Frequency Of Hypoglycemic Events Research Articles

Duration of diabetes and effectiveness of insulin in the management of insulin-naïve Korean patients uncontrolled on oral antidiabetic drugs: a sub-analysis of the MOdaliTy of Insulin treatment eValuation (MOTIV) registry results

To investigate whether duration of diabetes has an impact on the effectiveness of insulinization in diabetes management. This open-label, noninterventional, observational registry was conducted at >500 centers in Korea. Patients with diabetes, on oral antidiabetic drugs, with HbA1c ≥7% (53mmol/mol) in the preceding 3months, being considered for initiation of basal insulin by their physicians, were included. Data were collected at baseline and at 3 and 6months. Of 6,616 patients evaluated, 62.5% had diabetes for <10years, while only 6.5% patients had diabetes for ≥20years. At the end of study, average HbA1c in patients with diabetes for <10years, for 10 to <20years, and for ≥20years was 7.3±1.0% (56±10.9mmol/mol), 7.4±1.0% (57±10.9mmol/mol), and 7.6±1.1% (60±12.0mmol/mol), respectively. Over half the patients (50.7%) with diabetes <10years achieved HbA1c <7% (53mmol/mol) by the end of study, while only 42.1 and 35.1% patients with diabetes for 10 to <20 and ≥20years, respectively, achieved their target. The average insulin dosage required for per unit HbA1c reduction was significantly different among the groups according to duration of type 2 diabetes mellitus (p<0.05). Among patients who achieved HbA1c <7%, proportion of patients with hypoglycemia in the ≥20years group was higher than that in the <10years, 10 to <20years groups. Early insulin administration provided a better glycemic control with less insulin dosage and lower frequency of hypoglycemic events. Thus, early insulinization might hold the key to better management of type 2 diabetes mellitus.

Improving the Estimation of Meal-Time Insulin Dose Based On the Glycaemic Load of a Meal in Children with Type 1 Diabetes on Insulin Pump Therapy: A Randomized Study

Background: The aim of the study was to assess whether an Insulin-Carbohydrate Ratio (ICR) increased by 30% per meal with a high glycaemic load allows postprandial glucose excursion to be maintained in control in children with type 1 diabetes. Methods: A total of 70 children on insulin pump therapy participated in the study. They were stratified into age groups: 4-7 years of age, 8-12 years of age and above 12 years of age. The experimental Group (A) received an insulin dose based on individualised ICR increased by 30% for breakfast containing cornflakes with milk. The control group (B) received an insulin dose based on standard individualised ICR. The glycaemic load of the meal was adjusted to the age group (24,3; 32,4; 40,5). We assessed metabolic effects such as the area under the glucose curve (AUC), glucose increment, risk of hyperglycaemia and hypoglycaemia using two methods: blood glucose concentration (at 0, 15, 30, 45, 60, 90 and 120 minutes) and a continuous subcutaneous glucose measurement system (for 3 hours postprandially). Results: A significant glucose rise was noted in the control group B (p=0.03). Over the postprandial 180 minutes, AUC was significantly lower (p=0.02) in the experimental group but only in children aged 8-12. The frequency of hypoglycaemic events was not statistically significant during postprandial observation (p=0.75). Conclusion: Increasing the ICR by 30% for a meal with high GL can reduce the glucose excursion without increasing the risk of hypoglycaemia in children with type 1 diabetes treated with insulin pump therapy.

Basal insulin therapy strategy is superior to premixed insulin therapy in the perioperative period blood glucose management

