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Letters to the Editor   |    
Sustained Weight Loss After Treatment With a Glucagon-Like Peptide-1 Receptor Agonist in an Obese Patient With Schizophrenia and Type 2 Diabetes
Pelle L. Ishøy, M.D.; Filip K. Knop, M.D., Ph.D.; Tina Vilsbøll, M.D., D.M.SC.; Birte Y. Glenthøj, M.D., D.M.SC.; Bjørn H. Ebdrup, M.D., Ph.D.
Am J Psychiatry 2013;170:681-682. doi:10.1176/appi.ajp.2013.12101344
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Dr. Knop has received lecture, consulting, or advisory board membership fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly Danmark A/S, Gilead Sciences, Merck Sharp and Dohme, Novo Nordisk, Ono Pharmaceuticals, Sanofi, and Zealand Pharma. Dr. Vilsbøll has received consulting, lecture, or advisory board fees from AstraZeneca, Bohringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp and Dohme, Novartis, Novo Nordisk, Sanofi Aventis, and Zealand Pharma. Dr. Ebdrup has received lecture or advisory board fees from Bristol-Myers Squibb and Eli Lilly Danmark A/S. Drs. Ishøy and Glenthøj report no financial relationships with commercial interests.

Supported by grants from the University of Copenhagen awarded to Dr. Ishøy (211-0649/11-3012) and from the University of Copenhagen/Mental Health Services, Capital Region of Denmark, awarded to Dr. Ebdrup. The Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research was funded by a Lundbeck Foundation grant (R25-A2701).

From the Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Faculty of Health Sciences, Psychiatric Center Glostrup, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark, and the Diabetes Research Division, Department of Internal Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.

Copyright © 2013 by the American Psychiatric Association

Accepted February , 2013.

To the Editor: Obesity, diabetes, and cardiovascular disease associated with antipsychotics represent major unresolved clinical issues that contribute to the increasing mortality gap between patients with schizophrenia and the general population (1). At best, current interventions against antipsychotic-induced weight gain (e.g., metformin) facilitate a weight loss of up to 3 kg, but the long-term stability of this weight reduction is questionable (2). Glucagon-like peptide-1 (GLP-1) receptor agonists efficiently reduce blood glucose levels and confer only a negligible risk of hypoglycemia. For these reasons, GLP receptor agonists are widely used in the treatment of type 2 diabetes. GLP-1 receptor agonists stimulate glucose-induced insulin secretion, inhibit glucagon secretion, and reduce gastrointestinal motility, which reduce appetite and food intake. Ultimately, this also leads to weight loss in patients without type 2 diabetes (3). Currently, Novo Nordisk is pursuing U.S. Food and Drug Administration approval for liraglutide for obesity.

This case report describes the effects of GLP-1 receptor agonist treatment in a schizophrenia patient with antipsychotic-induced obesity and type 2 diabetes. The patient provided consent for publication.

A 60-year-old woman with clozapine-treated disorganized schizophrenia (hebephrenia) and a past history of drug abuse was referred to our diabetes outpatient clinic for dysregulated type 2 diabetes. The patient had been living in supported housing for 19 years.

Clinical and biochemical data from somatic and psychiatric records covering a 2-year period were obtained. At referral, the patient weighed 89 kg (body mass index, 33.5), and her glycated hemoglobin A1c (HbA1c) level was 10.0%. She was being treated with clozapine (375 mg/day), insulin (44 IU/day, biphasic insulin aspart), metformin (2 g/day), and simvastatin (10 mg/day). We initiated add-on treatment with liraglutide (0.6 mg/day, subcutaneous injection), which was well tolerated, and self-administration was uncomplicated. After 3 weeks, the liraglutide dosage was increased to 1.2 mg/day, and after 8 months it was increased to 1.8 mg/day.

Three months of treatment reduced her HbA1c level to 8.9% and her body weight by 5.1 kg. After 2 years of treatment, her total weight loss was 7.7 kg (an 8.7% body weight reduction) (Figure 1). After 14 months, her HbA1c level was less than 6.5%, and the amount of insulin needed gradually decreased (28 IU/day). The patient’s lifestyle and psychiatric status were stable during the 2-year period (a score of 30 on the Global Assessment of Functioning Scale), without hospital admissions.

 
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FIGURE 1.Body Weight and Glycated Hemoglobin A1c (HbA1c) Levels During 2 Years of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Treatmenta

a Body weight timeline (blue line) and HbA1c (red line) over 2 years of GLP-1 receptor agonist treatment in an obese patient with schizophrenia and dysregulated type 2 diabetes (baseline body mass index, 33.5). The dotted red line indicates the reference value for HbA1c used to define diabetes (≥6.5%). Black triangles on the x-axis indicate time points and dosage increases of the GLP-1 receptor agonist liraglutide.

Two years of liraglutide treatment markedly decreased HbA1c levels and resulted in a substantial weight loss in an obese patient with schizophrenia and dysregulated diabetes. To our knowledge, this is the first clinical evidence supporting the use of GLP-1 receptor agonists in the treatment of antipsychotic-induced weight gain (2).

Saha  S;  Chant  D;  McGrath  J:  A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry 2007; 64:1123–1131
[CrossRef] | [PubMed]
 
Ebdrup  BH;  Knop  FK;  Ishøy  PL;  Rostrup  E;  Fagerlund  B;  Lublin  H;  Glenthøj  B:  Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits.  BMC Med 2012; 10:92
[CrossRef] | [PubMed]
 
Vilsbøll  T;  Christensen  M;  Junker  AE;  Knop  FK;  Gluud  LL:  Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomized controlled trials.  BMJ 2012; 344:d7771
[CrossRef] | [PubMed]
 
References Container

FIGURE 1. Body Weight and Glycated Hemoglobin A1c (HbA1c) Levels During 2 Years of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Treatmenta

a Body weight timeline (blue line) and HbA1c (red line) over 2 years of GLP-1 receptor agonist treatment in an obese patient with schizophrenia and dysregulated type 2 diabetes (baseline body mass index, 33.5). The dotted red line indicates the reference value for HbA1c used to define diabetes (≥6.5%). Black triangles on the x-axis indicate time points and dosage increases of the GLP-1 receptor agonist liraglutide.

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References

Saha  S;  Chant  D;  McGrath  J:  A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry 2007; 64:1123–1131
[CrossRef] | [PubMed]
 
Ebdrup  BH;  Knop  FK;  Ishøy  PL;  Rostrup  E;  Fagerlund  B;  Lublin  H;  Glenthøj  B:  Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits.  BMC Med 2012; 10:92
[CrossRef] | [PubMed]
 
Vilsbøll  T;  Christensen  M;  Junker  AE;  Knop  FK;  Gluud  LL:  Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomized controlled trials.  BMJ 2012; 344:d7771
[CrossRef] | [PubMed]
 
References Container
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