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.

Can Exenatide be Substituted for Insulin?

Historically, insulin (INS) is the only agent that can consistently attain glycemic goals once patients have failed oral antidiabetic agents (OADA). Even when patients readily accept INS treatment, weight gain and hypoglycemia sometimes remain daunting obstacles. Hence, another highly-efficacious agent is very desirable.

Exenatide (EXNT) is a member of the class of OADA known as incretins. While providing a substantial glucose-lowering effect, EXNT is not associated with weight gain; indeed, weight reduction is commonly seen in patients treated with EXNT. Previous non-inferiority trials have shown comparable glucose control in patients failing OADA to whom either insulin or EXNT are added.

Davis, et al studied type 2 diabetes patients who were already on a combination of INS + OADA. Half of the study subjects (n=45) were switched to EXNT instead of INS, and the other half continued on INS. No changes were made in oral agents, diet, or exercise, although if hypoglycemia occurred, sulfonylurea dose was cut in half.

At the 16-weeks endpoint of the study, the change in A1C between the groups was not statistically significant. Although the incidence of hypoglycemia was similar in the EXNT and INS treatment groups, weight loss was significantly more common in the EXNT group. This small study is encouraging for patients who find insulin utilization problematic. EXNT might provide equally favorable control.

Davis SN, et al. Diabetes Care. 2007;30(11):2767-2772.

Treatment of Osteoporosis Saves Bones AND Lives

Hip fracture (HPFx) portends risk: mortality rates as high 25% in the year following HPFx have been reported. Once a HPFx has occurred, the risk of new fracture is 2.5 times greater than in persons without such history. Zoledronic acid (ZOL), a parenteral bisphosphonate (like oral alendronate, risedronate, ibandronate, but parenterally administered) is an intervention which could potentially change the balance of these negative outcomes.

The HORIZON trial (Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Recurrent Fracture Trial) randomized 2,137 patients who had sustained a HPFx to either a once-yearly ZOL injection or placebo. All subjects (both groups) received supplementation with vitamin D and calcium.

At 1.9 years of follow-up, the ZOL recipients enjoyed not only a 35% relative risk reduction in new fractures, but also a 28% relative risk reduction in mortality.

Some earlier data has reported a meaningful incidence of atrial fibrillation in persons receiving ZOL, as well as (rarely) osteonecrosis. Neither was seen in this trial, nor was the rate of stroke increased (as would be anticipated were ZOL to induce occult atrial fibrillation). No serious adverse events were attributed to ZOL, though transient systemic malaise-like symptoms were seen. ZOL holds promise in persons with very-high risk osteoporosis, such as those who have already sustained a HPFx.

Lyles KW, et al. N Engl J Med. 2007;357:1799-1809.

MRSA in These United States

MRSA (methicillin-resistant staphylococcus aureus) has attained sufficient notoriety that it is not uncommon these days for patients to walk in, display their ill part, and ask "Do you think it's MRSA?" As recently as 10 years ago, MRSA might often be considered an infectious etiologic afterthought, and certainly only in persons who had been hospitalized. Today, it represents the most common etiology of cellulitis and cutaneous abscess presenting to Emergency Rooms.

To gain a better perspective on the population burden of MRSA, 9 US communities participated in surveillance for MRSA from July, 2004 to December 2005. Although admittedly sometimes a "hazy line," MRSA infections were subclassified as either health care associated (MRSA-h) or community associated (MRSA-c).

Over the 18-month surveillance period, almost 9,000 MRSA cases were identified, the slight majority of which (58.4%) were MRSA-h. The incidence was substantially greater in blacks (over 2 fold) and women (1.4 fold). The mortality of invasive MRSA was 17.8%. If these data are extrapolated to the entire USA, it would be estimated that 94,360 MRSA infections occur, including 18,650 deaths. MRSA is a burgeoning public health issue. Clinicians are encouraged to continue to make a presumptive diagnosis of MRSA in appropriate clinical settings and promptly institute currently recommended treatment.

Klevens RM, et al. JAMA. 2007;298(15):1763-1771.