W., Davis, T. M. E., Zoungas, S., & Colagiuri, S. (2014) · The Medical Journal of Australia · doi:10.5694/mja14.01187 · Cited by 51 · see citing works
Glucagon-like peptide-1 (GLP-1) receptor agonist prevents development of tolerance to anti-anxiety effect of ethanol and withdrawal-induced anxiety in rats
Sharma, A. N., Pise, A., Sharma, J. N., & Shukla, P. (2014) · Metabolic Brain Disease · doi:10.1007/s11011-014-9627-z · Cited by 50 · see citing works
Exenatide once weekly: sustained improvement in glycemic control and cardiometabolic measures through 3 years
Remillard, C. V., MacConell, Li, Pencek, Maggs, & Porter (2013) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s35801 · Cited by 48 · see citing works
Olanzapine effects on body composition, food preference, glucose metabolism and insulin sensitivity in the rat
Smith, G. C., Vickers, M. H., & Shepherd, P. R. (2011) · Archives of Physiology and Biochemistry · doi:10.3109/13813455.2011.576681 · Cited by 48 · see citing works
Antipsychotic-like effect of GLP-1 agonist liraglutide but not DPP-IV inhibitor sitagliptin in mouse model for psychosis
Dixit, T. S., Sharma, A. N., Lucot, J. B., & Elased, K. M. (2013) · Physiology & Behavior · doi:10.1016/j.physbeh.2013.03.008 · Cited by 46 · see citing works
Therapies for inter-relating diabetes and obesity – GLP-1 and obesity
Iepsen, E. W., Torekov, S. S., & Holst, J. J. (2014) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2014.965678 · Cited by 43 · see citing works
Treatment of clozapine-associated weight gain: a systematic review
Whitney, Z., Procyshyn, R. M., Fredrikson, D. H., & Barr, A. M. (2015) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-015-1807-1 · Cited by 42 · see citing works
A double‐blind, placebo‐controlled trial of rosiglitazone for clozapine‐induced glucose metabolism impairment in patients with Schizophrenia
Henderson, D. C., Fan, X., Sharma, B., Copeland, P. M., Borba, C. P. C., Boxill, R., Freudenreich, O., Cather, C., Evins, A. E., & GOFF, D. C. (2009) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2008.01325.x · Cited by 39 · see citing works
Short-term treatment with olanzapine does not modulate gut hormone secretion: olanzapine disintegrating versus standard tablets
Vidarsdóttir, S., Roelfsema, F., Streefland, T. C. M., Holst, J. J., Rehfeld, J. F., & Pijl, H. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0433 · Cited by 37 · see citing works
Diabetes Mellitus Among Outpatients Receiving Clozapine
Lamberti, J. S., Costea, G. O., Olson, D. P., Crilly, J. F., Maharaj, K., Tu, X. M., Groman, A. E., Dietz, M. B., Bushey, M. P., Olivares, T. E., et al. (2005) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v66n0713 · Cited by 36 · see citing works
Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits
Ebdrup, B. H., Knop, F. K., Ishøy, P. L., Rostrup, E., Fagerlund, B., Lublin, H., & Glenthøj, B. (2012) · BMC Medicine · doi:10.1186/1741-7015-10-92 · Cited by 34 · see citing works
Dietary Saturated Fat Intake and Glucose Metabolism Impairments in Nondiabetic, Nonobese Patients with Schizophrenia on Clozapine Or Risperidone
Henderson, D. C., Sharma, B., Fan, X., Copeland, P. M., Borba, C. P. C., Freudenreich, O., Cather, C., Evins, A. E., & GOFF, D. C. (2010) · Annals of Clinical Psychiatry · doi:10.1177/104012371002200106 · Cited by 28 · see citing works
Clozapine directly increases insulin and glucagon secretion from islets: Implications for impairment of glucose tolerance
