Orlistat use in type 2 diabetes

OBJECTIVE: To review the use of orlistat in type 2 diabetes. DATA SOURCES: A MEDLINE search of the English-language literature (1990-August 2001) was performed using the key terms orlistat, obesity, glucose, and diabetes. DATA EXTRACTION: All articles pertaining to orlistat were considered for inclusion, with emphasis placed on randomized, placebo-controlled, double-blind clinical trials. DATA SYNTHESIS: In April 1999, orlistat was approved by the Food and Drug Administration for the treatment of obesity. Of 13 randomized, placebo-controlled studies, only 2 reported specific data in individuals with type 2 diabetes. Both reported significant weight reduction and improved glycemic control over placebo. CONCLUSIONS: Since weight loss is a difficult goal to achieve in patients with type 2 diabetes, orlistat can be a safe, effective addition to a multidisciplinary approach.     

Chromium treatment has no effect in patients with poorly controlled, insulin-treated type 2 diabetes in an obese Western population: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: Chromium treatment has been reported to improve glycemic control and insulin sensitivity in specific populations of patients with type 2 diabetes. The aim of this study was to determine the effect of chromium treatment on glycemic control in a Western population of insulin-dependent patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this 6-month double-blind study, patients with an HbA(1c) (A1C) >8% and insulin requirements of >50 units/day were randomly assigned to receive treatment with placebo or 500 or 1,000 mug chromium daily in the form of chromium picolinate. The primary efficacy parameter was a change in A1C. Secondary end points were changes in lipid profile, BMI, blood pressure, and insulin requirements. RESULTS: In this per-protocol analysis (n = 46), the decrease in A1C was approximately equal across the three groups (0.4%). All patients had a BMI >25 kg/m(2). No differences were found in the secondary end points. We found a weak relationship between an increasing serum chromium concentration and improvement of the lipid profile. CONCLUSIONS: There is no evidence that high-dose chromium treatment is effective in obese Western patients with type 2 diabetes.     

Insulin glargine: a new basal insulin

OBJECTIVE: To review the pharmacology, pharmacokinetics, dosing guidelines, adverse effects, drug interactions, and clinical efficacy of insulin glargine. DATA SOURCES: Primary and review articles regarding insulin glargine were identified by MEDLINE search (1966-July 2001); abstracts were identified through Institute for Scientific Information Web of Science (1995-July 2001) and the American Diabetes Association. Additional information was obtained from the insulin glargine product information. STUDY SELECTION AND DATA EXTRACTION: All of the articles and meeting abstracts identified from the data sources were evaluated, and all information deemed relevant was included in this review. Priority was placed on data from the primary medical literature. DATA SYNTHESIS: Insulin glargine is a long-acting, recombinant human insulin analog that is given once daily as a basal source of insulin in patients with type 1 or type 2 diabetes mellitus. Modification of the basic insulin structure has produced a new insulin that is soluble at an acidic pH, but precipitates in the subcutaneous tissue and is slowly released from a depot. Insulin glargine has a slower onset of action than NPH insulin and a longer duration of action with no peak activity. Once-daily administration of insulin glargine has comparable efficacy to that of NPH insulin administered once or twice daily in basal-bolus regimens when used in combination with intermittent doses of regular insulin or insulin lispro in patients with type 1 and type 2 diabetes, and in conjunction with oral antidiabetic agents in patients with type 2 diabetes. Overall, insulin glargine has an incidence of hypoglycemia comparable to or less than that of NPH insulin, with a reduced incidence of nocturnal hypoglycemia compared with NPH insulin seen in some studies. CONCLUSIONS: Insulin glargine is a long-acting insulin analog capable of providing 24-hour basal insulin coverage when administered once daily at bedtime. Its activity profile, which lacks a pronounced peak, more closely resembles that of endogenous basal insulin than that of other intermediate- or long-acting insulins and appears more likely to be associated with a reduced incidence of hypoglycemia, particularly nocturnal hypoglycemia. Insulin glargine physiologically provides basal insulin but, for most patients, the addition of a rapid-acting insulin, like insulin lispro, before or with meals will need to be included in the treatment regimen to achieve optimal management of blood glucose concentrations.     

