Barry Ginsberg

Intradermal Microneedle Delivery of Insulin Lispro Achieves Faster Insulin Absorption and Insulin Action than Subcutaneous Injection

BACKGROUND This study compared insulin lispro (IL) pharmacokinetics (PK) and pharmacodynamics (PD) delivered via microneedle intradermal (ID) injection with subcutaneous (SC) injection under euglycemic glucose clamp conditions. METHODS Ten healthy male volunteers were administered 10 international units (IU) of IL at 3 microneedle lengths (1.25, 1.50, or 1.75 mm) in a randomized, crossover fashion on Days 1-3 followed by a repetitive ID 1.5-mm microneedle dose (Day 4) and an SC dose (Day 5). RESULTS Microneedle ID delivery resulted in more rapid absorption of IL, with decreased time to maximum insulin concentration (ID vs. SC: 36.0-46.4 vs. 64.3 min, P < 0.05) and higher fractional availability at early postinjection times. ID produced more rapid effects on glucose uptake with shorter times to maximal and early half-maximal glucose infusion rates (GIRs) (ID vs. SC: time to maximum GIR, 106-112 vs. 130 min, P < 0.05; early half-maximal GIR, 29-35 vs. 42 min), increased early GIR area under the curve (AUC), and faster offset of insulin action (shorter time to late half-maximal GIR: 271-287 vs. 309 min). Relative total insulin bioavailability (AUC to 360 min and AUC to infinite measurement) did not significantly differ between administration routes. ID PK/PD parameters showed some variation as a function of needle length. Delivery of ID IL was generally well tolerated, although transient, localized wheal formation and redness were observed at injection sites. CONCLUSIONS Microneedle ID insulin lispro delivery enables more rapid onset and offset of metabolic effect than SC therapy and is safe and well tolerated; further study for insulin therapy is warranted.

Staged Diabetes Management: Computerizing a Disease State Management Program

Recently, the Diabetes Control and Complications Trial (DCCT) and other similar studies have demonstrated that near-normalization of blood glucose in diabetes will reduce complications up to 75% but translation of these results into practice has been difficult. In an attempt to help provide the best possible control of patients with diabetes, we have produced a new disease state management system for diabetes, called “Staged Diabetes Management” (SDM), implemented it in over 100 sites worldwide, and developed a computer program to simplify its use. SDM, designed to change the way we deal with patients with diabetes, is based upon five principles: (1) community involvement in setting care guidelines; (2) negotiation of goals with patients; (3) appropriate timelines for therapeutic success; (4) use of flowcharts for medical decisions; and (5) evaluation of the program. SDM is designed to be altered by a community to meet its needs and resources. It encourages primary care physicians to deliver better diabetes care using a team approach and to refer patients with diabetes to specialists when appropriate. It has a complete set of materials for communities, individual health care providers and patients. SDM has been tested for changes in structure, process and outcomes. A meta-analysis of seven clinical trials with over 500 patients has shown a time-weighted average fall in hemoglobin Alc of 1.7 points (equivalent to a drop in mean blood glucose of about 3.5 mM or 60 mg/dL). Preliminary pharmacoeconomic analysis demonstrates a lifetime cost saving of over

Patch Pumps: Are They All the Same?

27,000 per patient. A computer program has been developed for the Microsoft Windows® environment that contains a client-server database, based upon DiabCare, for the data file structure.

System for determining insulin dose using carbohydrate to insulin ratio and insulin sensitivity factor

Insulin pumps are used by a steadily increasing number of patients with diabetes. Avoiding certain disadvantages of conventional pumps (ie, the insulin infusion set) might make pump therapy even more attractive. Patch pumps are usually attached by means of an adhesive layer to the skin and have several additional advantages (smaller, more discrete, easier to use, and cheaper than conventional insulin pumps). This review provides a general overview of patch pumps, the technologies used, basic clinical requirements, why a number of developments failed, which clinical studies are needed to provide sufficient evidence for their usage, which costs are associated, what the patient preferences are (which might differ between certain patient groups), and what is the future of patch pumps (ie, artificial pancreas systems).