Pharmacokinetic and pharmacodynamic differences of new generation, longer-acting basal insulins: potential implications for clinical practice in type 2 diabetes.

The treatment of type 2 diabetes (T2D) is often complicated by factors such as patient co-morbidities, complex drug-drug interactions, and management of adverse events. In addition, some of these factors are highly dependent on the nature of the treatment regimen and the molecular and physical properties of the drugs being used to treat patients with this disease. This calls for a better understanding of how the properties of individual drugs affect the overall outcome for patients with diabetes. Clinical pharmacology studies to assess the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of new diabetes drugs play an important role in advancing our understanding of the interactions between a drug and the human body. Specific PK and PD techniques such as the glucose clamp test can be applied to assess the properties of drugs used for the treatment of diabetes. Basal insulin analogs are a common treatment option for the maintenance of glycemic control in patients with T2D. These drugs work by mimicking endogenous insulin secretion within the body and provide stable and prolonged insulin action to achieve optimal glucose levels. Insulin glargine 300 U/mL (Gla-300) and insulin degludec (IDeg) 100 U/mL and 200 U/mL represent a new generation of longer-acting basal insulins. These drugs demonstrate improved PK and PD properties compared with previous basal insulins, allowing them to more closely mimic physiological basal insulin secretion. Here we review the methods used to evaluate the PK and PD profiles of Gla-300 and IDeg and describe studies that have investigated the PK/PD properties of these drugs in type 1 diabetes. The aim of this review is to inform primary care physicians of the value and limitations of data from clinical pharmacology studies when prescribing these agents for the management of T2D.

Insulin therapy in type 2 diabetes mellitus: a practical approach for primary care physicians and other health care professionals.

The responsibility of diabetes management and insulin therapy has definitively moved to primary care physicians. Within the primary care setting, there is a growing need for clear, evidence-based guidelines related to the management of insulin therapy. Straightforward algorithms regarding insulin initiation, titration, and follow-up management can help physicians effectively treat patients with type 2 diabetes mellitus. Once 2 oral diabetic drugs have failed in a patient whose disease duration is 7 to 10 years, use of insulin therapy with a basal insulin analog should be considered. For patients who receive maximal basal insulin doses without reaching fasting blood glucose and target glycated hemoglobin levels with basal insulin analogs, a mealtime-insulin intensification approach should be considered. The authors discuss how simplified insulin initiation and titration regimens allow primary care physicians and other health care professionals to care for patients with type 2 diabetes mellitus.

Empowering patients during insulin initiation: a real-world approach.

Glycemic control is suboptimal in many patients with type 2 diabetes mellitus (T2DM). Despite documented benefits of insulin therapy, initiation of insulin is delayed in many cases because of the reluctance of patients and physicians to use this important treatment. A review of the literature revealed that educating patients about the role of insulin in managing T2DM and the advantages of using insulin analogs and insulin delivery devices may help alleviate some patients' concerns regarding insulin therapy. Compared with standard clinic-directed approaches, patient-driven algorithms that empower patients to initiate and titrate basal insulin therapy have been shown to improve glycemic control. Additional research is needed to confirm the importance of patient empowerment programs in T2DM management.

Reaching HbA1c goals with saxagliptin in combination with other oral antidiabetic drugs.

A large percentage of individuals with type 2 diabetes in the United States are not reaching their glycemic goals. In response to data from large outcomes trials and newer classes of therapeutic agents, various organizations and opinion-forming bodies recently updated their clinical practice recommendations for type 2 diabetes. The recommendations, as set by the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD), the American Association of Clinical Endocrinologists/American College of Endocrinology, and the Canadian Diabetes Association, are similar in their emphasis on lifestyle modification and the importance of treating fasting and postprandial glucose, both of which are significant contributors to achieving glycated hemoglobin (HbA1c) targets. However, the recommendations differ in focus, depth, and specific treatment approaches. With the exception of the ADA/EASD consensus, dipeptidyl peptidase-4 (DPP-4) inhibitors have been included as alternative first- or second-line therapy due, in part, to their glucose-dependent mechanism of action that complements the actions of other oral antidiabetic drugs (OADs). The DPP-4 inhibitor, saxagliptin, demonstrates significant glycemia-lowering effects as monotherapy and in combination therapy, is weight neutral and well tolerated, and has a low risk of hypoglycemia. The added efficacy of saxagliptin in combination with other OADs in improving glycemic parameters has resulted in a significant proportion of patients achieving an HbA1c <7% versus monotherapy or active comparator. Combination therapy with saxagliptin can thus offer a potential advantage in achieving glycemic goals for the majority of patients with type 2 diabetes without additional tolerability concerns.

Oral combination therapy with thiazolidinediones in type 2 diabetes.

Insulin resistance occurs early in the type 2 diabetes disease process, leading to progressive beta cell failure and overt diabetes. By the time the diagnosis of diabetes is made, advanced macrovascular disease may already be present. Monotherapy with a sulfonylurea or metformin can slow, but does not prevent, the progression of disease. Successful management requires combination therapy that addresses both insulin resistance and beta cell dysfunction. Clinical trials support the use of combinations of agents with complementary mechanisms of action, such as a sulfonylurea or metformin plus a thiazolidinedione. Early aggressive treatment can improve patient outcomes while reducing overall healthcare costs.