Efalizumab for the treatment of moderate to severe plaque psoriasis

OBJECTIVE: To review the pharmacology, efficacy, and safety of efalizumab for the treatment of moderate to severe plaque psoriasis. DATA SOURCES: A MEDLINE search (1966-May 2005) using the key words hu1124, anti-CD11a, efalizumab, Raptiva, Xanelim, and psoriasis was conducted. References of identified articles were reviewed for additional citations. STUDY SELECTION AND DATA EXTRACTION: Clinical trials evaluating the pharmacology, efficacy, and safety of efalizumab for treatment of moderate to severe plaque psoriasis in adults were included in our review. DATA SYNTHESIS: Efalizumab's ability to inhibit the binding of CD11a, a subunit of leukocyte function-associated antigen type 1, to intracellular adhesion molecule 1 results in decreased T-cell activation and migration, 2 key steps in the immunopathogenesis of psoriasis. Results of clinical trials have demonstrated that efalizumab administered subcutaneously is a safe and effective treatment for moderate to severe plaque psoriasis. Efalizumab was well tolerated in trials, with the majority of adverse events arising with the first dose and decreasing with subsequent doses. The high cost of this agent and lack of head-to-head trials with other drugs will likely restrict its use to patients who have failed prior systemic therapy or phototherapy. CONCLUSIONS: Efalizumab is a safe and effective therapy for treatment of moderate to severe plaque psoriasis in patients who have failed prior systemic therapy or phototherapy.     

The 'forgotten' bile acid sequestrants: is now a good time to remember?

Over 30 years ago, bile acid sequestrants (BAS) were among the first drugs approved to lower cholesterol levels. For over 10 years, BAS have been known to reduce glucose levels. Most importantly, BAS have been shown in outcomes studies to reduce cardiovascular events. Because they are true nonsystemic agents, BAS are generally safe and not associated with serious systemic adverse experiences. Despite their proven atherosclerotic coronary heart disease (CHD) benefits, and irrespective of their favorable effects on major CHD risk factors (hypercholesterolemia and hyperglycemia), BAS are not among the more frequently used drug treatments for hypercholesterolemia, even in patients with type 2 diabetes mellitus. Recent "high-profile" findings of investigational and approved lipid-altering and antidiabetes drug therapies illustrate that drug-induced improvements in lipid and glucose levels do not always reduce CHD risk. It may therefore be time to reconsider the clinical use of BAS. This review focuses on the recent lessons learned, and the potential mechanisms involved in efficacy and safety issues raised with torcetrapib and rosiglitazone with analogies related to the use of BAS therapy. Known and proposed mechanisms of how BAS may improve lipid and glucose levels are discussed, which are effects that may help explain how BAS reduce CHD risk. Improved tolerability of newer BAS (eg, colesevelam hydrochloride) and a "new" appreciation of the historic benefits of these "old" therapeutic agents may lead to an increased treatment role for these drugs, particularly in hypercholesterolemic patients with type 2 diabetes mellitus.     

