Type II Diabetes Mellitus in Patients Exposed to Pravastatin and Paroxetine

Summary

Type 2 Diabetes (T2DM) is a life-long, chronic condition affecting an individuals' ability to regulate glucose levels in the blood. Diabetes can cause many severe complications if not treated properly. Hyperglycemia is a regular effect of uncontrolled diabetes and can lead to complications such as cardiovascular disease, chronic renal failure, diabetic retinopathy and inability to maintain a healthy body weight.

Cardiovascular Disease (CVD) is now the leading cause of death worldwide, affecting millions of people in both developed and non-developed countries. The buildup of cholesterol in the bloodstream may cause the excess to be deposited in the coronary arteries of the heart and the carotid arteries of the brain. The cholesterol deposits are a factor of the plaques that cause blockage of the arteries which can in turn lead to heart disease and stroke. By lowering the blood levels of cholesterol, risks of heart disease, strokes and heart attacks are reduced. Medications such as HMG-CoA reductase inhibitors and fibrates are useful in the prevention of CVD.

Pravastatin is a member of the drug class of statins, also known as HMG-CoA reductase inhibitors, and is shown as an adjunctive therapy to diet. It is known to reduce the amount of cholesterol and other fatty substances in the blood. In addition, pravastatin is indicated to reduce the risk of myocardial infarction, revascularization and cardiovascular mortality in hypercholesterolemic patients who do not have clinically apparent coronary heart disease. The recommended starting dose for adults is 40 mg once daily. For patients who do not reach the LDL-C goal with 40 mg, it is recommended to use an 80 mg dose. For persons with significant renal impairment the recommended dose is 10 mg. Children aged 8-13 years have a recommended starting dose of 20 mg daily. Adolescents aged 14 to 18 years have a recommended starting dose of 40 mg daily.

Depression is known as the most common mental disorder and most prevalent type of mood disorder today. It can be seen as a state of mood, a symptom, a syndrome or as a clinical diagnosis. Depression is a common disorder, affecting about 121 million people worldwide. Depression is more likely to co-occur with medical illnesses such as stroke, heart disease, cancer and diabetes. Up to one-quarter of people with diabetes are estimated to experience depression which is two times more than those who do not suffer from diabetes. Studies have shown that major depression mainly occurs in 2¬4 percent of people in the community, in 5-10 percent of primary care patients and 10-14 percent of medical inpatients. Also, recent studies have estimated that the symptoms continue over a 6 month to one year period in patients with major depression. The severity of the symptoms and the incidence of medical illness are expected to predict the persistence of depression. Depression can be treated effectively by a variety of antidepressants and/or psychotherapies. If treated appropriately, over 80 percent of people who suffer from depression can be helped.

Paroxetine is an orally administered selective serotonin reuptake inhibitor (SSRI) antidepressant. It was the first antidepressant that was formally approved in the United States for the treatment of panic attacks, major depression, post¬traumatic stress disorder, social anxiety, generalized anxiety disorder, panic disorder and obsessive-compulsive disorder. Paroxetine has a well-established safety profile and it shares the common side effects and contraindications of other SSRI's which include nausea and somnolence and is associated with weight gain.

This study proposes to conduct a retrospective cohort study to assess the risk of new onset diabetes among patients undergoing treatment with Pravastatin or other statins, and Paroxetine or other SSRI's. This study will compare the risk of co administration of two drug classes versus the use of each agent alone. In addition, the risk among patients prescribed Paroxetine and fibrates in combination, relative to the use of Paroxetine singly, will be examined to determine whether any interaction found between Paroxetine and statins extends to other drugs indicated for hypercholesterolemia.

The first primary objective of the study is to estimate the incidence of Type 2 Diabetes (T2DM) among patients newly exposed to pravastatin in combination with paroxetine, or other SSRIs, compared to those newly exposed to pravastatin alone. The second primary objective is to estimate the incidence of Type 2 Diabetes (T2DM) among patients newly exposed to paroxetine in combination with pravastatin, other statins, or fibrates, compared to those newly exposed to paroxetine alone.

Conditions

• Depression, Postpartum

Interventions

DRUG

Pravastatin alone

Pravastatin is a member of the drug class of statins, also known as HMG-CoA reductase inhibitors, and is known to reduce the amount of cholesterol and other fatty substances in the blood. In addition, pravastatin is indicated to reduce the risk of myocardial infarction, revascularization and cardiovascular mortality in hypercholesterolemic patients who do not have clinically apparent coronary heart disease.

DRUG

Paroxetine alone

Paroxetine is an orally administered selective serotonin reuptake inhibitor (SSRI) for the treatment of depression

DRUG

Pravastatin and paroxetine combined

Pravastatin is a member of the drug class of statins, also known as HMG-CoA reductase inhibitors, and is known to reduce the amount of cholesterol and other fatty substances in the blood. In addition, pravastatin is indicated to reduce the risk of myocardial infarction, revascularization and cardiovascular mortality in hypercholesterolemic patients who do not have clinically apparent coronary heart disease. Paroxetine is an orally administered selective serotonin reuptake inhibitor (SSRI) for the treatment of depression

Sponsors & Collaborators

• GlaxoSmithKline

  lead INDUSTRY

Principal Investigators

• GSK Clinical Trials · GlaxoSmithKline

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-12-31

Primary Completion

2012-05-31

Completion

2012-05-31