EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, July 12, 2004
To contact Susan L. Norris, M.D., M.P.H., call Mary Key Sones at 770/488-5131.

MEDICATION CAN HELP DIABETICS LOSE WEIGHT, BUT LONG-TERM EFFECTS UNCERTAIN

CHICAGO—An antidepressant drug and two medications for weight loss can help patients with diabetes achieve statistically significant weight loss over 26 to 52 weeks. But the magnitude of weight loss was modest, and the long-term health benefits and safety remain unclear, according to an article in the July 12 issue of the Archives of Internal Medicine, one of the JAMA/Archives journals.

According to information in the article, the prevalence of obesity in the United States increased from 12 percent in 1991 to 18 percent in 1998. Recent survey data indicate that 65 percent of Americans are overweight. The prevalence of diabetes mellitus is also rising, with an increase of 49 percent between 1990 and 2000. Among U.S. adults, 8.6 percent of those older than 20 have diabetes, one third of whom are undiagnosed. Obesity is closely related to type 2 diabetes, and weight reduction is an important part of the care delivered to obese people with diabetes.

Susan L. Norris, M.D., M.P.H., of the Centers for Disease Control and Prevention, Atlanta, Ga., and colleagues performed a meta-analysis to assess the efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes. A systematic review of the literature found sufficient data for the meta-analysis for the antidepressant drug fluoxetine and the weight loss medications orlistat and sibutramine. Fourteen randomized, placebo-controlled trials were included in the review, with a total of 2,231 patients.

"This meta-analysis provides evidence that fluoxetine, orlistat, and sibutramine can achieve modest but statistically significant short-term weight loss when used as a primary weight loss strategy," the authors report.

Fluoxetine produced weight reduction of 3.4 kilograms at eight to 16 weeks of follow-up; 5.1 kilograms at 24 to 30 weeks; and 5.8 kilograms at 52 weeks. Orlistat produced weight loss of 2.6 kilograms at 52 weeks. Sibutramine produced weight loss of 4.5 kilograms at up to 26 weeks.

Levels of glycated hemoglobin (measured by blood tests), which reflects overall control of diabetes and blood glucose levels, were also modestly reduced by fluoxetine (one percent at 8-16 weeks; one percent at 24 to 30 weeks; 1.8 percent at 52 weeks), orlistat (0.4 percent), and sibutramine (0.7 percent).

The three drugs were generally well tolerated and produced a low incidence of serious adverse events.

But the authors caution, "Since treatment duration was up to 52 weeks for fluoxetine and orlistat and 26 weeks for sibutramine, the long-term effects of these drugs on weight and health outcomes in persons with type two diabetes remain uncertain."

"Further work is needed to examine whether the combination of lifestyle modification and pharmacotherapy improves the efficacy of drug therapy, whether such combinations are synergistic or additive, and what dosage schedules and sequencing of the two interventions are optimal," they suggest. "The incidence of adverse events must be carefully monitored over the long term in diabetic populations, which already have multiple risk factors for major cardiovascular and neurologic events."

EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, July 12, 2004
To contact corresponding author Harlan M. Krumholz, M.D., call Karen Peart at 203/432-1326. To contact editorialist Kanu Chatterjee, M.B., F.R.C.P., call Kim Wong at 415/476-2557.

BETA-BLOCKER DRUGS WELL TOLERATED FOR HEART FAILURE PATIENTS

CHICAGO—Beta-blocker therapy in patients with heart failure is well tolerated and associated with fewer overall withdrawals and less heart failure deterioration than placebo, according to an article in the July 12 issue of the Archives of Internal Medicine, one of the JAMA/Archives journals.

Beta-blockers are a class of drugs that block beta-adrenergic substances, help relieve stress on the heart, slow the heart beat, lessen the force with which the heart muscle contracts, and reduce blood vessel contraction in the heart, brain, and throughout the body. According to information in the article, beta-blockers substantially improve survival in patients with chronic heart failure (HF) with left ventricular systolic dysfunction (failure of the left ventricle to contract strongly enough to pump blood out to the body). But concerns about cardiovascular adverse effects may deter physicians from prescribing this therapy.

