Metformin for the Prevention of the Metabolic Side-effects of Zyprexa

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00682448
Recruitment Status : Completed
First Posted : May 22, 2008
Last Update Posted : December 12, 2012
Eli Lilly and Company
Information provided by (Responsible Party):
Jeffrey Rado, MD, Rush University Medical Center

Brief Summary:
We hypothesize that metformin co-administered with olanzapine will be well tolerated and associated with significantly less insulin resistance, weight gain and dyslipidemia as compared to olanzapine plus placebo.

Condition or disease Intervention/treatment Phase
Metabolic Complications Drug: Metformin Drug: Placebo Phase 4

Detailed Description:
Increased risk of metabolic complications with olanzapine therapy, relative to other antipsychotics, may lead clinicians to avoid its use, despite evidence of greater efficacy. These problems may also pose a therapeutic dilemma for patients who respond well to olanzapine. Metabolic complications negatively impact on morbidity and mortality, impair quality of life and increase illness relapse secondary to medication non-compliance. Thus far, no pharmacologic agent co-administered with olanzapine has proven effective at preventing these untoward effects. The present study proposes to examine the efficacy and safety of metformin to attenuate the metabolic side effects associated with olanzapine.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Metformin to Prevent the Metabolic Complications of Olanzapine
Study Start Date : August 2007
Actual Primary Completion Date : August 2011
Actual Study Completion Date : August 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: 1
Olanzapine plus metformin: olanzapine plus metformin 500 mg titrated up to but no greater than 2,000 mg based upon fasting blood glucose during study visits over six months.
Drug: Metformin
Drug: Metformin 500 mg po daily titrated up to but no greater than 2000 mg based upon fasting blood glucose during study visits over six months.
Other Names:
  • Glucophage
  • Fortamet
  • Riomet
  • Glumetza
  • Diabex
  • Diaformin
Placebo Comparator: 2
Olanzapine plus Drug: Placebo. Subjects will remain on olanzapine plus placebo for 6 months.
Drug: Placebo
Drug: Placebo. Subjects will remain on placebo for 6 months.

Primary Outcome Measures :
  1. Weight Gain and Insulin Resistance [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Dislipidemia, OGTT, Hemoglobin A1C [ Time Frame: 6 months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of: Schizophrenia, Schizoaffective Disorder, Bipolar I or II or major depression with psychotic features who will be started on or who have just started taking Olanzapine (Zyprexa).

Exclusion Criteria:

  • Patients with either a history of diabetes mellitus or a baseline FBG>126 or two random blood sugars of > 200 or during a OGTT glucose level of > 200 two hours after a glucose load of 50 grams. (All American Diabetes Association criteria for diabetes mellitus).
  • Baseline liver function tests (SGOT, SGPT, AP) greater than 3X normal.
  • Chronic alcoholism
  • MDRD less than 60 ml/1.73 m2. Modification of Diet in Renal Disease (MDRD) Equation estimates the glomerular filtration rate as a measure of kidney function. This equation takes into account the plasma creatinine, age, race and gender, and is a more accurate estimation of glomerular filtration rate than serum creatinine alone.
  • Patients with unstable medical problems, including cardiovascular instability or significant congestive heart failure (as determined by study investigators).
  • Prolonged QTc greater than 430 ms on baseline EKG.
  • History of lactic acidosis.
  • History of hypoglycemia.
  • Current treatment with metformin or other antidiabetic agents.
  • Treatment with any antihyperlipidemic medication within 3 months of randomization.
  • Treatment with olanzapine or clozapine within 3 months of randomization.
  • Concurrent treatment with ziprasidone, risperidone, quetiapine or aripiprazole or any other neuroleptic medication.
  • Concurrent use of OTC chromium, gymnema or cimetidine will be prohibited. Patient may discontinue these medications up to one day prior to randomization.
  • Current treatment with corticosteroids.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00682448

United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
Sponsors and Collaborators
Rush University Medical Center
Eli Lilly and Company
Principal Investigator: Jeffrey T Rado, M.D. Rush University Medical Center

Responsible Party: Jeffrey Rado, MD, MD, Rush University Medical Center Identifier: NCT00682448     History of Changes
Other Study ID Numbers: 06122201
First Posted: May 22, 2008    Key Record Dates
Last Update Posted: December 12, 2012
Last Verified: December 2012

Keywords provided by Jeffrey Rado, MD, Rush University Medical Center:
Weight Gain
Bipolar Disorder
Side effects
Metabolic complications
Metabolic side effects of olanzapine

Additional relevant MeSH terms:
Hypoglycemic Agents
Physiological Effects of Drugs
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents