Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are attractive options for the treatment of type 2 diabetes (T2D) because they effectively lower A1C and weight while having a low risk of hypoglycemia. The GLP-1 RA class has grown in the last decade with several agents available for use in the US and Europe and several more in development. Since the efficacy and tolerability, dosing frequency, administration requirements, and cost may vary between agents within the class, each agent may offer unique advantages and disadvantages. Through a review of phase III clinical programs for exenatide twice daily, exenatide once weekly, liraglutide, albiglutide, lixisenatide, and dulaglutide, eight head-to-head trials have evaluated the safety and efficacy of GLP-1 RA active comparators. The purpose of this review is to provide an analysis of these trials. The GLP-1 RA head-to-head clinical studies have demonstrated that all GLP-1 RA agents are effective therapeutic options at reducing A1C. However, differences exist in terms of magnitude of effect on A1C and weight as well as frequency and severity of adverse effects.

We review the last 18 months of literature on obesity, insulin resistance, and T1DM to highlight new epidemiologic results and treatments.

LOIS JOVANOVIC, MD 2OBJECTIVE -Hypoglycemia and wide glucose excursions continue to be major obstacles to achieving target HbA 1c values and the associated reductions in long-term complications (and economic costs) in people with insulin-treated diabetes. In this study we evaluated the accuracy, safety, and clinical effectiveness of a continuous glucose-sensing device. RESEARCH DESIGN AND METHODS-A total of 91 insulin-requiring patients with type 1 (n ϭ 75) and type 2 (n ϭ 16) diabetes were enrolled in this multicenter randomized study. Subjects wore a transcutaneous, 3-day, continuous glucose-sensing system for three consecutive 72-h periods. Subjects were randomly assigned (1:1 ratio) to either a control group (continuous glucose data not provided) or a display group (continuous glucose data not provided during period 1 but displayed during periods 2 and 3). During periods 2 and 3, patients in the display group had real-time access to sensor glucose values, could review glucose trends over the preceding 1, 3, and 9 h, and were provided with high (Ն200 mg/dl) and low (Յ80 mg/dl) alerts and a low (Յ55 mg/dl) alarm. Sensors were inserted by patients, and both groups used (or wore) the system during daily activities. Device accuracy was assessed by comparing continuous glucose values to paired self-monitoring of blood glucose (SMBG) meter readings. Clinical effectiveness was evaluated by analyzing between-group (control vs. display, periods 2 and 3) and within-group (display, period 1 vs. period 3) differences in time spent in high, low, and target (81-140 mg/dl) glucose zones.RESULTS -When prospective, real-time sensor values were compared with SMBG values, 95.4% of 6,767 paired glucose values fell within Clarke error grid A and B zones. Pearson's correlation coefficient was 0.88, and mean and median absolute relative differences were 21.2 and 15.9%, respectively. No systematic bias was detected at any of the prespecified glucose levels (50, 80, 100, 150, and 200 mg/dl). When compared with control subjects, the display group spent 21% less time as hypoglycemic (Ͻ55 mg/dl), 23% less time as hyperglycemic (Ն240 mg/dl), and 26% more time in the target (81-140 mg/dl) glucose range (P Ͻ 0.001 for each comparison). Nocturnal (10:00 P.M. to 6:00 A.M.) hypoglycemia, as assessed at two thresholds, was also reduced by 38% (Ͻ55 mg/dl; P Ͻ 0.001) and 33% (55-80 mg/dl; P Ͻ 0.001) in the display group compared with control subjects.CONCLUSIONS -We conclude that real-time continuous glucose monitoring for periods up to 72 h is accurate and safe in insulin-requiring subjects with type 1 and type 2 diabetes. This study demonstrates that availability of realtime, continuously measured glucose levels can significantly improve glycemic excursions by reducing exposure to hyperglycemia without increasing the risk of hypoglycemia, which may reduce long-term diabetes complications and their associated economic costs. Diabetes Care 29:44 -50, 2006I ntensive insulin therapy delays and prevents the progression of microvascular disease in p...

Sitagliptin significantly improved overall glucose control, including postprandial and 24-h glucose control, in adult patients with Type 1 diabetes, while significantly reducing prandial insulin requirements. Further investigation is warranted in patients with Type 1 diabetes in a larger cohort designed to assess both clinical outcomes and mechanism of action.