Pharmacotherapy of type 2 diabetes mellitus

OBJECTIVE: To review the drug treatments and some of the popular, nontraditional remedies now available for type 2 diabetes mellitus, as well as selected investigational agents; to describe each medication's place in the overall approach to treatment. DATA SOURCES: English-language journals, abstracts, review articles, and newspaper accounts. DATA SYNTHESIS: In the past five years, there has been tremendous progress in the pharmacotherapy of diabetes, particularly type 2 diabetes. Several new agents have entered the clinical arena, and many more are in the late stages of investigation leading to approval. Sulfonylureas stimulate the production and release of insulin; these drugs must be used in patients with an intact pancreas. The meglitinides are nonsulfonylurea agents that are also insulin secretagogues. Unlike the sulfonylureas, repaglinide appears to require the presence of glucose to close the adenosine triphosphate-sensitive potassium channels and induce calcium influx. Metformin reduces hepatic glucose production in some patients and increases peripheral glucose utilization, but its use is hampered by a high percentage of adverse reactions. Disaccharidase inhibitors effectively compensate for the defective early-phase insulin release by slowing the production of sugars from carbohydrates. Thiazolidinediones appear to activate peroxisome proliferator-activated receptor gamma, which is involved in the metabolism of lipids. Short-acting insulin and the role of weight-loss agents are also discussed. CONCLUSIONS: The availability of new options for diabetes therapy provides a chance for successful therapy in a larger number of patients. However, it is important to consider how much true benefit these new forms of treatment will have on the diabetic community. The best choice for a patient remains controversial.     

Inhaled insulin: Exubera

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of Exubera, a novel, dry-powder formulation of insulin for inhalation, and describe patient satisfaction and quality-of-life data. DATA SOURCES: A MEDLINE search (1966-November 2004) was conducted using the key words inhaled insulin and Exubera for clinical trials limited to human research published in English. BIOSIS Previews and the American Diabetes Association Scientific Abstracts were used for published abstract information. STUDY SELECTION AND DATA EXTRACTION: All available human studies of Exubera were selected for review. References of identified articles were used for additional citations. DATA SYNTHESIS: Exubera is a rapid-acting insulin administered by oral inhalation before meals with long-acting insulin administered subcutaneously once or twice daily for type 1 or 2 diabetes mellitus. Exubera provides similar efficacy and improved patient satisfaction compared with standard subcutaneous insulin therapy (ie, NPH twice daily with regular insulin before meals). Efficacy has also been demonstrated for Exubera when used as adjunctive therapy with oral medications for type 2 diabetes. The onset of Exubera is more rapid and its duration of action is similar to that of regular insulin. To date, Exubera administered before meals with a once-daily long-acting subcutaneous insulin (usually Ultralente) has been compared with standard subcutaneous NPH/regular insulin regimens. Comparison of premeal Exubera plus a basal long-acting insulin analog (eg, glargine) with a regimen of premeal subcutaneous rapid-acting insulin analog (eg, lispro or aspart) plus a basal long-acting insulin analog (eg, glargine) is needed to fully evaluate Exubera. Pulmonary safety appears to be maintained for up to 4 years, although there are no data, as of this writing, on the use of this agent in patients with pulmonary conditions. CONCLUSIONS: Exubera is an effective inhaled insulin for preprandial use in type 1 or 2 diabetes. Improved patient satisfaction over injected insulin increases its potential for use earlier in the treatment of type 2 diabetes.     

Systematic review of herbs and dietary supplements for glycemic control in diabetes

OBJECTIVE: To conduct a systematic review of the published literature on the efficacy and safety of herbal therapies and vitamin/mineral supplements for glucose control in patients with diabetes. RESEARCH DESIGN AND METHODS: We conducted an electronic literature search of MEDLINE, OLDMEDLINE, Cochrane Library Database, and HealthSTAR, from database inception to May 2002, in addition to performing hand searches and consulting with experts in the field. Available clinical studies published in the English language that used human participants and examined glycemic control were included. Data were extracted in a standardized manner, and two independent investigators assessed methodological quality of randomized controlled trials using the Jadad scale. RESULTS: A total of 108 trials examining 36 herbs (single or in combination) and 9 vitamin/mineral supplements, involving 4,565 patients with diabetes or impaired glucose tolerance, met the inclusion criteria and were analyzed. There were 58 controlled clinical trials involving individuals with diabetes or impaired glucose tolerance (42 randomized and 16 nonrandomized trials). Most studies involved patients with type 2 diabetes. Heterogeneity and the small number of studies per supplement precluded formal meta-analyses. Of these 58 trials, the direction of the evidence for improved glucose control was positive in 76% (44 of 58). Very few adverse effects were reported. CONCLUSIONS: There is still insufficient evidence to draw definitive conclusions about the efficacy of individual herbs and supplements for diabetes; however, they appear to be generally safe. The available data suggest that several supplements may warrant further study. The best evidence for efficacy from adequately designed randomized controlled trials (RCTs) is available for Coccinia indica and American ginseng. Chromium has been the most widely studied supplement. Other supplements with positive preliminary results include Gymnema sylvestre, Aloe vera, vanadium, Momordica charantia, and nopal.     

