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糖尿病研究与治疗的最新进展

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1. Efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes mellitus: a meta-analysis.

Arch Intern Med. 2004 Jul 12;164(13):1395-404.

Norris SL, Zhang X, Avenell A, Gregg E, Schmid CH, Kim C, Lau J. Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA. scn5@cdc.gov

BACKGROUND: Obesity is closely related to type 2 diabetes mellitus, and weight reduction is an important part of the care delivered to obese persons with diabetes. The objective of this review was to assess the efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes.

METHODS: A systematic review of the literature was performed, and studies were included if pharmacotherapy was used as the primary strategy for weight loss among adults with type 2 diabetes. Published and unpublished studies with any design were included. A random effects model was used to combine outcomes from randomized controlled trials.

RESULTS: Sufficient data for the meta-analysis were available for fluoxetine, orlistat, and sibutramine. Fourteen randomized, placebo-controlled trials were included in the review, with a total of 2231 patients. Pharmacotherapy produced modest reductions in weight for fluoxetine (3.4 kg [95% confidence interval (CI), 1.7-5.2 kg] at 8-16 weeks of follow-up; 5.1 kg [95% CI, 3.3-6.9 kg] at 24-30 weeks; and 5.8 kg [ 95% CI, 0.8-10.8 kg] at 52 weeks); orlistat (2.6 kg [95% CI, 2.1-3.2 kg] [2.6% loss] at 52 weeks); and sibutramine (4.5 kg [95% CI, 1.8-7.2 kg] [3.3% loss] at up to 26 weeks). Glycated hemoglobin was also modestly reduced: fluoxetine (1.0% [95% CI, 0.4%-1.5%] at 8-16 weeks; 1.0% [95% 0.6%-1.4%] at 24-30 weeks; and 1.8% [95% CI, -0.2%-3.8%] at 52 weeks); orlistat (0.4% [95% CI, 0.3%-0.5%]); and sibutramine (0.7% [95% CI, -0.5%-1.9%]). Gastrointestinal adverse effects were common with orlistat; tremor, somnolence, and sweating with fluoxetine; and palpitations with sibutramine.

CONCLUSIONS: Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 26 to 52 weeks. However, the magnitude of weight loss was modest, and the long-term health benefits and safety remain unclear. Interventions that combine pharmacologic therapy with intensive behavioral interventions may be more effective but need additional research.

2. Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials.

Int J Obes Relat Metab Disord. 2003 Dec;27(12):1437-46.

Padwal R, Li SK, Lau DC. Division of Internal Medicine, University of Alberta Hospital, 2E3. Walter C Mackenzie Health Sciences Centre, Edmonton, AB, Canada. rpadwal@yahoo.com

CONTEXT: Safe and effective strategies to curb rising obesity prevalence rates are urgently needed and medications may play a more prominent role in future therapeutic regimens.

OBJECTIVE: To review systematically the long-term efficacy and safety of approved antiobesity medications.

DATA SOURCES: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Current Science Meta-register of Controlled Trials, and reference lists of original studies and reviews were searched. Drug manufacturers and two obesity experts were contacted. No language restrictions were imposed.

STUDY SELECTION: Double-blind, randomized controlled studies of approved antiobesity medications with follow-up periods of 1 y or greater were eligible for inclusion.

DATA EXTRACTION: Two reviewers independently assessed all potentially relevant studies for inclusion and methodological quality using standardized abstraction forms.

RESULTS: A total of 11orlistat (n=6021) and three sibutramine (n=929) studies met inclusion criteria. Attrition rates averaged 33% in orlistat studies and 48% in sibutramine studies. A random effects model was used for meta-analysis. Compared to placebo, orlistat-treated patients displayed a 2.7 kg (95% CI: 2.3-3.1 kg) or 2.9% (95% CI: 2.3-3.4%) greater reduction in weight and patients on sibutramine displayed a 4.3 kg (95% CI: 3.6-4.9 kg) or 4.6% (95% CI: 3.8-5.4%) greater weight reduction after 1 y of follow-up. The number of patients achieving 10% or greater weight loss was 12% (95% CI: 8-16%) higher with orlistat and 15% (95% CI: 4-27%) higher with sibutramine compared to placebo. Orlistat caused gastrointestinal side effects and sibutramine increased blood pressure and pulse rate.

