Alpha-glucosidase Inhibitors May Reduce the Risk of Type 2 Diabetes

Clinical Question

Does acarbose (Precose) decrease the incidence of diabetes when used to treat impaired glucose tolerance or impaired fasting glucose?

Evidence-Based Answer

The literature shows that acarbose can reduce the risk of type 2 diabetes in patients with impaired glucose tolerance or impaired fasting glucose. However, it is unclear whether the drug stops or delays the development of the disease or masks the diagnosis. There is no evidence that acarbose use reduces overall mortality or cardiovascular morbidity. The high incidence of adverse effects may also limit the use of acarbose for the prevention of diabetes.

Practice Pointers

Alpha-glucosidase inhibitors work at the brush border of the small intestine, delaying carbohydrate absorption and subsequently lowering postprandial peaks in glucose levels. Two alpha-glucosidase inhibitors, acarbose and miglitol (Glyset), are approved for use in the United States. Guidelines do not recommend alpha-glucosidase inhibitors as monotherapy for diabetes; however, whether this drug class can prevent overt diabetes in persons with prediabetes has been questioned.

In this Cochrane review, the authors assessed the effects of alpha-glucosidase inhibitor use in persons with impaired glucose tolerance or impaired fasting glucose. The primary outcomes included the incidence of type 2 diabetes, morbidity related to impaired glucose metabolism, and total mortality. Secondary outcomes included glycemic control, blood pressure and lipid effects, fasting and post-carbohydrate load insulin levels, and the incidence of adverse effects. Five studies with 2,360 total patients were included in this review. One study followed patients for one year, two for three years, one for five years, and one for six years. Most of the studies used acarbose, 50 mg orally, three times per day.

The highest-quality study demonstrated that acarbose decreases the incidence of type 2 diabetes; 10 persons need to be treated for three years to prevent one person from developing diabetes. The study also demonstrated that acarbose decreases the incidence of cardiovascular events; 50 patients need to be treated to prevent one cardiovascular event. However, the study results are based on a small number of events and could not be confirmed by other studies.

Two smaller studies also demonstrated that acarbose decreases the risk of type 2 diabetes; however, there are two important concerns about this finding. One of the studies showed that after acarbose was discontinued, more patients who took acarbose became diabetic than patients who took placebo (15.4 versus 10.6 percent). This raises the question of whether acarbose was preventing or merely masking the diagnosis of diabetes. The second concern is adverse effects: 31 percent of participants discontinued acarbose, compared with 19 percent of participants in the placebo arm; one in four participants had gastrointestinal adverse effects. No significant differences between the two groups were found in total mortality, lipid levels, or blood pressure measurements. Patients taking acarbose had a nonsignificant decrease in body weight of 2 lb, 10 oz (1.2 kg). Acarbose had no effect on glycemic control, lipid measurements, or blood pressure.

The incidence of diabetes increased by 54 percent in the United States from 1997 to 2004.1 Diet and exercise remain the mainstays of diabetes prevention. A systematic review showed that diet and exercise reduced the incidence of diabetes by 50 percent over one year without adverse effects.2 One study in the Cochrane review showed that, compared with diet and exercise, five patients need to be treated with acarbose to prevent one patient from developing diabetes in five years. Acarbose, like metformin (Glucophage), is promising but cannot be definitely recommended. The benefits of acarbose must be weighed against the high incidence of adverse effects.

Antiretroviral Prophylaxis for Occupational Exposure to HIV

Clinical Question

Should health care workers with occupational exposure to human immunodeficiency virus (HIV) receive postexposure antiretroviral prophylaxis?

Evidence-Based Answer

There are no controlled trials of postexposure prophylaxis for persons with occupational exposure to body fluids potentially infected with HIV. Based on one case-control study, individually selected antiretroviral therapy, initiated soon after exposure, is recommended. Treatment should continue for four weeks or until the source body fluid tests HIV negative.

Practice Pointers

The Centers for Disease Control and Prevention (CDC) defines occupational HIV exposure as a percutaneous injury (e.g., a needlestick, cut from a sharp object) or contact of mucous membranes or nonintact skin (e.g., skin that is chapped, abraded, or affected by dermatitis) with blood, tissue, or other body fluids that are potentially infected with HIV.1 Potentially infectious fluids include cerebrospinal, synovial, pleural, peritoneal, pericardial, and amniotic fluids. Feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomit are not considered infectious unless visibly bloody. The risk of HIV transmission is approximately 0.3 percent after percutaneous exposure to infected blood and 0.09 percent after mucous membrane exposure. The risk of transmission varies with the type of exposure and infected fluid.1

The authors of this Cochrane review searched the literature from 1985 to May 2005. They found no controlled trials of postexposure prophylaxis, but found one case-control study. Participants were health care workers with occupational, percutaneous exposure to HIV-infected blood. Patients in the case group had HIV seroconversion temporally associated with the exposure and no other reported concurrent exposure to HIV. Participants in the control group remained seronegative six months after exposure.

An increased risk of HIV transmission was associated with deep injury, visible blood on the device, procedures involving a needle placed in the source patient's blood vessel, and terminal illness in the source patient. Zidovudine (Retrovir) use after exposure was associated with a lower risk of HIV transmission. Most patients took at least 1,000 mg of zidovudine per day starting within four hours of exposure.

Of 58 health care workers who received postexposure prophylaxis, 71 percent had adverse effects, including nausea (24 percent), fatigue (22 percent), emotional distress (13 percent), and headache (9 percent). Although patients who received a three-drug regimen reported more adverse effects, the drop-out rate in these patients was similar to that in patients who received fewer drugs.

The CDC recommends postexposure prophylaxis for health care workers who have occupational exposure to blood infected with HIV, and it recommends considering prophylaxis for health care workers with percutaneous injuries from sources with unknown HIV status who have risk factors or who are from settings where HIV exposure is likely.1 Prophylaxis should be initiated as soon as possible, ideally within hours, not days, of exposure. Therapy should continue for four weeks or until the source blood tests HIV negative. Selection of prophylactic medication should be determined in consultation with an expert in antiretroviral therapy and HIV transmission.1 If expert consultation is not immediately possible, more information on prophylactic regimens is available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5409a1.htm and http://www.ucsf.edu/hivcntr/Hotlines/PEPline.html.