Our data demonstrate the effectiveness of pharmaceutical care in the reduction of hyperglycemia associated with NIDDM in a group of urban African-American patients.

T ype 2 diabetes has become a worldwide epidemic 1 and is associated with multiple complications that can be prevented by modifying risk factors and optimizing glycemic control. 2 The optimization of glycemic control often requires the use of multiple agents, including insulin.Insulin is an important component of antihyperglycemic therapy, yet there are many perceived barriers.3 Existing guidelines do not specifically address the topic of insulin initiation. 4 We review and analyze the evidence from randomized controlled trials on insulin initiation and address adverse effects and barriers. We also discuss the selection of an insulin regimen, titration and delivery of care, as well as when and how to combine insulin therapy with oral antihyperglycemic agents. A summary of our systematic review and meta-analysis is available in Box 1. When should insulin be started?Clinical practice guidelines vary as to the recommended criteria for the initiation of insulin therapy in pa tients with type 2 diabetes. Factors that are considered include the control of blood glucose levels and comorbidities that affect choice of treatment. Glucose controlThe American Diabetes Association and the European Association for the Study of Diabetes developed a consensus algorithm wherein basal insulin is recommended as a second-line agent if the glycated hemoglobin (HbA 1 c ) value is greater than 7.0% after metformin monotherapy.5 Similarly, the International Diabetes Federation recommends that insulin be started if optimized oral antihyperglycemic therapy and lifestyle interventions are unable to maintain blood glucose at target levels. 6 In contrast, the Canadian Diabetes Association recommends that insulin be considered as a first-line agent if the HbA 1c value is 9.0% or greater in pa tients with newly diagnosed diabetes or if there is symptomatic hyperglycemia with metabolic decompensation (defined as polyuria, polydipsia and weight loss), and as a second-line agent if the HbA 1c is still not at target levels (consensus recommendation). 4Although no randomized controlled trials have looked at the impact on cardiovascular outcomes of insulin initiation early in the course of type 2 diabetes, early intensive control of blood glucose levels was assessed in the United Kingdom Prospective Diabetes Study (UKPDS). The study compared intensive glycemic control (with metformin, secretagogue or insulin therapy) and conventional glycemic control in patients with newly diagnosed diabetes and found that those in the intensive treatment group had reduced microvascular and macrovascular complications in long-term follow-up. 7,8 Early insulin initiation has been shown to improve and preserve β-cell function, 9 and the ongoing Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial will assess the impact of an early basal insulin strategy on cardiovascular outcomes. 10 ComorbiditiesCareful monitoring of glycemic control is necessary when treating diabetes in patients with renal or hepatic failure. Many oral antihyperglycemic agents are c...

The pharmacokinetics and pharmacodynamics of glipizide were evaluated in 20 patients with non-insulin-dependent diabetes mellitus (NIDDM). The group consisted of 12 obese subjects (seven women, five men; mean +/- SD age, 53.5 +/- 8.5 years; total body weight (TBW), 95.5 +/- 17.2 kg; percentage > IBW (ideal body weight), 57.8 +/- 31.7%); and eight nonobese subjects (two women, six men; age, 57.8 +/- 11.7 years; TBW, 80.8 +/- 9.9 kg; percentage > IBW, 15.6 +/- 10.3%). After a 2-week antidiabetic drug-free period, patients were started on glipizide therapy for 12 weeks. Glipizide dosages were titrated to achieve specified therapeutic goals or a maximum daily dose of 40 mg. Glipizide pharmacokinetics were assessed by serum concentrations obtained during a 24-h pharmacokinetic evaluation performed after the first 5-mg dose (SD) and after 12 weeks of chronic therapy (CD). Glipizide pharmacodynamics were evaluated with serum glucose, insulin, and C-peptide responses to Sustacal tolerance test done at baseline, after SD, and after CD. No statistically significant differences in the SD pharmacokinetic parameters (Tmax = 3.1 +/- 1.2 vs. 2.8 +/- 1.6 h; Cmax = 332.5 +/- 92.5 vs. 420.8 +/- 142 g/L; area under the curve extrapolated to infinity (AUCI) = 2,598.3 +/- 1,148 vs. 3,138.9 +/- 1,847 g/h/L; oral clearance/bioavailability (CL/F), 2.3 +/- 1.0 vs. 2.0 +/- 1.0 L/h; volume of distribution/bioavailability (V/F), 19.5 +/- 4.4 vs. 17.2 +/- 4.3 L; t1/2 = 5.0 +/- 2.3 vs. 5.2 +/- 2.0 h) were observed between the obese and nonobese groups, respectively. The pharmacokinetic parameters assessed under CD conditions were also closely matched in the two groups. No differences in glucose responses to Sustacal challenge at baseline, SD, and CD (AUC0-->4.glucose:baseline, 52.3 +/- 18.0 vs. 44.9 +/- 9.8; SD, 50.4 +/- 20.9 vs. 36.1 +/- 11.0; CD, 37.8 +/- 10.7 vs. 36.6 +/- 8.5 mM/h) were noted between the obese and nonobese groups, respectively. However, glucose concentrations increased more and decreased to a smaller extent after SD in the obese as compared to nonobese subjects. Mean fasting serum insulin and C-peptide concentrations were not statistically different between the two groups. However, obese subjects exhibited higher fasting insulin (114.0 +/- 69 vs. 68.8 +/- 52 pM) at week 12 evaluation and C-peptide concentrations (0.83 +/- 0.2 vs. 0.63 +/- 0.2 nM) after SD as compared to the nonobese group. A smaller percentage increase in C peptide in response to Sustacal challenge was observed in the obese compared to the nonobese subjects (baseline, 60 +/- 25 vs. 117 +/- 117; SD, 119 +/- 39 vs. 193 +/- 149; and CD, 97 +/- 56 vs. 163 +/- 67%). In summary, the influence of obesity on glipizide pharmacokinetics appeared to be of little clinical significance. The observed differences in pharmacodynamics require further evaluation.