Background The probability and risk of operations increase in patients with type 2 diabetes mellitus. For diabetic patients, blood glucose control is a key factor to improving the prognosis of surgery. During perioperative period, insulin therapy is usually advised to be used for surgical patients with type 2 diabetes. However, the insulin regimen which one is better remains controversial. In this study, we estimated the efficacy, safety and advantage of different insulin therapy strategy during perioperative period. Methods A total of 1086 cases of surgical patients with type 2 diabetes mellitus enrolled in the present study. According to the glucose level at admission, all patients were divided into relatively high glucose group (group A, fasting blood glucose (FBG) ≤13.9 mmol/L) and higher glucose group (group B, FBG &gt;13.9 mmol/L). Patients in group A randomly accepted premixed insulin twice a day, or basal insulin plus oral medications, and were divided into group A1 and A2 respectively. Patients in group B randomly received premixed insulin twice daily, basal insulin plus oral hypoglycemic agents, or basal insulin plus preprandial insulin, and were divided into group B1, B2 and B3 respectively. The data of the preoperative preparation time, the daily doses of insulin used in different periods, postoperative incision healed installments, hypoglycemic events, the total hospitalization time, postoperative complications were all collected and statistically analyzed. Results Compared the main outcome measures in groups treated by premixed insulin therapy, both in preoperative preparation and postoperative period, the daily insulin dosage and the frequency of hypoglycemic events were decreased in groups treated by basal insulin therapy (P &lt;0.05). The preoperative preparation time and the total hospitalization time in groups with basal insulin therapy were shorter than that in groups with premixed insulin therapy (P &lt;0.05). The incision healing rate of stage I, II and III among different therapy protocols were significantly different (P&lt;0.05). Conclusions Basal insulin therapy could be used in diabetic patients undergoing elective major and medium surgery during whole perioperative period. Basal insulin therapy strategy, including a single injection of basal insulin and basal insulin plus preprandial insulin injection subcutaneously, is superior to premixed insulin therapy in the perioperative blood glucose management, and it could be viewed as the best choice in glucose control during perioperative period.

Learning About New Therapies: Phase 3 Clinical Studies—And Beyond

All new therapeutic agents, and updated versions of older ones, must be submitted for review by regulatory agencies. While this process is complex, its goals as stated by the U.S. Food and Drug Administration (FDA) are straightforward. The main aim is to determine “whether the drug is safe and effective in its proposed use(s), and whether the benefits of the drug outweigh the risks” (1). Additional concerns are the information provided in the package insert and assurance of quality and consistency of the manufacturing process. Phase 3 trials, which test the safety and efficacy of candidate drugs in moderately large cohorts of human subjects, lie at the center of the process. Properly done studies of this kind help determine whether a new product should be approved for clinical use and also provide some guidance regarding how best to use it in daily practice. However, phase 3 studies—as essential as they are to the regulatory process—have important limitations, which are the topic of this commentary. Appearing in this issue of Diabetes Care is a good example of such a study. Gough et al. (2) report a comparison of a 200 units/mL (U200) formulation of degludec, a long-acting insulin analog, with U100 insulin glargine (Lantus). The study was well designed and well conducted. The investigators enrolled 457 participants with type 2 diabetes no longer well controlled with oral therapies alone (mean A1C ∼8.2%), and randomized them to begin and titrate dosage of once-daily U200 degludec or U100 glargine using a typical treat-to-target scheme for 26 weeks. Efficacy of the new agent was assessed by the reduction of A1C from baseline, and its safety by, among other measurements, the frequency of hypoglycemic events. As in many studies, the main end point was noninferiority of glycemic improvement versus a well-known active comparator. The results …

Biosimilar Insulin and Insulin Antibodies

Biosimilar Insulin and Insulin Antibodies

A Retrospective Audit of Type 2 Diabetes Patients Prescribed Liraglutide in Real-Life Clinical Practice

BackgroundIn phase 3 trials, the once-daily human glucagon-like peptide-1 analog liraglutide provided effective glycemic control with low rates of hypoglycemia, weight loss, and reduced systolic blood pressure (SBP) in patients with type 2 diabetes. Through a retrospective clinical audit, the authors aimed to assess the clinical effectiveness of liraglutide, from initiation to first hospital visit, when prescribed at a center in Northern Ireland.MethodsPatients attending Ulster Hospital who were prescribed liraglutide (June 2009–September 2010) and assessed both at baseline and first post-initiation visit were included in the analysis. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline. Weight, blood pressure, and frequency of hypoglycemic events were also assessed.ResultsData from 193 patients are reported (baseline HbA1c 9.0%, mean age 55.8 years, diabetes duration 8.8 years, 66.8% male). Average time to first visit after initiation was 13.5 weeks, at which point 174 patients (90.2%) were prescribed 1.2 mg liraglutide. Mean change in HbA1c from initiation to first visit was −0.9%, while mean body weight change was −2.4 kg and change in SBP was −2.0 mmHg. Transient gastrointestinal side effects were experienced by 11.9% of patients. The number of patients experiencing minor hypoglycemic events was low (5.7%) and no major events were reported.ConclusionData from clinical studies translate into clinical practice: liraglutide provided improved glycemic control after 13.5 weeks of treatment, accompanied by weight loss and low incidence of hypoglycemia.

