Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.

Safety and Efficacy of Newest Pharmocotherapy for Diabetes: The Incretins

Despite an increasing array of methods for control of diabetes, not even half of patients currently have attained and maintain an A1c less than 7%. Hence, new tools which may enhance achievement of goals are welcome, but only if the efficacy, safety, and tolerability is also acceptable. Because the incretins (ie, exenatide, sitagliptin) are typically weight-neutral, or even associated with weight loss, they are attractive to diabetic patients, many of whom struggle with weight management issues. This class of agents is complementary with many of the commonly used pharmacotherapies for diabetes. Currently, only one oral incretin (sitagliptin, trade name Januvia), and one parenteral incretin (exenatide, trade name Byetta) are available in the United States. Promising new delivery systems for exenatide, allowing once-weekly administration, and development of additional oral incretins (eg, vildagliptin) may provide even further diversity for this class of agents.

In this systematic review and meta-analysis, encompassing 29 clinical trials and over 20,000 study subjects, incretins were found to be comparably effective to other oral agents for lowering of glucose, with modest adverse effect profiles. Because there is a paucity of trials lasting more than 30 weeks, true long-term safety remains to be determined. There are no large clinical trials of subjects treated with incretins to inform us of clinical endpoints such as diabetes-related death or cardiovascular disease. These data are reassuring that incretin therapy is safe and effective.

Amori RE, et al. JAMA. 2007;298(2):194-206.


Optimum Duration of Treatment for Hepatitis C

Currently, we may be able to cure a substantial majority of persons with hepatitis C. Until very long- term data are available, the current gold standard for cure is sustained viral response (SVR), defined as an absence of detectible virus 6 months after cessation of treatment. The good news is that for persons with HCV genotype 2 or 3, a "traditional" regimen of 24 weeks treatment with peginterferon plus ribavirin produces a SVR in 80% of cases. Current treatment regimens are expensive and have adverse effects, so shortening the course without compromising efficacy would be valuable.

Earlier data has shown that for HCV treatment subgroups that promptly clear HCV RNA (within 4 weeks), SVR is attained with as few as 12-16 weeks of treatment. To prospectively confirm that shorter treatment courses are as efficacious as longer ones, Shiffman, et al compared a 16-week course of therapy with a 24-week course in 1,469 study subjects.

The efficacy of the shorter course of therapy to achieve a SVR was significantly less than the longer course (62% vs 70%, p <0.001). The "traditional" 24-week therapeutic course should remain standard for all but exceptional cases.

Shifffman ML, et al. N Engl J Med 2007;357:124-134.


Estrogen and Coronary Calcification

Analysis of data from the Women's Health Initiative (WHI) suggests that for younger women (age 50-59), the relationship between estrogen replacement and coronary health may not be the same as for the more mature women in this trial. Even though the overall "take-away" from the WHI is that women should not receive hormone replacement with hopes of reducing cardiovascular risk, reconsideration of subgroups suggests that older women (mean age of WHI participants = 63) respond differently than younger women.

The use of electron beam computed tomography (EBCT) to detect coronary calcium has been consistently supported as an accurate indicator of the presence of coronary calcification, and equally valid to exclude the same. Manson, et al performed an analysis of younger women (age 50-59) from the WHI who underwent EBCT (or multidetector-row CT) at baseline and after 8.7 years. The treatment arm of the WHI actually lasted only 7.4 years, so the followup CT was obtained 1.3 years after the trial had concluded.

Coronary calcium scores were sub-stantially lower amongst women who had received estrogen than placebo; for those with the highest level of adherence to estrogen, the calcium scores were even lower. These data indicate that for younger women (age 50-59), estrogen replacement therapy is associated with lower frequency and level of coronary artery calcification, a respected surrogate for risk of myocardial infarction.

Manson JE, et al. N Engl J Med. 2007;356:2591-2602.