Impact of improving postprandial glycemic control with intensifying insulin therapy in type 2 diabetes.

Worldwide, many people with type 2 diabetes are not at recommended glycemic targets and remain at increased risk of microvascular and macrovascular complications. Reaching recommended glycemic targets requires normalizing both fasting and postprandial glucose (PPG). For some patients, this will require addition of a prandial insulin delivered by injection to control PPG excursions. Evidence from epidemiological studies suggests an association between postprandial hyperglycemia and cardiovascular disease, and thus, expert guidelines recommend that treatment for elevated PPG not be delayed. Indeed, studies have demonstrated that PPG makes the greatest contribution to HbA1c in patients who are approaching, but have not yet reached HbA1c <7.0%. Appropriately timed exposure of the liver to insulin is critical in suppressing hepatic glucose output (and therefore PPG levels) after a meal. Rapid-acting insulin analogs, with their faster onset and shorter duration of action, offer advantages over regular human insulin. Unfortunately, even with improved pharmacokinetic/pharmacodynamic characteristics, rapid-acting insulin analogs are still unable to fully reproduce the rapid release of insulin into the portal circulation and suppression of hepatic glucose output that occurs in the individual without diabetes after starting a meal. The next generation of rapid-acting insulin analogs will have an even more favorable pharmacokinetic profile that should allow patients to further improve glycemic control. Continuous subcutaneous insulin infusion (CSII) represents another option for intensifying therapy and improving postprandial control in some patients, and studies have shown that the benefits are sustainable long-term. However, it is currently unclear which patients stand to benefit the most from the extra expense and complexity of a CSII regimen, and further studies are needed.

Dapagliflozin combination therapy in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a progressive disease, and most patients ultimately require two or more antidiabetes drugs in addition to lifestyle changes to achieve and maintain glycemic control. Current consensus statements and guidelines recommend metformin as first-line pharmacotherapy for the treatment of T2DM in most patients. When glycemic control cannot be maintained with metformin alone, the sequential, stepwise addition of other agents is recommended. Agents such as thiazolidinediones or sulfonylureas have typically been added to metformin therapy. Although effective in reducing glycated hemoglobin, these drugs are often associated with adverse effects, most notably weight gain, and in the case of sulfonylureas, hypoglycemia. Sodium-glucose cotransporter 2 inhibitors, such as dapagliflozin, are the newest class of antidiabetes drugs approved for the treatment of T2DM. Dapagliflozin effectively improves glycemic control by increasing the renal excretion of excess glucose. In clinical trials, dapagliflozin has been well tolerated and has additional benefits of weight loss, low risk of hypoglycemia and reduction in blood pressure. This review discusses the clinical evidence and rationale for the use of dapagliflozin as add-on therapy in T2DM. The results suggest that dapagliflozin add-on therapy is a promising new treatment option for a wide range of patients with T2DM. Results from an ongoing cardiovascular outcomes trial are needed to establish the long-term safety of dapagliflozin.

Combining clinical judgment with guidelines for the management of type 2 diabetes: overall standards of comprehensive care.

The rising toll of type 2 diabetes mellitus (T2DM) on patients and society has resulted in a wide variety of guidelines and therapies to address the need to combat this trend. Given the heterogeneity of T2DM and the different responses patients have to therapies, as well as the continued need for patients to institute lifestyle changes, guidelines published by the American Diabetes Association/European Association for the Study of Diabetes and the American Association of Clinical Endocrinologists/American College of Endocrinology have in recent years increased the focus on personalized and patient-centered care. How to best assimilate the overall standards of care for T2DM into clinical practice remains a challenge. The 4 pillars of effective diabetes management are a unifying framework and approach to clinical practice that can be integrated with the latest diabetes guidelines. These 4 pillars are lifestyle modifications involving (1) diet, (2) exercise, (3) a system to monitor preprandial and postprandial blood glucose and glycated hemoglobin levels, and (4) pharmacologic intervention when required. This article reviews the overall standards of care for T2DM, focusing on the first 3 nonpharmacologic pillars, and provides suggestions for integrating this approach with the current American Diabetes Association and American Association of Clinical Endocrinologists/American College of Endocrinology guidelines. Barriers to effective implementation of exercise programs, diets, and monitoring of blood glucose levels are discussed along with clinical strategies to overcome these barriers and achieve effective glycemic control and lifestyle changes for patients with T2DM. Personalized approaches to the management of T2DM are also reviewed.

Application of clinical judgment and guidelines to achieving glycemic goals in type 2 diabetes: focus on pharmacologic therapy.

Successful management of patients with type 2 diabetes mellitus requires attention to 4 pillars of care: diet, exercise, blood glucose monitoring, and pharmacologic therapy. For pharmacologic therapy, the availability of multiple drugs in different classes can make choices regarding initiation and intensification of treatment challenging. This article, focusing on clinical practice, reviews and provides guidance on assessing recommendations made by the latest diabetes guidelines for pharmacotherapy published by the American Diabetes Association and the American Academy of Clinical Endocrinologists. The article discusses how diabetes guidelines evolved, their move toward personalization of therapy, and their effective use in clinical practice. An appraisal of various pharmacologic strategies is integrated with the author's approach to achieving glycemic goals with a minimum of weight gain or hypoglycemic episodes. Using patients' baseline glycated hemoglobin levels and the degree to which their fasting and postprandial plasma levels contribute to their hyperglycemia is explained as a strategy by which drugs can be chosen that act on these parameters. Lifestyle interventions such as diet and exercise should continue to form the foundation of the therapeutic alliance between the clinician and patient as pharmacologic therapy is initiated or intensified.