Insulin detemir--a new basal insulin analog

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trial data, adverse effects, and role in therapy of insulin detemir. DATA SOURCES: Articles and meeting abstracts were identified through searches of MEDLINE (1996-June 2004), EMBASE (1980-June 2004), and International Pharmaceutical Abstracts (1970-June 2004) databases, and unpublished information was provided by the manufacturer. STUDY SELECTION AND DATA EXTRACTION: All available studies relating to insulin detemir's pharmacology were selected. Only human studies were used for pharmacokinetic, drug interaction, efficacy, and safety data. DATA SYNTHESIS: Insulin detemir is a basal insulin analog that has been shown to improve glycemic control in patients with type 1 and type 2 diabetes. CONCLUSIONS: Insulin detemir offers some benefits over NPH for use as basal insulin in patients with type 1 and type 2 diabetes.     

Pharmacologic prevention or delay of type 2 diabetes mellitus

OBJECTIVE: To evaluate the current data on pharmacologic interventions intended to prevent or delay the onset of type 2 diabetes mellitus. DATA SOURCES: Searches of MEDLINE (1966-July 2002) and an extensive manual review of journals were performed using the key search terms diabetes mellitus, metformin, acarbose, troglitazone, orlistat, nateglinide, risk reduction, and prevention. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated, and all information deemed relevant was included for this review. Randomized controlled trials and meta-analyses were included if the primary outcome measure was prevention of diabetes and/or change in the rate of progression to diabetes. DATA SYNTHESIS: Type 2 diabetes mellitus is a growing epidemic. Major risk factors include obesity, impaired glucose tolerance, and impaired fasting glucose. Complications of diabetes result in significant morbidity and mortality and are a substantial public health issue. Four randomized, blinded, controlled trials have assessed the efficacy of different medications, including metformin, troglitazone, acarbose, and orlistat, at decreasing the risk of progression to diabetes in patients at risk for developing diabetes. All of these agents decreased the risk of progression to diabetes. CONCLUSIONS: Metformin, troglitazone, acarbose, and orlistat have been shown to decrease the risk of progression to diabetes in patients at risk for developing diabetes. Other questions that address issues such as identifying target populations, cost-effectiveness, and screening strategies must be answered to more fully define the place of pharmacologic therapy to prevent or delay diabetes.     

