Protease inhibitors may cause diabetes, FDA warns

Close monitoring of glucose levels urged

A new class of drugs recently recommended for use as chemoprophylaxis for health care workers following some occupational blood exposures might contribute to increases in glucose levels and even diabetes, according to a health advisory issued by the U.S. Food and Drug Administration (FDA).

The FDA has received 83 reported cases of new or exacerbated diabetes mellitus and hyperglycemia in HIV-infected patients taking protease inhibitors, a new class of drugs licensed for HIV treatment. Last year, the Public Health Service issued guidelines recommending combination prophylactic therapy that includes protease inhibitors for the highest-risk occupational exposures,1 prompting concerns about the drug’s toxicity in healthy people. (See Hospital Employee Health, August 1996, pp. 85-92.)

Information on the diabetes-related side effects was obtained from the drug manufacturers, and no information presently is available about whether any of the 83 cases involve people taking protease inhibitors as prophylaxis, says FDA spokeswoman Ivy Kupec.

The four approved protease inhibitors — indinavir (Crixivan, from Merck Research Laboratories); saquinavir (Invirase, from Hoffman-LaRoche); ritonavir (Norvir, from Abbott Laboratories); and nelfinavir (Viracept, from Agouron Pharmaceuticals) — soon will carry revised labeling warning of the potential side effect.

The FDA notes that while many patients who discontinued protease inhibitor therapy saw a reduction in their symptoms, no definitive causal link between the drugs and diabetes or hyperglycemia has been established. Some patients had other medical conditions that required therapy with agents associated with development of diabetes or hyperglycemia.

In the 83 reported cases, symptoms such as increased thirst and hunger, increased urination, unexplained weight loss, fatigue, and dry, itchy skin occurred an average of approximately 76 days from starting protease inhibitor therapy. But the FDA is aware of cases where symptoms appeared as soon as four days after starting therapy.

FDA: Benefits outweigh risks

Of the 83 patients, 27 required hospitalization, including six life-threatening cases. Five cases resulted in ketoacidosis. About 150,000 Americans are taking protease inhibitors, and the FDA notes that the incidence of diabetes is infrequent; therefore, discontinuing therapy is not recommended. Many patients who developed diabetes were able to control it with insulin or other agents, and the FDA says it believes the drug’s benefits outweigh its risks.

The agency recommends closely monitoring glucose levels and urges health care professionals to report cases of diabetes and hyperglycemia, or other serious toxicity associated with the use of protease inhibitors, to one of the following:

• FDA Medwatch program, (800) FDA-1088, fax (800) FDA-0178;

• Merck Research Laboratories, (800) 672-6372;

• Hoffman-LaRoche, (800) 526-6367;

• Abbott Laboratories, (800) 633-9110;

• Agouron Pharmaceuticals, (888) 847-2237.


1. Centers for Disease Control and Prevention. Update: Provisional Public Health Service recommendations for chemoprophylaxis after occupational exposure to HIV. MMWR 1996; 45:468-472.