Diabetes: Am I On the Most Effective Medication? Rahim Ali, PharmD. Candidate, University of Florida College of Pharmacy We all know or have heard something about diabetes. For example, many may have heard in the news about Avandia, a drug used in the treatment of diabetes which has been linked to an increased risk for heart attack. Many may also have heard of the drug metformin, a very effective and relatively safe drug, but is contraindicated in patients with poor kidney function. Others may have friends that take daily injections of insulin to control their blood sugar or have witnessed someone have a bout hypoglycemia, or low blood sugar. Diabetes has become epidemic in the past few decades. As the number of medications available to treat it continues to increase, pharmacists are educating patients and physicians alike of the most effective medications available, their potential side effects, contraindications, and synergistic combinations. This knowledge is especially valuable in the treatment of diabetes in the elderly, since optimizing therapy in this population can reduce pill burden and limit side effects. This article serves to give information about the pathophysiology of diabetes and highlight the most effective initiation of treatment for this disease as outlined by the recent Consensus Algorithm published by the American Diabetes Association. Diabetes is a disorder characterized by hyperglycemia, or high levels of glucose in the blood. Symptoms of hyperglycemia can be frequent urination, excessive thirst, and extreme hunger. Whether someone has these symptoms or other symptoms, such as weight loss and increased fatigue, diabetes can be diagnosed by checking the blood sugar with a glucose meter. The normal range is between 70 – 110 mg/dL; a number greater than or equal to 200 mg/dL after repeat testing usually means diabetes. Glucose, the primary source of energy in the body, is only beneficial if it is able to move out of the bloodstream and into the tissues where it is needed. Insulin is the signal to the tissues that there is glucose available. If insulin is not present in sufficient quantity, or if tissues have become resistant to insulin due to overeating, lack of exercise, or obesity, then hyperglycemia is the result. A consistently high level of glucose in the bloodstream can damage the heart, blood vessels, kidneys, and nerves, and increases the risk of cataract. There are many effective medications now available for the treatment of diabetes, and new therapies that are being developed and being released on a yearly basis. Following is a summary of the mechanisms of action of the mainstay medications, as well as some of the new medications available: Metformin works by decreasing hepatic glucose output, glipizide and glimepiride by increasing insulin release from the pancreas, and pioglitazone by increasing the sensitiviy of cells to insulin. Newer medications work more indirectly, such as exenatide, which mimics endogenous compounds that potentiate gluocose-stimulated insulin secretion, and sitagliptin, which inhibits the breakdown of enzymes involved in stimulating insulin release. Pramlintide is a new medication that mainly affects glucose levels after eating, referred to as post-prandial glucose. The goal of therapy is to reduce the hemoglobin A1c, a measure of the average amount of glucose in the blood over a period of 2 or 3 months, to less than 7%. This has shown to significantly reduce the risk of micro- and macrovascular complications. The ADA’s recent Consensus Statement provides recommendations on the most effective therapies and combinations in light of the many new and old medications now available for diabetes. Among the first tier, well-validated core initial therapies that are recommended are lifestyle changes to decrease weight and increase activity, and metformin. Weight loss, if maintained, is the most cost-effective means of controlling diabetes, in addition to improving cardiovascular risk factors such as blood pressure and high cholesterol that are often present in diabetic patients. Nevertheless, metformin is recommended alongside lifestyle changes as initial therapy, since these changes can be hard to make or maintain for many patients. Metformin is usually titrated by beginning with 500 mg daily or twice daily, moving up to 1000 mg twice daily after 5 to 7 days if gastrointestinal side effects have not occurred. The maximum effective dose is often 850 mg twice daily. These two therapies each have the potential of decrease the A1c 1. 0 to 2. 0%. Metformin is used as step 1 therapy for its low level of side effects compared with the step 2 therapies insulin and sulfonylureas (glipizide and glimepiride), as well as a high level of acceptance and relatively low cost. Insulin, on the other hand, requires daily injections and monitoring, and like sulfonylureas, carries the side effects of weight gain increased risk of hypoglycemia. Nevertheless, these therapies are just as effective if not more so (in the case of insulin) in controlling diabetes and are recommended as the next line of therapy when the target A1c level is not achieved. For more detailed information, you can refer the Consensus Algorithm at http://care. diabetesjournals. org/misc/MedicalManagementofHyperglycemia. pdf. Patients who would like to have their medications reviewed by a pharmacist can contact senior care pharmacists, who specialize in optimizing a patient’s medications to increase effectiveness, reduce pill burden, decrease cost, and mitigate or eliminate side effects.