The Effect of Prestudy Insulin Therapy on Safety and Efficacy of Human Regular U-500 Insulin by Pump or Injection: A Posthoc Analysis.

OBJECTIVE: We conducted a posthoc analysis of the VIVID study (Safety and Efficacy of Human Regular U-500 Insulin Administered by Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections in Subjects With Type 2 Diabetes Mellitus: A Randomized, Open-Label, Parallel Clinical Trial), comparing 2 delivery methods of human regular U-500 insulin (U-500R), continuous subcutaneous insulin infusion (CSII) versus multiple daily injection (MDI), in type 2 diabetes requiring high insulin, to determine influence of prestudy insulin on glycemic outcomes. METHODS: We compared A1C, total daily insulin dose (TDD), weight, and hypoglycemia by subgroups of prestudy insulin (prestudy U-500R vs non-U-500R) and treatment (CSII vs MDI). RESULTS: At baseline, prestudy U-500R had higher TDD, higher body mass index, lower A1C and fasting plasma glucose, and higher rate of hypoglycemia compared to non-U-500R. Active titration of U-500R reduced A1C in both subgroups, with maximum benefit at 8 weeks. At 26 weeks, CSII provided the greatest reduction in A1C in both subgroups, with a greater reduction in non-U-500R. MDI provided an A1C reduction in both subgroups, with the greater reduction in non-U-500R. At 8 weeks, prestudy U-500R reached its lowest A1C; thereafter, A1C rebounded with MDI and remained stable with CSII. In non-U-500R, A1C continued to decrease to study end. In non-U-500R, hypoglycemia increased during active titration, but then decreased in the posttitration maintenance period. In both subgroups, TDD increased from baseline with MDI but not with CSII. Body weight increased in both subgroups but was greater in prestudy U-500R with CSII compared to MDI. CONCLUSION: Regardless of previous insulin, people on high-dose insulin could lower A1C with U-500R, with additional benefit from CSII. These results may provide guidance for use of U-500R in clinical practice.

BIOSIMILARS AND NEW INSULIN VERSIONS.

OBJECTIVE: To provide clinicians with an overview of similar biologic products including biosimilars and new insulin versions available in the U.S. and of key issues associated with such products, including differences in manufacturing and regulatory approaches and their impact on clinical use. METHODS: We reviewed the relevant clinical and regulatory literature. RESULTS: Patent protections for many biologics including several insulin preparations have or will expire shortly. This opens the door for new insulin versions to enter the U.S. and global marketplace. The development, manufacturing, and approval process for similar biologic products is more complex than for generic versions of small molecules. Most similar biologic products in the U.S. will be submitted for approval under section 351(k), a newly created biosimilar regulatory pathway. However, some biologics, including new insulin versions, will be submitted via the existing 505(b)(2) regulatory pathway. These regulatory pathways have implications for how such products may be labeled, how they may be dispensed, and how patients may perceive them. The immunogenicity of biologics can affect safety and efficacy and can be altered through subtle changes in manufacturing. With the arrival of new insulin versions, health care providers will need to understand the implications of interchangeability, therapeutic equivalence, substitution, switching, and new delivery devices. CONCLUSION: An understanding of the above topics will be important as physicians, payers, and patients choose between similar versions of a reference listed biologic product.

Optimizing inpatient glycemic control with basal-bolus insulin therapy.

Hyperglycemia is highly prevalent in the acute-care setting and is associated with an increased risk of morbidity and mortality. Evidence suggests that glycemic control in this population is suboptimal, due in part to continued use of nonphysiologic sliding-scale insulin strategies without scheduled basal insulin doses or prandial insulin with concomitant correction doses. Although the ineffectiveness and risks of sliding-scale insulin regimens have been criticized for decades, sliding-scale insulin is still the most commonly prescribed subcutaneous insulin regimen among inpatients. Improving inpatient management requires the use of scheduled basal-bolus insulin therapy that includes basal insulin, nutritional insulin, and supplemental, or correctional, insulin. Insulin analogs are the preferred insulins, as they provide a more physiologic action than human insulin regimens, are associated with a lower risk of hypoglycemia, and are more convenient to administer than human insulins. Standardized insulin protocols and subcutaneous insulin order sets are critical components of effective inpatient glycemic control. Although preliminary data have demonstrated that inpatient diabetes management programs involving basal-bolus insulin therapy are effective and well tolerated, more research is needed.

Utilization of a multidisciplinary team for inpatient diabetes care.

Diabetes is often noted as a secondary diagnosis when patients are admitted to the hospital for care. Patients admitted to critical care areas are usually more ill and require aggressive glucose control. Often the education and self-care management skills needed for home management are overlooked until discharge, which can cause an increased length of stay. There is a feeling of frustration among nurses who are unable to adequately meet the needs of these patients and their families. In one community hospital setting, they have designed a model that identifies patient needs on admission and utilizes a multidisciplinary team. Beginning the "discharge" process early in the admission will ensure that a timely discharge with a well-trained patient will occur.