Smith, G. C., Zhang, Z. Y., Mulvey, T. B., Petersen, N., Lach, S., Xiu, P., Phillips, A. R. J., Han, W., Wang, M.-W., & Shepherd, P. R. (2014) · Schizophrenia Research · doi:10.1016/j.schres.2014.05.003 · Cited by 28 · see citing works
Dipeptidyl-peptidase IV (DPP-IV) inhibitor delays tolerance to anxiolytic effect of ethanol and withdrawal-induced anxiety in rats
Sharma, A. N., Pise, A., Sharma, J. N., & Shukla, P. (2014) · Metabolic Brain Disease · doi:10.1007/s11011-014-9603-7 · Cited by 28 · see citing works
Sustained Weight Loss After Treatment With a Glucagon-Like Peptide-1 Receptor Agonist in an Obese Patient With Schizophrenia and Type 2 Diabetes
Ishøy, P. L., Knop, F. K., Vilsbøll, T., Glenthoj, B. Y., & Ebdrup, B. H. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.12101344 · Cited by 28 · see citing works
Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist—protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study: the TAO study protocol
Ishøy, P. L., Knop, F. K., Broberg, B. V., Baandrup, L., Fagerlund, B., Jørgensen, N. R., Andersen, U. B., Rostrup, E., Glenthoj, B. Y., & Ebdrup, B. H. (2014) · BMJ Open · doi:10.1136/bmjopen-2013-004158 · Cited by 24 · see citing works
Glucometabolic Hormones and Cardiovascular Risk Markers in Antipsychotic-Treated Patients
Ebdrup, B. H., Knop, F. K., Madsen, A., Mortensen, H. B., Søgaard, B., Holst, J. J., Szecsi, P. B., & Lublin, H. (2014) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.13m08820 · Cited by 21 · see citing works
Does a GLP-1 receptor agonist change glucose tolerance in patients treated with antipsychotic medications? Design of a randomised, double-blinded, placebo-controlled clinical trial
Larsen, J., Vedtofte, L., Holst, J., Oturai, P., Kjær, A., Corell, C. U., Vilsbøll, T., & Fink-Jensen, A. (2014) · BMJ Open · doi:10.1136/bmjopen-2013-004227 · Cited by 20 · see citing works
Treatment of clozapine-associated obesity and diabetes with exenatide (CODEX) in adults with schizophrenia: study protocol for a pilot randomised controlled trial
Mayfield, K., Siskind, D. J., Winckel, K., Hollingworth, S., Kisely, S. R., & Russell, A. W. (2015) · BJPsych Open · doi:10.1192/bjpo.bp.115.001073 · Cited by 12 · see citing works
Genetic Variation in the GCG and in the GLP1R Genes and Antipsychotic-Induced Weight Gain
Brandl, E. J., Tiwari, A. K., Chowdhury, N. I., Zai, C. C. H., Lieberman, J. A., Meltzer, H. Y., Kennedy, J. L., & Müller, D. J. (2014) · Pharmacogenomics · doi:10.2217/pgs.13.247 · Cited by 12 · see citing works

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The Lancet Psychiatry Commission: a blueprint for protecting physical health in people with mental illness
Firth, J., Siddiqi, N., Koyanagi, A., Siskind, D., Rosenbaum, S., Galletly, C., Allan, S., Caneo, C., Carney, R., Carvalho, A. F., et al. (2019) · The Lancet Psychiatry · doi:10.1016/s2215-0366(19)30132-4 · Cited by 1,531 · see citing works
Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences
Carli, M., Kolachalam, S., Longoni, B., Pintaudi, A. M., Baldini, M., Aringhieri, S., Fasciani, I., Annibale, P., Maggio, R., & Scarselli, M. (2021) · Pharmaceuticals · doi:10.3390/ph14030238 · Cited by 252 · see citing works
Effect of Liraglutide Treatment on Prediabetes and Overweight or Obesity in Clozapine- or Olanzapine-Treated Patients With Schizophrenia Spectrum Disorder: A Randomized Clinical Trial
