1 Boring Old Man

3 Schizophrenia Drugs May Raise Diabetes Risk, Study Says
New York Times
By ERICA GOODE
August 25, 2003

^{Three drugs commonly prescribed for schizophrenia and other psychotic illnesses increased patients’ risk of developing diabetes when compared with older antipsychotic medications, researchers said yesterday, presenting the results from a long-awaited study of patients treated at veterans hospitals and clinics across the country.}

^{The drugs — Zyprexa, made by Eli Lilly, Risperdal, made by Jannsen Pharmaceutica, and Seroquel, made by AstraZeneca — were associated with higher rates of diabetes than older generation drugs for schizophrenia like Haldol, the study found. But the increased risk was statistically significant only for Zyprexa and Risperdal, the researchers said, possibly because of the smaller number of subjects who took Seroquel…}

SEROQUEL® and Diabetes: What We Know
• In clinical trials, SEROQUEL has shown no difference in mean change of random glucose measurements compared to either placebo or other antipsychotics.
• In patients taking SEROQUEL, post-marketing reports of diabetes or diabetes-related events are very rare [<0.01%]. These reports were confounded by pre-existing or co-existing risk factors and/or had limited information.
• The results of retrospective epidemiology studies of SEROQUEL and diabetes have been inconsistent and inconclusive.
• Many patients with psychiatric illness have other characteristics that may contribute to metabolic abnormalities.

Factor	Schizophrenia %	Bipolar Disorder %	General Population %
Smoking	73	35-55	25
Obesity	18	30	33
Diabetes	13	26	7.0

A survey of reports of quetiapine-associated hyperglycemia and diabetes mellitus
J Clin Psychiatry. 2004 Jun;65(6):857-63.
by Koller EA, Weber J, Doraiswamy PM, Schneider BS
^{Division of Metabolic and Endocrine Drug Products
Center for Drug Evaluation and Review
US Food and Drug Administration, Rockville, MD, USA.}

^Abstract

^{OBJECTIVE: To explore the clinical characteristics of hyperglycemia in patients treated with quetiapine.}

^{METHOD: A pharmacovigilance survey of spontaneously reported adverse events in quetiapine-treated patients was conducted using reports from the U.S. Food and Drug Administration MedWatch program (January 1, 1997, through July 31, 2002) and published cases using the search terms hyperglycemia, diabetes, acidosis, ketosis, and ketoacidosis.}

^{RESULTS: We identified 46 reports of quetiapine-associated hyperglycemia or diabetes and 9 additional reports of acidosis that occurred in the absence of hyperglycemia and were excluded from the immediate analyses. Of the reports of quetiapine-associated hyperglycemia, 34 patients had newly diagnosed hyperglycemia, 8 had exacerbation of preexisting diabetes mellitus, and 4 could not be classified. The mean +/- SD age was 35.3 +/- 16.2 years (range, 5-76 years). New-onset patients (aged 31.2 +/- 14.8 years) tended to be younger than those with preexisting diabetes (43.5 +/- 16.4 years, p = .08). The overall male:female ratio was 1.9. Most cases appeared within 6 months of quetiapine initiation. The severity of cases ranged from mild glucose intolerance to diabetic ketoacidosis or hyperosmolar coma. There were 21 cases of ketoacidosis or ketosis. There were 11 deaths.}

^{CONCLUSION: Atypical antipsychotic use may unmask or precipitate hyperglycemia. UPDATE: An additional 23 cases were identified since August 1, 2002, the end of the first survey, by extending the search through November 30, 2003, bringing the total to 69.}

^{January 30, 2004}

^{Dear Healthcare Provider,
AstraZeneca Pharmaceuticals LP would like to inform you of important labeling changes regarding SEROQUEL® [quetiapine fumarate]. The FDA has asked all manufacturers of atypical antipsychotics, including AstraZeneca, to add a Warnings statement descibing the increased risk of hyperglycemia and diabetes in patients taking these medications, including SEROQUEL. Accordingly, the SEROQUEL Prescribing Information has been updated with the addition of the following information: etc…}

^{Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics, including Seroquel. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics. Precise risk estimates for hyperglycemia-related adverse events in patients treated with atypical antipsychotics are not available…}

^{Weight Gain: In schizophrenia trials the proportions of patients meeting a weight gain criterion of >7% of body weight were compared in a pool of four 3- to 6-week placebo-controlled clinical trials, revealing a statistically significantly greater incidence of weight gain for SEROQUEL (23%) compared to placebo (6%). In mania monotherapy trials the proportions of patients meeting the same weight gain criterion were 21% compared to 7% for placebo and in mania adjunct trials the proportion of patients meeting the same weight criterion were 13% compared to 4% for placebo…}

^Team

^{We are really on a roll.}

^{Enjoy the standalone – those of you attending.}

^{I know you are all working flat out – but I can tell you that SET , and everyone in AZ, really appreciates the work you are doing and the impact you are having.}

^{Keep driving the brand……………..I never thought that I could say Seroquel is AstraZeneca’s major megabrand….Now I can….}

^{Thanks for what you are doing.}

^geoff

Astra Settles Claims Related to Seroquel
Wall Street Journal
By SIMON ZEKARIA
AUGUST 10, 2010

^{LONDON — AstraZeneca PLC said Monday it has reached a $198 million settlement over claims in the U.S. regarding its best-selling antipsychotic drug Seroquel. The U.K. pharmaceutical company has faced thousands of product-liability lawsuits alleging that the use of Seroquel caused diabetes and other injuries, and that the company failed to adequately warn of the drug’s risks.}

^{The company has also faced long-running allegations it improperly promoted the drug, which is approved to treat schizophrenia, bipolar disorder and depression. The settlement relates to 17,500 product-liability claims, and the company said the mediation process over claims is continuing in both federal and state jurisdictions. "We remain committed to a strong defense effort, but will also continue to participate in good faith in court-ordered mediation," AstraZeneca said Monday in a statement…}

AstraZeneca Said to Pay $150 Million to Settle Seroquel Suits
Bloomberg Business Week
By Jef Feeley
February 17, 2011

^{AstraZeneca Plc agreed to pay $150 million to settle more lawsuits claiming its antipsychotic drug Seroquel causes diabetes, pushing the amount the drugmaker has paid to resolve cases over the medicine to almost $350 million, people familiar with the accords said. AstraZeneca, the U.K.’s second-biggest drugmaker, will resolve about 6,000 cases alleging the company knew Seroquel could cause diabetes and failed to adequately warn patients, two people familiar with the settlements said. They spoke on the condition of anonymity because they weren’t authorized to speak publicly about the accords. The cases settled for an average of about $25,000, the people said.}

^{The settlements signal AstraZeneca is seeking to put the Seroquel litigation behind it as it works to overcome setbacks in its drug-development pipeline, said Jeremy Batstone-Carr, London-based analyst for Charles Stanley & Co., who rates the drugmaker’s shares as “accumulate.” “Legal cases represent one of the great imponderables that can act on shareholder sentiment,” Batstone-Carr said. “You try to clear the decks and get investors as great a degree of certainty as possible.”}

^{The settlement, which resulted from a court-ordered mediation, leaves AstraZeneca now facing only about 4,000 Seroquel claims, the people said. The London-based drugmaker announced last summer it had resolved about two-thirds of the 26,000 suits over the drug that had been filed in courts around the U.S…}