Incretin mimetics as emerging treatments for type 2 diabetes

OBJECTIVE: To review the physiology, pharmacology, and clinical efficacy of glucagon-like peptide (GLP-1) and the incretin mimetics exenatide and liraglutide in clinical studies. DATA SOURCES: Primary literature obtained via MEDLINE (1966-April 2004) and International Pharmaceutical Abstracts (1970-April 2004) searches; abstracts obtained from meeting sources and manufacturers. STUDY SELECTION AND DATA EXTRACTION: All English-language studies and abstracts evaluating GLP-1, exenatide, and liraglutide in the treatment of patients with type 2 diabetes were reviewed. Data from animal studies were also included if human data were not available. Primary and review articles related to the physiology, development, and evaluation of GLP-1s were reviewed. DATA SYNTHESIS: GLP-1, exenatide (exendin-4, AC2993), and liraglutide (NN2211) are incretin mimetics that have been shown in human studies to be an effective treatment to improve glycemic control in patients with type 2 diabetes. Mechanisms by which these compounds improve glycemic control include enhancing glucose-dependent pancreatic secretion of insulin in response to nutrient intake, inhibiting glucagon secretion, delaying gastric emptying, and promoting early satiety. GLP-1 has been shown to promote pancreatic progenitor cell differentiation and improve beta-cell function and lifespan. Reported adverse effects of exenatide and liraglutide include nausea, vomiting, and transient headache, as well as increased risk of hypoglycemia when used with sulfonylureas. CONCLUSIONS: Clinical studies show that GLP-1, exenatide, and liraglutide improve glycemic control for patients with type 2 diabetes through unique mechanisms not available with current pharmaceutical products. Ongoing Phase III studies will help to further position these compounds as treatment options for patients with type 2 diabetes.     

Sitagliptin: a dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes

OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of sitagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor in the management of type 2 diabetes mellitus. DATA SOURCES: A MEDLINE search (1966-February 2006) was conducted for English-language articles using the terms dipeptidyl peptidase IV inhibitor, incretin, MK-0431, and sitagliptin. Abstracts from the American Diabetes Association annual meetings in 2004 and 2005 were included as sources of data. STUDY SELECTION AND DATA EXTRACTION: Articles pertaining to the pharmacology of sitagliptin, its pharmacokinetics, safety and efficacy were reviewed. DATA SYNTHESIS: Sitagliptin is a potent, competitive, reversible inhibitor of the DPP-IV enzyme. It is eliminated renally, with a terminal half-life of 11.8-14.4 hours. In Phase II clinical trials, sitagliptin was found to be superior to placebo for the treatment of type 2 diabetes mellitus. Results of a small trial comparing sitagliptin with glipizide indicate that both treatments are comparable. The efficacy of sitagliptin has also been demonstrated when used as adjunctive therapy with metformin. Few adverse effects have been reported. Weight gain and hypoglycemia have not been seen with sitagliptin therapy. CONCLUSIONS: Based on its unique mechanism of action, sitagliptin will provide practitioners with an additional tool in the treatment of diabetes. Review of the literature to date implies sitagliptin may be effective as monotherapy in type 2 diabetes. In addition, existing evidence supports the use of sitagliptin as adjunct therapy to sulfonylureas and metformin. Another advantage of sitagliptin use is that it appears to be free from the adverse effects of weight gain and hypoglycemia that are associated with currently available treatments.     

Metformin for prevention of type 2 diabetes

OBJECTIVE: To evaluate evidence from the medical literature that metformin is effective in preventing type 2 diabetes. DATA SOURCES: Primary literature was accessed via a MEDLINE search (1966-December 2003) using the terms metformin, type 2 diabetes, and prevention. DATA SYNTHESIS: Two studies evaluated metformin's potential to prevent type 2 diabetes, finding that metformin maintained or reduced fasting blood glucose in non-diabetics. Recently, a large study by the Diabetes Prevention Program showed that metformin may reduce the incidence of diabetes. Researchers compared lifestyle changes, metformin therapy, and placebo groups. They found that both lifestyle changes (58%) and metformin therapy (31%) significantly reduced the occurrence of type 2 diabetes versus placebo. CONCLUSIONS: These studies provide evidence that metformin may reduce the occurrence of type 2 diabetes. Because long-term efficacy has not been determined, further studies are needed.     