Dennis T. Ko, M.D., of the University of Toronto, Ontario, Harlan Krumholz, M.D., of Yale University School of Medicine, and colleagues performed an overview of randomized trials comparing beta-blockers with placebo in patients with HF to quantify the risks of adverse effects. Trials were identified by electronic searches of the MEDLINE database from 1966 to 2002. Nine trials involving 14,594 patients with follow-up periods ranging from six to 24 months were included in the overview.

"Although beta-blocker therapy was associated with hypotension [low blood pressure], dizziness, and bradycardia [slow heart beat], the absolute increases in risk were small, and overall fewer patients were withdrawn from beta-blocker therapy than from placebo," the authors write.

Beta-blocker therapy was associated with a significant 27 percent relative reduction in all-cause mortality and absolute risk reduction of 34 deaths per 1,000 patients per year. It was associated with significant absolute annual increases in risks of hypotension (11 per 1,000), dizziness (57 per 1,000), and bradycardia (38 per 1,000). It was associated with a reduction in all-cause withdrawal of medication (14 per 1,000), HF hospitalizations (40 per 1,000), and worsening HF (52 per 1,000).

"The principal finding of our quantitative overview is that despite concerns about adverse effects, fewer patients with HF assigned to receive beta-blockers were withdrawn from therapy than were those assigned to receive placebo," the authors write. "This difference was primarily owing to a reduction of worsening HF associated with beta-blocker therapy."

EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, July 12, 2004
To contact Edward Lin, D.O., call Cindy Sanders at 404/686-8538.

APPETITE-STIMULATING HORMONE LEVELS DECREASE AFTER GASTRIC BYPASS SURGERY

CHICAGO—Severely obese patients who undergo gastric bypass surgery show significant early declines in levels of a hormone that stimulates the appetite. This may possibly explain, in part, the loss of hunger sensation and rapid weight loss observed following gastric bypass, according to an article in the July issue of the Archives of Surgery, one of the JAMA/Archives journals.

According to information in the article, the hormone ghrelin is a circulating appetite stimulant produced primarily in the stomach. It plays a presumed role in regulating body weight. Circulating ghrelin levels significantly increase before a meal and rapidly decline after eating, implicating this hormone as a principal signal of hunger and meal initiation.

Edward Lin, D.O., and colleagues at Emory University, Atlanta, conducted a study to determine if early alternations in ghrelin levels in severely obese patients undergoing weight reduction surgery may be attributed to gastric partitioning. The study included 42 patients who were morbidly obese, with a body mass index (BMI) of 40 or higher, and six lean control patients. (BMI is calculated as weight in kilograms divided by the square of height in meters.)

Thirty-four patients underwent Roux-en-Y gastric bypass (RYGB), a procedure in which the stomach is divided to create a pouch out of the smaller proximal (near) portion of the stomach, and then attached to the small intestine, bypassing a large part of the stomach and all of the duodenum. Eight patients underwent other gastric procedures that did not involve complete division of the stomach. Six non-obese patients undergoing anti-reflux surgery served as lean controls. The researchers measured ghrelin levels in blood plasma samples at different stages of surgical intervention.

"A divided gastroplasty creating a small proximal gastric pouch results in significant early declines in circulating ghrelin levels that are not observed with other gastric procedures," they report.

Among the patients undergoing gastric bypass, preoperative mean levels of ghrelin were 355 picograms per milliliter (plus or minus 20), compared with postoperative levels of 246 picograms per milliliter (plus or minus 13). Ghrelin levels were not significantly changed in severely obese patients undergoing other gastric procedures, or in lean controls. Compared with the morbidly obese subjects, the lean controls had significantly higher plasma ghrelin levels at baseline.

"This study demonstrates that complete division of the stomach, forming a small vertical pouch, contributes to the decline in circulating ghrelin levels," the authors write. "It further supports that the decline in ghrelin levels following RYGB surgery is not a gradual process, but occurs early following the procedure."

The authors believe this is the first human study to demonstrate a reduction in circulating ghrelin early following division of the stomach during RYGB surgery.

EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, July 12, 2004
To contact Albert Alm, M.D., email: Albert.Alm{at}adademiska.se.

LATANOPROST SAFE AND WELL TOLERATED FOR GLAUCOMA TREATMENT

CHICAGO—The drug latanoprost is safe and well tolerated as adjunctive therapy for long-term treatment of the most common form of glaucoma, according to an article in the July issue of the Archives of Ophthalmology, one of the JAMA/Archives journals.

Glaucoma is a condition in which the pressure inside the eyes rises. If untreated, glaucoma may damage the optic nerve and other parts of the eye, and my lead to blindness. According to information in the article, latanoprost is a derivative of the chemical prostaglandin F2-alpha. Prostaglandin derivatives have been shown to help lower intraocular pressure (IOP).

Albert Alm, M.D., of University Hospital, Uppsala, Sweden, and colleagues evaluated the safety and efficacy of 0.005 percent latanoprost administered once daily for five years as adjunctive therapy to other IOP-lowering drugs in patients whose IOP was uncontrolled with a single form of therapy. Patients with primary open-angle glaucoma (the most common form of glaucoma in the West) or exfoliation glaucoma (a form of glaucoma in which abnormal deposits are found on the surface of the lens and on other structures inside the eyeball) who completed a three-year, open-label, uncontrolled prospective trial could enter a two-year extension phase.

Among 519 patients enrolled in the original three-year study, 380 enrolled in the extension phase. The researchers examined the incidence and progression of increased iris pigmentation among the patients, assessed from high-resolution color photographs taken at baseline and at 14 subsequent visits. IOP and adverse events were also recorded.

"In all, 127 (33.4 percent) of 380 patients who continued in the extension phase had developed increased iris pigmentation in one or both eyes after five years of adjunctive therapy with 0.005 percent latanoprost," the authors write. "In particular, more than three quarters of the patients with either green-brown or yellow-brown eyes were affected."

For those who developed iris pigmentation, onset occurred during the first eight months in 74 percent and during the first 24 months in 94 percent.

The researchers also evaluated the long-term efficacy of latanoprost in lowering IOP when administered as adjunctive therapy. "The overall mean intraocular pressure reduction from baseline of 25 percent was sustained with no need for change in intraocular pressure-lowering treatment in 70 percent of the eyes," they report.

Almost all ocular and systemic adverse events were mild in intensity. These included visual field defect (a blind spot or blind area within the normal bounds of vision), eye irritation, cataract (clouding of the lens portion of the eye), and eye abnormality.

EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, July 12, 2004
To contact David S. Friedman, M.D., M.P.H., call John Lazarou at 410/502-8902.

AFRICAN AMERICAN NURSING HOME RESIDENTS MORE LIKELY THAN WHITE RESIDENTS TO HAVE VISION LOSS DUE TO CATARACT

CHICAGO—Cataract was the primary cause of low vision in 54 percent of African American nursing home residents compared to 37 percent of white residents, according to an article in the July issue of the Archives of Ophthalmology, one of the JAMA/Archives journals.

According to background information in the article, blindness and visual impairment rates increase with age, and are also higher among nursing home residents.

David S. Friedman, M.D., M.P.H., of the Wilmer Eye Institute, The Johns Hopkins University, Baltimore, and colleagues measured the vision of 1,307 nursing home residents (304 African Americans, 997 white residents) in 28 nursing homes in Maryland and Delaware. Residents with visual acuity worse than 20/40 in their better-seeing eye (N = 412) were also examined by an ophthalmologist to determine the main cause for reduced vision.

Cataract was the leading cause of low vision in both African American and white residents (54 percent and 37 percent, respectively), and was a more common cause of vision loss among African American patients (24.2 percent) than white patients (11.8 percent). Macular degeneration caused low vision in 29 percent of white residents and 7 percent in African American patients. In four percent of white residents and ten percent of African American residents, glaucoma caused low vision.

"The higher prevalence of cataract among African American persons can be attributed to any of several factors. Previous research...indicates that African American persons are less likely to visit an ophthalmologist, and they obtain cataract surgery at lower rates than white persons," the authors write.