CONCLUSION: There is a relative paucity of long-term studies of antiobesity agents. In weight loss trials of 1-y duration, orlistat and sibutramine appear modestly effective in promoting weight loss. Longer, more methodologically rigorous studies that are powered to examine end points such as mortality and cardiovascular morbidity are required.

3. A systematic review of the clinical effectiveness of orlistat used for the management of obesity.

Obes Rev. 2004 Feb;5(1):51-68.

O'Meara S, Riemsma R, Shirran L, Mather L, ter Riet G. Department of Health Sciences, NHS Centre for Reviews and Dissemination, University of York, York, UK. smo4@york.ac.uk

The aim of this paper is to assess the clinical effectiveness of orlistat used for the management of obesity. Nineteen electronic databases were searched for randomized controlled trials evaluating the effectiveness of orlistat for weight loss or maintenance of weight loss in overweight or obese patients.

Each included trial was assessed for methodological quality. Statistical pooling was performed when trials were considered to be sufficiently similar. Twenty-three trials were eligible for inclusion.

Placebo-controlled trials recruiting patients with uncomplicated obesity reported statistically significant differences in favour of orlistat for weight loss and changes in obesity-related risk factors at all time points. Trials in obese patients with defined risk factors at baseline showed similar results, however, smaller effect sizes were observed in patients with type 2 diabetes.

The effectiveness of orlistat relative to other anti-obesity drugs is currently unclear. When orlistat was added to simvastatin, this proved to be more effective for weight loss than either drug used individually. Orlistat use is associated with a higher incidence of gastrointestinal adverse events compared with placebo.

In conclusion, orlistat is more effective than placebo in promoting weight loss, maintenance of weight loss, and improving cardiovascular risk factor profiles. Baseline parameters of patients seen in clinical practice should be taken into account when considering treatment.

4. The efficacy and safety of sibutramine for weight loss: a systematic review.

Arch Intern Med. 2004 May 10;164(9):994-1003.

Arterburn DE, Crane PK, Veenstra DL. Department of Veterans Affairs, Puget Sound Health Care System, Seattle, WA, USA. david.arterburn@uc.edu

BACKGROUND: The primary goal of weight loss is to prevent or reduce obesity-associated morbidity and mortality by improving cardiovascular and metabolic risk factors. We conducted a systematic review to assess the efficacy and safety of sibutramine hydrochloride for weight loss.

METHODS: In April 2002, we searched MEDLINE, EMBASE, the Cochrane Library, and 7 other computerized bibliographic search tools using the keywords "sibutramine," "Meridia," and "Reductil" (in all languages and all available years). The authors and the manufacturer were contacted. We reviewed randomized placebo-controlled trials of sibutramine, 10 to 20 mg/d, in obese adults. Methodological quality was assessed.

RESULTS: A total of 29 trials had sufficient data for analysis after including unpublished data from 10 authors. The summary mean differences in weight loss, sibutramine minus placebo, for the 3-month and 1-year trials were -2.78 kg (95% confidence interval, -2.26 to -3.29 kg) and -4.45 kg (95% confidence interval, -3.62 to -5.29 kg), respectively. The 6-month trials were statistically heterogeneous, and evidence of publication bias was found. One trial found that sibutramine maintains weight loss better than placebo at 2 years. Weight loss with sibutramine was associated with modest increases in heart rate and blood pressure, small improvements in high-density lipoprotein cholesterol and triglycerides levels, and, among diabetic patients, small improvements in glycemic control. There was no direct evidence that sibutramine reduces obesity-associated morbidity or mortality.