Pramlintide for the treatment of diabetes mellitus

OBJECTIVE: To provide an overview of the role of amylin, as well as that of pramlintide, a synthetic analog of amylin, in maintaining glucose homeostasis; and discuss the pharmacology, pharmacokinetics, efficacy, adverse effects, and role of pramlintide in the control of postprandial hyperglycemia. DATA SOURCES: The data presented in this review were obtained from published literature, abstracts presented at scientific meetings, and information on file with the manufacturer. MEDLINE searches (1986-March 2003) using the search terms pramlintide and amylin were conducted to identify clinical trials and review articles. Additionally, the bibliographies of the identified articles were reviewed. DATA SYNTHESIS: Clinical trials have demonstrated that amylin in combination with insulin controls postprandial glucose levels by decreasing food intake, slowing gastric emptying, and suppressing glucagon secretion. Clinical trials also showed significant decreases in mean plasma glucose levels and glycosylated hemoglobin, as well as the added benefits of weight loss and reduction in insulin doses. The most commonly reported adverse effects associated with pramlintide in clinical trials were gastrointestinal complaints and hypoglycemia, which occurred most frequently during initiation of therapy. CONCLUSIONS: The administration of insulin alone often does not result in optimal metabolic control. The treatment of amylin deficiency, in addition to insulin deficiency, may be warranted in order to obtain glucose homeostasis. The role of pramlintide, an amylin analog, will become clearer as more clinical data become available.     

Role of risperidone in children with autism spectrum disorder

OBJECTIVE: To review the clinical trials investigating the efficacy and safety of risperidone in the treatment of children with autism spectrum disorder (ASD). DATA SOURCES: Searches of MEDLINE/PubMed (1992-February 2006) were conducted, as well as an extensive manual review of journals, using the key words autism and risperidone. STUDY SELECTION AND DATA EXTRACTION: Only double-blind, placebo-controlled trials were included for review. DATA SYNTHESIS: ASD is the most common of the pervasive developmental disorders. The main characteristics (core symptoms) of autism are impairment in social skills, problems communicating, and stereotypical movements. Behavioral manifestations or maladaptive behaviors include aggression, irritability, hyperactivity, inattention, impulsivity, tantrums, and self-injurious behavior. CONCLUSIONS: Based on the data examined, risperidone appears efficacious and safe for treating certain behavioral aspects of autism including irritability, aggression, hyperactivity, and stereotypy. It does not appear to be as effective for the treatment of the core symptoms of autism.     

Duloxetine: a dual reuptake inhibitor

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of duloxetine for the treatment of major depressive disorder (MDD). DATA SOURCES: Searches using MEDLINE and PsycINFO were conducted (1966 to November 2003). STUDY SELECTION AND DATA EXTRACTION: All duloxetine MDD information gathered was considered. Articles containing comprehensive information regarding duloxetine use for MDD were evaluated. DATA SYNTHESIS: Duloxetine is a serotonin-norepinephrine reuptake inhibitor being considered for treatment of MDD and stress urinary incontinence. While approved dosing ranges have not yet been determined, studies support the efficacy and safety of 40-60 mg twice daily for the treatment of acute MDD. Adverse effects have been of mild to moderate severity and are considered to be transient. Cardiovascular effects (increased heart rate or blood pressure), while present, do not appear to be clinically significant. Overall, duloxetine appears to be well tolerated. CONCLUSIONS: Duloxetine is a safe and effective antidepressant. Approval of this agent provides another treatment option for the management of MDD.     

Effect of glucosamine on glucose control

OBJECTIVE: To review the literature regarding the effect of glucosamine on glucose control. DATA SOURCES: English-language articles on the effects of administration of exogenous glucosamine on glucose control were identified through a search of MEDLINE (1966-March 2006), EMBASE (1988-March 2006), and International Pharmaceutical Abstracts (1970-March 2006) databases using the search terms glucosamine, blood glucose, and diabetes mellitus. Abstracts of articles were then reviewed to determine relevance to the topic. Bibliographies of selected articles were screened for other pertinent references. DATA SYNTHESIS: Theoretically, glucosamine may alter glucose metabolism. Insulin resistance has been noted following intravenous administration of glucosamine in animal studies; however, these findings have not been confirmed in humans. Alterations in glucose control have not been documented in long-term efficacy studies using oral glucosamine for osteoarthritis or in trials of short duration conducted in healthy or diabetic subjects. The long-term effects of glucosamine in patients with diabetes have yet to be established in well-controlled trials. CONCLUSIONS: Small, short-term studies suggest that glucosamine may be used in selected patients without affecting glucose control; however, data in patients with diabetes mellitus are limited, and close monitoring for potential changes in glucose control is recommended.     