Larsen, J. R., Vedtofte, L., Jakobsen, M. S. L., Jespersen, H. R., Jakobsen, M. I., Svensson, C. K., Koyuncu, K., Schjerning, O., Oturai, P. S., Kjaer, A., et al. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.1220 · Cited by 250 · see citing works
Glucagon‐like peptide‐1 receptor agonists for antipsychotic‐associated cardio‐metabolic risk factors: A systematic review and individual participant data meta‐analysis
Siskind, D., Hahn, M., Correll, C. U., Fink‐Jensen, A., Russell, A. W., Bak, N., Broberg, B. V., Larsen, J., Ishøy, P. L., Vilsbøll, T., et al. (2019) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13522 · Cited by 144 · see citing works
Self-citation
Metformin for clozapine associated obesity: a systematic review and meta-analysis
Siskind, D. J., Leung, J., Russell, A. W., Wysoczanski, D., & Kisely, S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0156208 · Cited by 122 · see citing works
Self-citation
Treatment of clozapine‐associated obesity and diabetes with exenatide in adults with schizophrenia: <scp>A</scp> randomized controlled trial ( <scp>CODEX</scp> )
Siskind, D. J., Russell, A. W., Gamble, C., Winckel, K., Mayfield, K., Hollingworth, S., Hickman, I., Siskind, V., & Kisely, S. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13167 · Cited by 98 · see citing works
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A Focused Review of the Metabolic Side-Effects of Clozapine
Yuen, J. W. Y., Kim, D. D., Procyshyn, R. M., Panenka, W. J., Honer, W. G., & Barr, A. M. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.609240 · Cited by 92 · see citing works
Understanding the Effects of Antipsychotics on Appetite Control
Mukherjee, S., Skrede, S., Milbank, E., Andriantsitohaina, R., López, M., & Fernø, J. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2021.815456 · Cited by 68 · see citing works
One-year follow-up on liraglutide treatment for prediabetes and overweight/obesity in clozapine- or olanzapine-treated patients
Svensson, C. K., Larsen, J. R., Vedtofte, L., Jakobsen, M. S. L., Jespersen, H. R., Jakobsen, M. I., Koyuncu, K., Schjerning, O., Nielsen, J., Ekstrøm, C. T., et al. (2019) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12982 · Cited by 66 · see citing works
Strategies to counter antipsychotic-associated weight gain in patients with schizophrenia
Marteene, W., Winckel, K., Hollingworth, S., Kisely, S. R., Gallagher, E., Hahn, M., Ebdrup, B. H., Firth, J., & Siskind, D. J. (2019) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2019.1674809 · Cited by 62 · see citing works
Therapeutic management of atypical antipsychotic‑related metabolic dysfunctions using GLP‑1 receptor agonists: A systematic review
Vasiliu, O. (2023) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2023.12054 · Cited by 60 · see citing works
Recognition and management of clozapine adverse effects: A systematic review and qualitative synthesis
Gurrera, R. J., Gearin, P. F., Love, J., Li, K. J., Xu, A., Donaghey, F., & Gerace, M. R. (2022) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.13406 · Cited by 58 · see citing works
The pleiotropic of GLP-1/GLP-1R axis in central nervous system diseases
Zhang, L., Zhang, W., & Tian, X. (2023) · International Journal of Neuroscience · doi:10.1080/00207454.2021.1924707 · Cited by 54 · see citing works
Efficacy and safety of semaglutide versus placebo for people with schizophrenia on clozapine with obesity (COaST): a phase 2, multi-centre, participant and investigator- blinded, randomised controlled trial in Australia.
