Pharmacotherapy for weight loss in adults with type 2 diabetes mellitus.

BACKGROUND: Obesity is closely related to type 2 diabetes and long-term weight reduction is an important part of the care delivered to obese persons with diabetes. OBJECTIVES: To assess the efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes. SEARCH STRATEGY: Computerized searches were performed of MEDLINE (January 1966 to May 2004), EMBASE (January 1974 to May 2004, Web of Science (January 1981 to May 2004, and other electronic bibliographic databases, supplemented with hand searches of reference lists and selected journals. SELECTION CRITERIA: Randomized, controlled trials were included where pharmacotherapy was used as the primary strategy for weight loss among adults with type 2 diabetes. Published and unpublished literature in any language and with any study design was included. DATA COLLECTION AND ANALYSIS: Two reviewers abstracted data and the quality of included studies was evaluated by assessing potential attrition, as well as selection and measurement bias, and a Jadad score was obtained. Effects were combined using a random effects model. MAIN RESULTS: A sufficient number of studies were available for a quantitative synthesis for fluoxetine, orlistat, and sibutramine. Twenty two randomized controlled trials were included in the review, with a total of 296 participants for fluoxitine, 2036 for orlistat, and 1047 for sibutramine. Pharmacotherapy produced modest reductions in weight for fluoxetine (5.1 kg (95% confidence interval [CI], 3.3 - 6.9) at 24 to 26 weeks follow up; orlistat 2.0 kg (CI, 1.3 - 2.8) at 12 to 57 weeks follow-up, and sibutramine 5.1 kg (CI, 3.2 - 7.0) at 12 to 52 weeks follow-up. Glycated hemoglobin also modestly and significantly reduced for fluoxetine and orlistat. Gastrointestinal side effects were common with orlistat; tremor, somnolence and sweating with fluoxetine; and palpitations with sibutramine. Some studies, using a variety of study designs, were available on other drugs and a significant decrease in weight was noted in three studies of mazindol, one of phenmetrazine, two of phentermine. No studies were identified that fit inclusion criteria for pseudophedrine, ephedra, sertraline, yohimbine, amphetamine or its derivatives, bupropion, topiramate, benzocaine, threachlorocitric acid, sertraline, and bromocriptine. AUTHORS' CONCLUSIONS: Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 12 to 57 weeks. The magnitude of weight loss is modest, however, and the long-term health benefits remain unclear. The safety of sibutramine is uncertain. There is a paucity of data on other drugs for weight loss or control in persons with type 2 diabetes.

Safety of nifedipine in angina pectoris: a meta-analysis.

-Our objective was to compare cardiovascular event rates in patients with stable angina receiving nifedipine as monotherapy or combination therapy and in active drug controls. A MEDLARS search of published articles from 1966 to 1995 in English, French, German, Italian, or Spanish, supplemented by a manual search of bibliographies, identified 60 randomized controlled trials that met protocol criteria. Blinded articles were extracted by 2 physicians. The pooled risks of death, withdrawal, and cardiovascular event were computed and expressed as odds ratios (ORs) for all nifedipine formulations and relative to same study control drug regimens. Thirty cardiovascular events were reported in 2635 nifedipine exposures (1.14%) and 19 events in 2655 other active drug exposures (0.72%). Unadjusted ORs for nifedipine versus controls were 1.40 (95% CI, 0.56 to 3.49) for major events (death, nonfatal myocardial infarction, stroke, revascularization procedure), 1.75 (95% CI, 0.83 to 3.67) for increased angina, and 1.61 (95% CI, 0.91 to 2.87) for all events (major events plus increased angina). Episodes of increased angina were more frequent on immediate-release nifedipine (OR, 4.19 [95% CI, 1.41 to 12.49]) and on nifedipine monotherapy (OR, 2.61 [95% CI, 1.30 to 5.26]). The OR for immediate-release nifedipine was significantly higher than that for sustained-release/extended-release nifedipine (P=0.001), and the OR for nifedipine monotherapy was higher than that for nifedipine combination therapy (P=0.03). Increased risks of cardiovascular events in patients with stable angina on nifedipine were due primarily to more episodes of increased angina, confined to the immediate-release formulation and to nifedipine monotherapy.

