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

Metformin to Prevent the Metabolic Complications of Olanzapine

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.

Study Overview

• Status: Completed
• Conditions: Metabolic Complications
• Intervention / Treatment: Drug: Metformin; Drug: Placebo

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
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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; Glumetza; Fortamet; Riomet; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight Gain	Change from Baseline in weight	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin A1C	change from baseline in hemoglobin AIC	Baseline and 6 months

Collaborators and Investigators

• Sponsor: Rush University Medical Center
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Jeffrey T Rado, M.D., Rush University Medical Center

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (ACTUAL): August 1, 2011
• Study Completion (ACTUAL): August 1, 2011

Study Registration Dates

• First Submitted: May 20, 2008
• First Submitted That Met QC Criteria: May 21, 2008
• First Posted (ESTIMATE): May 22, 2008

Study Record Updates

• Last Update Posted (ACTUAL): February 2, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Depression; Treatment; Diabetes; Schizophrenia; Metformin; Bipolar Disorder; Prevention; Weight Gain; Antipsychotics; Olanzapine; Side effects; Glucophage; Zyprexa; Metabolic complications; Metabolic side effects of olanzapine
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 06122201