Siskind, D., Baker, A., Arnautovska, U., Warren, N., Russell, A., DeMonte, V., Halstead, S., Iyer, R., Korman, N., McKeon, G., et al. (2025) · The Lancet Psychiatry · doi:10.1016/s2215-0366(25)00129-4 · Cited by 62 · see citing works
Immune and metabolic alterations in first episode psychosis (FEP) patients
Bocchio‐Chiavetto, L., Zanardini, R., Tosato, S., Ventriglia, M., Ferrari, C., Bonetto, C., Lasalvia, A., Giubilini, F., Fioritti, A., Pileggi, F., et al. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.03.013 · Cited by 41 · see citing works
Glucagon-like peptide-1 receptor-agonists treatment for cardio-metabolic parameters in schizophrenia patients: a systematic review and meta-analysis
Khaity, A. M., Al-dardery, N. M., Albakri, K. A., Abdelwahab, O. A., Hefnawy, M. T., Yousef, Y. S. A. H., Taha, R. E. W., Swed, S., Hafez, W., Hurlemann, R., et al. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1153648 · Cited by 35 · see citing works
Risk factors, prevention and treatment of weight gain associated with the use of antidepressants and antipsychotics: a state-of-the-art clinical review
Solmi, M., Miola, A., Capone, F., Pallottino, S., Højlund, M., Firth, J., Siskind, D. J., Holt, R. I. G., Corbeil, O., Cortese, S., et al. (2024) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2024.2396396 · Cited by 33 · see citing works
High prevalence of prediabetes and metabolic abnormalities in overweight or obese schizophrenia patients treated with clozapine or olanzapine
Larsen, J. R., Svensson, C. K., Vedtofte, L., Jakobsen, M. S. L., Jespersen, H. S. R., Jakobsen, M. I., Koyuncu, K., Schjerning, O., Nielsen, J., Ekstrøm, C. T., et al. (2018) · CNS Spectrums · doi:10.1017/s1092852918001311 · Cited by 32 · see citing works
Metabolic syndrome in patients with schizophrenia: Underlying mechanisms and therapeutic approaches (Review)
Manta, A., Georganta, A., Roumpou, A., Zoumpourlis, V., Spandidos, D. A., Rizos, E. N., & Peppa, Μ. (2025) · Molecular Medicine Reports · doi:10.3892/mmr.2025.13479 · Cited by 38 · see citing works
Peripheral mechanisms of acute olanzapine induced metabolic dysfunction: A review of in vivo models and treatment approaches
Shamshoum, H., Medak, K. D., & Wright, D. C. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.113049 · Cited by 26 · see citing works
Metabolic monitoring and management among clozapine users
Tso, G., Kumar, P. R., Jayasooriya, T., Kisely, S. R., & Siskind, D. J. (2016) · Australasian Psychiatry · doi:10.1177/1039856216665282 · Cited by 26 · see citing works
Does the gut microbiome mediate antipsychotic-induced metabolic side effects in schizophrenia?
Vasileva, S. S., Tucker, J., Siskind, D. J., & Eyles, D. W. (2022) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2022.2042251 · Cited by 20 · see citing works
Metabolic measures 12 months after a randomised controlled trial of treatment of clozapine associated obesity and diabetes with exenatide (CODEX)
Siskind, D. J., Russell, A. W., Gamble, C., Baker, A., Cosgrove, P., Burton, L., & Kisely, S. R. (2020) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2020.02.015 · Cited by 21 · see citing works
CoMET: a protocol for a randomised controlled trial of co-commencement of METformin as an adjunctive treatment to attenuate weight gain and metabolic syndrome in patients with schizophrenia newly commenced on clozapine
Siskind, D. J., Friend, N., Russell, A. W., McGrath, J. J., Lim, C. C. W., Patterson, S., Flaws, D., STEDMAN, T. J., Moudgil, V., Sardinha, S., et al. (2018) · BMJ Open · doi:10.1136/bmjopen-2017-021000 · Cited by 19 · see citing works
The Obesity–Impulsivity Axis: Potential Metabolic Interventions in Chronic Psychiatric Patients
Sfera, A., Osorio, C. P., Inderias, L., Parker, V., Price, A. I., & Cummings, M. A. (2017) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2017.00020 · Cited by 18 · see citing works
Rapid-onset clozapine-induced loss of glycaemic control: Case report
Porras‐Segovia, A., Krivoy, A., Horowitz, M. A., Thomas, G., Bolstridge, M., Ion, D., & Shergill, S. S. (2017) · BJPsych Open · doi:10.1192/bjpo.bp.117.004481 · Cited by 17 · see citing works
Genetic variants impacting metabolic outcomes among people on clozapine: a systematic review and meta-analysis
Suetani, R. J., Siskind, D. J., Reichhold, H., & Kisely, S. R. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4728-0 · Cited by 17 · see citing works
Interaction of clozapine with metformin in a schizophrenia rat model
Horváth, G., Kis, G., Kékesi, G., Büki, A., Adlan, L. G., Szűcs, E., Heni, H. E., & Benyhe, S. (2021) · Scientific Reports · doi:10.1038/s41598-021-96478-2 · Cited by 17 · see citing works
Do reductions in ghrelin contribute towards antipsychotic-induced weight gain?
Firth, J., Teasdale, S. B., Jackson, S. E., Vancampfort, D., Siskind, D. J., Sarris, J. J., & Solmi, M. (2018) · Schizophrenia Research · doi:10.1016/j.schres.2018.12.043 · Cited by 11 · see citing works
CoMET: a randomised controlled trial of co-commencement of metformin versus placebo as an adjunctive treatment to attenuate weight gain in patients with schizophrenia newly commenced on clozapine
Siskind, D. J., Russell, A. W., Suetani, S., Flaws, D., Kisely, S. R., Moudgil, V., Northwood, K. S., Robinson, G., Scott, J. G., STEDMAN, T. J., et al. (2021) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253211045248 · Cited by 10 · see citing works
The many facets of CD26/dipeptidyl peptidase 4 and its inhibitors in disorders of the CNS – a critical overview
Bernstein, H., Keilhoff, G., Dobrowolny, H., & Steiner, J. H. (2022) · Reviews in the Neurosciences · doi:10.1515/revneuro-2022-0026 · Cited by 10 · see citing works
Effects of semaglutide on body weight in clozapine-treated people with schizophrenia and obesity: study protocol for a placebo-controlled, randomised multicentre trial (COaST)
Siskind, D. J., Baker, A., Russell, A. W., Warren, N., Robinson, G., Parker, S., Medland, S. E., Kisely, S. R., Hager, T., & Arnautovska, U. (2023) · BJPsych Open · doi:10.1192/bjo.2023.532 · Cited by 9 · see citing works
Metformin reduces 12-month change in body weight among people newly commenced on clozapine: a retrospective naturalistic cohort study
Spokes, J., Hollingworth, S., Winckel, K., Kisely, S. R., Baker, A., Cosgrove, P., & Siskind, D. J. (2021) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253211000609 · Cited by 9 · see citing works
Schizophrenia and Related Psychoses
(2021) · Wiley eBooks · doi:10.1002/9781119870203.mpg001 · Cited by 8 · see citing works
Clozapine-Associated Hypothyroidism
Naguy, A., Moodliar-Rensburg, S., & Alamiri, B. (2020) · American Journal of Therapeutics · doi:10.1097/mjt.0000000000001244 · Cited by 7 · see citing works
Glucagon-like peptide-1 serum levels are associated with weight gain in patients treated with clozapine
Klemettilä, J.-P., Solismaa, A., Seppälä, N., Hämäläinen, M., Moilanen, E., Leinonen, E. V. J., & Kampman, O. (2021) · Psychiatry Research · doi:10.1016/j.psychres.2021.114227 · Cited by 7 · see citing works
Weight loss associated with exenatide in an obese man with diabetes commenced on clozapine
Siskind, D. J., Wysoczanski, D., Russell, A. W., & Ashford, M. E. (2016) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867416636243 · Cited by 6 · see citing works
Rapid-onset clozapine-induced hyperglycaemia: pathways of glycaemic dysregulation
Barbosa, M., & Fernandes, V. (2021) · BMJ Case Reports · doi:10.1136/bcr-2021-243938 · Cited by 5 · see citing works
Current strategies for predicting side effects from second generation antipsychotics in youth
Brown, J. T., Campo-Soria, C., & Bishop, J. R. (2021) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2021.1922668 · Cited by 5 · see citing works
Clozapine impaired glucose-stimulated insulin secretion partly by increasing plasma 5-HT levels due to the inhibition of OCT1-mediated hepatic 5-HT uptake in mice
Wu, W.-H., Zhi, H., Feng, W., Jiang, L., Lu, Y., Qian, L.-Q., Zhao, R.-X., Tan, Y.-M., Yang, H., Liu, X., et al. (2024) · Acta Pharmacologica Sinica · doi:10.1038/s41401-024-01401-w · Cited by 4 · see citing works
Using Routine Hemoglobin A1c Testing to Determine the Glycemic Status in Psychiatric Inpatients
Naidu, P., Churilov, L. P., Kong, A., Kanaan, R., Wong, H., van Mourik, A., Yao, A., Cornish, E., Hachem, M., Hart, G. K., et al. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00053 · Cited by 4 · see citing works