Safety of nifedipine in patients with hypertension: a meta-analysis.

Our objective was to compare cardiovascular event rates in patients with mild or moderate hypertension who received nifedipine with active drug controls. We performed a MEDLARS search using the MeSH heading "hypertension" and the text word "nifedipine" to identify all articles that were published between 1966 and August 1995 in English, French, German, Italian, and Spanish languages and that involved human subjects. The computerized search was supplemented by a manual search of article bibliographies. Review of 1880 citations revealed 98 randomized controlled clinical trials that met protocol criteria. Articles were extracted independently by two doctors who were blinded for author, institution, and treatment regimen, using a structured, pretested extraction form. Differences of opinion were resolved by consensus. Fourteen events occurred in 5198 exposures (0.27%) to nifedipine and 24 events in 5402 exposures (0.44%) to other active drug controls. Unadjusted odds ratios for nifedipine versus controls were 0.49 (95% confidence interval [CI], 0.22-1.09) for definitive events (death, nonfatal myocardial infarction or stroke, revascularization procedure) and 0.61 (95% CI, 0.31-1.17) for all events (definitive plus increased angina). The odds ratio for nifedipine monotherapy (sustained- or extended-release in 91% of exposures) was nonsignificantly higher for definitive and all events (odds ratio, 1.40; 95% CI, 0.49-4.03 and odds ratio, 1.39; 95% CI, 0.59-3.32, respectively). The odds ratio for nifedipine in combination with another drug was significantly lower for definitive and all events (odds ratio, 0.09; 95% CI, 0.01-0.66 and odds ratio, 0.15; 95% CI, 0.03-0.65, respectively). Differences in odds ratio for nifedipine monotherapy and combined therapy were statistically significant (P=.02 for definitive events and P=.001 for all events). Results support the safety of sustained- and extended-release nifedipine in the treatment of mild or moderate hypertension when it is used in combination with other drugs.

Searching for signals: mortality and cardiovascular events in published randomized control trials of nifedipine in ischemic heart disease and hypertension.

UNLABELLED: META-ANALYSIS: A meta-analysis of published randomized control trials of nifedipine in hypertension and stable angina pectoris was performed. RESULTS: The results suggest a formulation-dependent increased risk of mortality and adverse cardiovascular outcomes for monotherapy use in patients with stable angina pectoris. No increased risk was seen in the hypertension studies.

Safety, accuracy, and diagnostic yield of needle localization biopsy of the breast performed using local anesthesia.

BACKGROUND: In changing our technique to performing needle localization breast biopsies (NLBB) using local anesthesia in an outpatient setting, we investigated whether or not our complication rates with local anesthesia were acceptable when compared with complications from a cohort of biopsies of the breast performed for palpable masses. We were also interested in determining whether or not our rate of missed biopsies was within acceptable ranges. STUDY DESIGN: Complications occurring in 283 patients who underwent 301 NLBB using local anesthesia between 1983 and 1991 were compared with complications occurring after excision of 249 palpable masses of the breast excised using local anesthesia during this period. RESULTS: Complications associated with NLBB were missed lesions, six (1.99 percent) of 301; hematoma, 12 (3.99 percent) of 301; abscess, three (0.99 percent) of 301; seroma, one (0.33 percent) of 301, and wound separation, two (0.66 percent) of 301, for a total of 24 complications (7.96 percent). These rates were not statistically different from the rates of complication after biopsies of palpable lesions using local anesthesia (p < 0.49). The 301 NLBB revealed 87 carcinomas (28.9 percent); 50 invasive and 37 in situ. Of the nonpalpable carcinomas, 43 percent were in situ. Only 11 percent carcinomas, 43 percent were in situ. Only 11 percent of the palpable lesions were in situ (p < 0.001). Forty-four patients with nonpalpable invasive carcinoma had a 25 percent rate of positive axillary lymph nodes. CONCLUSIONS: Needle localization breast biopsies can be performed using local anesthesia exclusively with less than a 2 percent chance of missed lesions and complication rates similar to those associated with biopsies of palpable lesions. The biology of these lesions varies. Although there is a high rate of in situ carcinoma, there is a significant rate of node positivity in the patients with nonpalpable invasive carcinoma.