Christopher D Saudek, MD
Dr Saudek joked that if you’ve been out of medical school for more than 6 months, you are no longer up to date on diabetes treatments. Two new types of diabetes medications have recently become available, incretin mimetics and inhaled insulin. Additionally, progress has been made on continuous glucose monitors, and we are closer to the advent of closed-loop insulin infusion systems. Dr Saudek noted that glucagon-like peptide-1 (GLP-1) is an intestinal hormone that modulates numerous functions in humans: it enhances glucose-dependent insulin secretion, slows gastic emptying, and acts on the CNS to promote satiety and reduce appetite. Exenatide is a GLP-1 analog that has a longer half-life than native GLP-1 because it is resistant to degradation by dipeptidyl peptidase IV (DPP-IV). Patients treated with exenatide in Phase III clinical trials had statistically significant reductions in A1C and body weight compared to patients treated with placebo, although nausea was significantly more likely in exenatide-treated patients. Exenatide is supplied as a parenteral injection packaged in prefilled pen injectors. DPP-IV inhibition slows the clearance of endogenous incretins. Sitagliptin is the first FDA-approved DPP-IV inhibitor and is administered orally. DPP-IV inhibitors have a significant but modest effect on A1C reduction and are weight-neutral. Currently, it is unclear how exenatide and DPP-IV inhibitors will coexist in the therapeutic armamentarium.
It has long been known that insulin can cross the pulmonary epithelium, and the large surface area of the lungs—approximately equal to a football field—suggests that insulin administered by inhalation offers the advantages of rapid and efficient drug administration while avoiding first-pass clearance by the liver and avoiding the need for injections. The A1C reductions reported for inhaled insulin are comparable to subcutaneous regular insulin. However, the size and convenience of the insulin inhaler are a concern. Contraindications to the use of dry powder inhaled insulin include asthma, chronic obstructive pulmonary disease, and smoking or smoking cessation within the past 6 months. Patients treated with inhaled insulin have lower rates of hypoglycemia and weight gain than with subcutaneous regular insulin. While no long-term effects on pulmonary function have been observed in patients with normal lung function, measurement of pulmonary function while being treated with inhaled insulin is required.
Even 5-times daily fingerstick glucose monitoring does not necessarily reveal the full range of glucose fluctuations over a day. Continuous glucose monitoring (CGM) provides a lot of information not available from routine monitoring, such as peaks, nadirs, and trends in glycemic variation. The GlucoWatch G2 Biographer is a CGM system that received most of the press attention a few years ago. The Biographer was worn on the arm, but patients complained of skin irritation and of being able to feel the electrical current used to permit the reverse iontophoresis by the sensor. This device is no longer on the market. The CGMS System God was FDA-approved in 2005. It uses a belt-worn receiver and a sensor that is replaced every 3 days that is worn on the skin of the abdomen. Patients have found this device more comfortable to wear than the Biographer, but because the device must be calibrated with a fingerstick 4 times a day, patients don’t perceive much of an advantage from using it. The FreeStyle Navigator is a CGM system currently under FDA review. The sensor for the Navigator may be worn on the arm or the abdomen. Sensors in other systems transmit glucose wirelessly transmit data to an insulin pump, although they do not drive the pump. Efforts toward a closed-loop insulin delivery system have been made. These systems consist of an intravenous glucose sensor, and implantable pump, and a data communication link.
|