Pharmacotherapy in Type 1 Diabetes

Pharmacotherapy in Type 1 Diabetes

Cardiovascular disease and glycemic control in type 2 diabetes: now that the dust is settling from large clinical trials

The relationship between glucose control and cardiovascular outcomes in type 2 diabetes has been a matter of controversy over the years. Although epidemiological evidence exists in favor of an adverse role of poor glucose control on cardiovascular events, intervention trials have been less conclusive. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, the Action in Diabetes and Vascular Disease (ADVANCE) study, and the Veterans Affairs Diabetes Trial (VADT) have shown no beneficial effect of intensive glucose control on primary cardiovascular endpoints in type 2 diabetes. However, subgroup analysis has provided evidence suggesting that the potential beneficial effect largely depends on patients’ characteristics, including age, diabetes duration, previous glucose control, presence of cardiovascular disease, and risk of hypoglycemia. The benefit of strict glucose control on cardiovascular outcomes and mortality may be indeed hampered by the extent and frequency of hypoglycemic events and could be enhanced if glucose-lowering medications, capable of exerting favorable effects on the cardiovascular system, were used. This review examines the relationship between intensive glucose control and cardiovascular outcomes in type 2 diabetes, addressing the need for individualization of glucose targets and careful consideration of the benefit/risk profile of antidiabetes medications.

A discrete choice experiment evaluation of patients' preferences for different risk, benefit, and delivery attributes of insulin therapy for diabetes management

ObjectiveTo evaluate patients’ preferences for various attributes of insulin treatment, including route of insulin delivery.MethodsWe used a discrete choice experiment (DCE) to quantify patients’ preferences. The attributes (and levels) included in the DCE questionnaire were: glucose control, frequency of hypoglycemic events, weight gain, route of administration for the long-acting and the short-acting insulin, and out-of-pocket cost. Data were analyzed using conditional logit regression and segmented models were also developed to evaluate differences in preferences between subgroups.ResultsTwo hundred and seventy-four questionnaires were completed. The mean age (SD) of participants was 56.7 (12.9) years. Forty-nine percent of participants were insulin users, and 17% had type 1 diabetes. Overall, patients’ ideal insulin treatment would provide better glucose control, result in fewer adverse reactions, have the lowest cost, and be administered orally. Overall, there was a strong positive preference for better glucose control relative to the other attributes. Segmented analyses by insulin use and type of diabetes suggest that there may be an important psychosocial barrier to initiating insulin therapy but that patients tend to adjust to subcutaneous administration once they initiate therapy.ConclusionsThis study illustrates the importance that patients with diabetes place on glucose control and how preferences for insulin therapy differ between subgroups. Specifically, efforts need to be made to overcome the psychosocial barriers to initiating insulin therapy which may lead to improved control through improved treatment acceptance and ultimately improve patients’ quality of life and reduce the economic burden of the disease.

The importance of anti-insulin antibody in patients with type 1 diabetes mellitus treated with continuous subcutaneous insulin infusion or multiple daily insulin injections therapy

To investigate the influence of two insulin administration modalities, continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) therapy with insulin analogues, on the development of insulin antibodies (IAs) in patients with type 1 diabetes mellitus and to assess the impact of IAs on glucose control and hypoglycaemia. 96 patients with type 1 diabetes mellitus treated with CSII (n=48) or MDI (n=48) were included in the study. Age, duration of diabetes, A1c, preprandial and postprandial blood glucose and hypoglycaemic events were compared between IA positive and negative patients. IA levels were higher in the CSII group (% 24.6±14.2) than the MDI group (% 13.2±9.9). Duration of diabetes and age were not associated with IA positiveness. While A1c, preprandial blood glucose and the frequency of hypoglycaemic events were similar in two groups, postprandial blood glucose was lower in IA positive group (P=0.03). Patients with type 1 diabetes mellitus treated with CSII with insulin analogues had higher IA levels when compared to MDI therapy. However, the development of IAs did not impair the glycaemic control.