Insulin strategies for type 2 diabetes mellitus

OBJECTIVE: To review the currently available insulin analogs and the benefits of insulin therapy in the treatment of type 2 diabetes mellitus. DATA SOURCES: A MEDLINE search (1990-March 2004) was conducted using insulin and type 2 diabetes mellitus as search terms to identify clinical trials and review articles. The bibliographies of identified articles were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and deemed relevant if they included and assessed clinical outcomes. DATA SYNTHESIS: Since its discovery in 1922, insulin therapy has been the only available pharmacologic treatment for type 1 diabetes and a mainstay therapy for patients with type 2 diabetes who fail to obtain glycemic control with oral antidiabetic agents. This article reviews the current insulin analogs available on the market and insulin regimens that are designed to mimic the pancreatic beta-cells' response to a glucose load. CONCLUSIONS: Insulin therapy is often withheld until late in the disease process for patients with type 2 diabetes mellitus. This results in an enormous burden of disease for patients. Insulin therapy is beneficial in obtaining glycemic control and may attenuate the complications associated with diabetes.     

Sincalide in patients with parenteral nutrition-associated gallbladder disease

OBJECTIVE: To review the role of sincalide in treating and preventing parenteral nutrition (PN)-associated gallbladder disease. DATA SOURCES: A MEDLINE (1996-March 2004) search was performed using the key terms cholecystokinin, sincalide, parenteral nutrition, cholelithiasis, cholestasis, and sludge. DATA SYNTHESIS: Five human studies investigated the safety and efficacy of sincalide in patients with PN-associated gallbladder disease. Sincalide at intravenous doses of 0.04 microg/kg 3 times daily increased bile flow and improved serum bilirubin levels. However, patients with advanced liver disease did not respond to sincalide therapy. Long-term follow-up data on sincalide effects on liver disease progression are not yet available. CONCLUSIONS: Sincalide improved the signs of cholestasis. However, its long-term effects in preventing and treating PN-associated gallbladder disease remain unknown and its routine use for this indication cannot be recommended at this time.     

Rimonabant--a selective CB1 antagonist

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety of rimonabant, a new selective cannabinoid receptor antagonist. DATA SOURCES: Primary literature and review articles were obtained via a MEDLINE search (1966-November 2004) using the key terms obesity, smoking cessation, cannabinoid, rimonabant, SR 141716, and SR 141716a. Additional studies and abstracts were identified from the bibliographies of reviewed literature. STUDY SELECTION AND DATA EXTRACTION: Studies and review articles related to rimonabant and the endocannabinoid system were reviewed. Data pertinent to this article were included. DATA SYNTHESIS: Rimonabant is a selective cannabinoid receptor antagonist. Recent data have demonstrated beneficial effects of rimonabant in obesity, smoking cessation, and metabolic syndrome. Animal studies using rimonabant have shown a positive role for reducing hunger, caloric intake, and body weight and in increasing satiety. In humans, rimonabant appears to be effective for treatment of obesity and smoking cessation. Ongoing studies will examine the effect of rimonabant on obesity, metabolic syndrome, smoking cessation, and alcohol abuse. To date, the incidence of adverse effects with rimonabant has been slightly greater than placebo, with the most common being nausea. CONCLUSIONS: Rimonabant appears to be a promising drug in an entirely new class called selective cannabinoid CB1 receptor antagonists. The drug may be approved for treatment of obesity and smoking cessation in 2005. Additional studies are ongoing that may provide information on other clinical uses for this medication.