Augmentation Therapies as Treatments for Coexisting Somatic Problems in Schizophrenia—A Systematic Review
Dróżdż, W., Wiciński, M., Szota, A. M., Szambelan, M., Radajewska, I., Popławski, I., & Wojciechowski, P. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12124012 · Cited by 3 · see citing works
Fighting fire with fire: the need to use metformin to combat antipsychotic-induced weight gain and metabolic complications
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Approaches to mitigate weight gain associated with antipsychotic use
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Efficacy and safety of GLP-1 receptor agonists for antipsychotic-related overweight and metabolic dysregulation: a systematic review and meta-analysis
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Potential of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Mitigating Metabolic Side Effects Associated With Clozapine or Olanzapine Therapy: A Literature Review
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SA47. RCT of Exenatide for Clozapine-Associated Obesity
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Treatment of clozapine-associated obesity and diabetes with exenatide (CODEX) in adults with schizophrenia: study protocol for a pilot randomised controlled trial
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Treatment of clozapine‐associated obesity and diabetes with exenatide in adults with schizophrenia: <scp>A</scp> randomized controlled trial ( <scp>CODEX</scp> )
Siskind, D. J., Russell, A. W., Gamble, C., Winckel, K., Mayfield, K., Hollingworth, S., Hickman, I., Siskind, V., & Kisely, S. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13167 · Cited by 98 · see citing works
T160. TREATMENT OF CLOZAPINE-ASSOCIATED OBESITY AND DIABETES WITH EXENATIDE (CODEX) IN ADULTS WITH SCHIZOPHRENIA: A RANDOMISED CONTROLLED TRIAL
Siskind, D. J., Russell, A. W., Gamble, C., Winckel, K., Hollingworth, S., & Kisely, S. R. (2018) · Schizophrenia Bulletin · doi:10.1093/schbul/sby016.436 · Cited by 1 · see citing works

Authors: Mayfield, K., Siskind, D., Winckel, K., Russell, A. W., Kisely, S., Smith, G., & Hollingworth, S.
Affiliations: The University of Queensland (AU)
UNSW Sydney (AU)
Corresponding author: Siskind, Dan
ORCID: Siskind, Dan
Winckel, Karl
Russell, Anthony W
Kisely, Steve
Smith, Greg
Hollingworth, Samantha
Venue: Journal of Psychopharmacology
Publisher: SAGE Publications
Published: 2016-01-22
Volume: 30
Issue: 3
Pages: 227-236
ISSN: 0269-8811 (ISSN-L)
1461-7285
DOI: 10.1177/0269881115625496
OpenAlex: W2277996843
Cited by: 49
References: 107
Citations by year: 2026: 3 · 2025: 6 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 10 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 6 · 2016: 3
FWCI: 0.83
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: other-oa
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
Griffith Research Online (submittedVersion, other-oa)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
Keywords: clozapine, antipsychotic-induced obesity, antipsychotic-induced diabetes, glucagon-like peptide-1, GLP-1 receptor agonists, weight gain, impaired glucose tolerance, cardiometabolic risk, type 2 diabetes prevention
MeSH terms: Animals, Clozapine, Diabetes Mellitus, Type 2, Humans, Obesity, Antipsychotic Agents, Glucagon-Like Peptide 1

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Glucagon-like peptide-1 agonists combating clozapine-associated obesity and diabetes

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