Preclinical and clinical studies on safety and tolerability of repaglinide.

Repaglinide, an insulinotropic benzoic acid derivative, has been tested extensively in the preclinical and clinical setting for safety and tolerability. In preclinical safety trials, no clinically relevant laboratory or histopathological changes were found and repaglinide was not found to be genotoxic, immunogenic, teratogenic or tumorigenic at levels 50 times greater than the exposure in humans. In an ascending-dose tolerability study in Type 2 diabetic patients, no clinically relevant changes in liver enzymes or ECG occurred during the trial. A total of five active-controlled, long-term trials of identical design have been carried out (with 12 months of maintenance on a fixed, pretitrated dose), including 1228 patients on repaglinide and 597 on sulphonylureas, 417 of whom were on glibenclamide. The most common adverse event in the phase II studies was hypoglycaemia. The frequency of hypoglycaemia was identical for repaglinide and sulphonylureas; however, fewer nocturnal hypoglycaemic events were observed with repaglinide and no increase in the frequency of hypoglycaemic events occurred in elderly patients (> 65 years) compared with younger patients. Severe reactions (assistance required) were approximately twice as frequent in the comparator group. During these studies, two serious hypoglycaemic reactions were reported (coma, seizure or hospitalization), both occurring in patients on glibenclamide. The frequency of serious adverse events and serious cardiovascular events was comparable between repaglinide and sulphonylureas.

Comparison of Inpatient Insulin Regimens with Detemir plus Aspart Versus Neutral Protamine Hagedorn plus Regular in Medical Patients with Type 2 Diabetes

Studies comparing the use of basal bolus with insulin analogs vs. split-mixed regimens with human insulins in hospitalized patients with type 2 diabetes are lacking. In a controlled multicenter trial, we randomized 130 nonsurgical patients with blood glucose (BG) between 140 and 400 mg/dl to receive detemir once daily and aspart before meals (n = 67) or neutral protamine Hagedorn (NPH) and regular insulin twice daily (n = 63). Insulin dose was started at 0.4 U/kg.d for BG between 140 and 200 mg/dl or 0.5 U/kg.d for BG 201-400 mg/dl. Major study outcomes included differences in mean daily BG levels and frequency of hypoglycemic events between treatment groups. Glycemic control improved similarly in both groups from a mean daily BG of 228 +/- 54 and 223 +/- 58 mg/dl (P = 0.61) to a mean daily BG level after the first day of 160 +/- 38 and 158 +/- 51 mg/dl in the detemir/aspart and NPH/regular insulin groups, respectively (P = 0.80). A BG target below 140 mg/dl before meals was achieved in 45% of patients in the detemir/aspart group and 48% in the NPH/regular group (P = 0.86). During treatment, 22 patients (32.8%) in the detemir/aspart group and 16 patients (25.4%) in the NPH/regular group had at least one episode of hypoglycemia (BG < 60 mg/dl) during the hospital stay (P = 0.34). Treatment with basal/bolus regimen with detemir once daily and aspart before meals results in equivalent glycemic control and no differences in the frequency of hypoglycemia compared to a split-mixed regimen of NPH and regular insulin in patients with type 2 diabetes.

Efficacy of continuous subcutaneous insulin infusion in Type 1 diabetes: a 2‐year perspective using the established criteria for funding from a National Health Service

