By Louis Kuritzky, MD
Orlistat in Overweight Patients with Type 2 Diabetes
Recently, it has been acknowledged that metformin (MET), in contrast to insulin secretagogues or insulin supplementation, is weight neutral or even associated with weight loss. Unfortunately, most DM2 patients are, or will be, on more than one medication, which may complicate weight management.
Of the 2 medications currently available for long-term management of obesity, both sibutramine and orlistat (ORL) have been shown to provide statistically significant weight reduction in DM2. Whether such effects might extend to persons specifically receiving DM2 treatment with metformin has not been previously studied. In particular, since both MET and ORL are associated with GI symptoms, the tolerability as well as efficacy of this combination merits clarification.
In this study, ORL (n = 249) or placebo (n = 254) was administered t.i.d to patients on stable doses of MET. Some patients were also receiving sulfonylureas (SFU) in addition to MET. Insulin, thiazolidinedione, or alpha-glucosidase treatments were exclusionary from the study. Patients were treated for 1 year.
ORL was associated with clinically important, as well as statistically significant improvements in A1c (mean = 0.9 decrease); LDL, triglycerides, and blood pressure were all favorably affected in comparison to placebo. Mean weight loss was 4.7 kg on ORL (vs 1.8 kg, placebo). Although GI complaints were more frequent in the ORL group, withdrawal due to adverse events was actually more frequent in the placebo group. In overweight diabetics on MET, ORL is well tolerated and effective for multiple factors pertinent to diabetic control.
Miles JM, et al. Diabetes Care. 2002; 25:1123-1128.
Sleep Attacks in Patients Taking Dopamine Agonists
The term "sleep attack" is defined as ". . . an event of overwhelming sleepiness that occurs without warning or with a prodrome sufficiently short or overpowering to prevent protective measures." It has already been recognized that dopaminergic drugs, such as those commonly used in Parkinsonism (eg, levodopa, ropinirole, bromocriptine), are associated with somnolence and motor vehicle accidents (MVA). Identification of the frequency of sleep attacks is relevant to risk reduction.
Homann and colleagues identified 20 publications that included suspect events (n = 124), further dividing them into definite, probable, and possible sleep attacks. Ten of 17 events occurring during driving lead to MVA; however, numerous attacks happened even during ambulatory activities, such as walking or standing.
In this review, as many as 30% of patients receiving dopamine agonists for Parkinson’s disease (PD) had sleep attacks, regarded by Homann et al as a class phenomenon, rather than due to a specific agent. Additionally, dose reduction was not reliably associated with remission of sleep attacks, and of course could risk lesser symptom control of PD. It has been recommended that persons taking pramipexole and ropinirole not drive. Short of not driving, it is uncertain which measures should be exercised for Parkinson’s patients taking other dopaminergic medications. Indeed, there remains some controversy about the existence of sleep attacks distinct from simple somnolence. The descriptions in this communication argue for the definition of sleep attacks as a separate entity.
Homann CN, et al. BMJ. 2002;324: 1483-1487.
Probiotics in Prevention of AAD
The consequences of antibiotic-associated diarrhea (AAD) are potentially far ranging. Though thoughtful antibiotic selection and application can reduce the frequency of AAD, numerous clinical situations will require antibiotics for which the likelihood of AAD is known to be significant. Probiotics (PRO) are microorganisms with therapeutic potential—some nonpathogenic organisms appear to inhibit the growth of pathogens. Saccharomyces boulardii, a nonpathogenic yeast, has been reported to destroy the receptor site for C difficile toxin A and B through a protease enzyme.
In this report, 9 double-blind, placebo-controlled trials were analyzed. Agents used included S boulardii, lactobacilli, and enterococcus. In each of the trials, the PRO was administered concomitantly with the antibiotics. Antibiotics studied included amoxicillin, clindamycin, and multi-drug regimens.
Concomitant PRO administration was associated with an approximately 60% reduction in odds ratio for AAD. PRO are well tolerated, without known serious adverse effects, and though they transiently colonize the gut, upon cessation of therapy they are generally rapidly cleared from the GI microbial population. This meta-analysis indicates PRO may offer valuable reductions in the frequency of AAD, and further study is suggested.
D’Souza AL, et al. BMJ. 2002;324: 1361-1364.
Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.
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