To determine the 2-year efficacy of continuous subcutaneous insulin infusion (CSII) following the current established criteria for funding of a National Health Service. Longitudinal, prospective, observational unicentre study. Included in the study were 153 Type 1 diabetes (T1D) subjects, previously treated with multiple daily injections (MDI) of insulin, in whom CSII was started in accordance with the criteria for reimbursement of the Catalan National Health Service. At baseline, we recorded data on age, gender, duration of the disease, body mass index (BMI), insulin dose and indications for CSII. Glycated haemoglobin (HbA(1c)) and the frequency of hypoglycaemic events were used to assess glycaemic control. Quality of life was assessed using three different self-report questionnaires. After 24 months, these same items were remeasured in all subjects. Serious adverse events and injection-site complications were also recorded. In 96% of subjects, CSII indication included less than optimal glycaemic control using MDI. HbA(1c) fell from 7.9 +/- 1.3 to 7.3 +/- 1.1% (P < or = 0.001) after 24 months of CSII. Insulin requirements were significantly lower at the end of follow-up (0.55 +/- 0.21 U/kg body weight) in comparison with before use of CSII (0.70 +/- 0.20, P < or = 0.001). BMI increased from 24.0 +/- 3.1 to 24.4 +/- 3.2 kg/m(2) after 24 months (P < or = 0.025). The rate of episodes of diabetic ketoacidosis per year remained unchanged. Mild and severe hypoglycaemic episodes were significantly reduced. The scores in all subsets of the Diabetes Quality-of-Life (DQoL) questionnaire significantly improved after 24 months of CSII. CSII, commenced according to the criteria for a nationally funded clinical programme, improves glycaemic control and quality-of-life outcomes with fewer hypoglycaemic episodes in T1D subjects previously conventionally treated with MDI.

Efficacy and Safety of Mitiglinide in Korean Type 2 Diabetic Patients: Prospective Randomised Multicenter Comparative Phase III Study

Background: Mitiglinide, one of the meglitinides, is expected to prevent postprandial hyperglycemia of type 2 diabetes by enhancing early phase insulin secretion. The aim of this study was to verify the efficacy and safety of mitiglinide compared to nateglinide. Methods: One hundred eleven of diabetic patients were randomised and administered of mitiglinide (n = 56) and nateglinide (n = 55) before a meal time for 12 weeks. The changes of HbA1c, fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) were analyzed. The safety of this drug was investigated as well. Results: The change of HbA1c was not significantly different between two groups (-0.77 ± 1.08% in mitiglinide vs. -0.66 ± 0.79% in nateglinide, P = 0.57). The reduction of FPG (-12.2 ± 25.0 mg/dL vs. -6.1 ± 22.3 mg/dL, P = 0.218), PPG 1 hr (-48.0 ± 47.1 mg/dL, vs. -29.4 ± 43.2 mg/dL, P = 0.051), and PPG 2 hr (-59.2 ± 58.0 mg/dL vs. -43.3 ± 59.0 mg/dL, P = 0.194) were not significantly different between the mitiglinide and the nateglinide, respectively. Drug-related adverse effects were not different between two groups (16.1% in mitiglinide vs. 27.8% in nateglinide, P = 0.137). The frequency of hypoglycemic events were not different between two groups (8.9% in mitiglinide vs. 14.8% in nateglinide, P = 0.339). There were two patients who had complained shoulder pain in the mitiglinide or deterioration of visual acuity in the nateglinide, but those were found to be unrelated with medications. Conclusion: This study showed that mitiglinide had reduced HbA1c as similar to nateglinide and that significantly improved HbA1c, FPG and PPG during 12 weeks of treatment. The safety of mitiglinide was also comparable to nateglinide. Mitiglinide could be used as an effective glucose-lowering agent by enhancing early insulin secretion and reducing postprandial glucose excursion, and thereby might contribute long-term cardioprotective effect in Korean type 2 diabetic patients. (J Kor Diabetes Assoc 31:163~174, 2007)

Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and NPH‐based multiple daily insulin injections (MDI) on glycaemic control and quality of life: results of the 5‐nations trial

The goal of the study was to determine whether continuous subcutaneous insulin infusion (CSII) differs from a multiple daily injection (MDI) regimen based on neutral protamine hagedorn (NPH) as basal insulin with respect to glycaemic control and quality of life in people with Type 1 diabetes. The 5-Nations trial was a randomized, controlled, crossover trial conducted in 11 European centres. Two hundred and seventy-two patients were treated with CSII or MDI during a 2-month run-in period followed by a 6-month treatment period, respectively. The quality of glycaemic control was assessed by HbA(1c), blood glucose values, and the frequency of hypoglycaemic events. For the evaluation of the quality of life, three different self-report questionnaires have been assessed. CSII treatment resulted in lower HbA(1c) (7.45 vs. 7.67%, P < 0.001), mean blood glucose level (8.6 vs. 9.4 mmol/l, P < 0.001) and less fluctuation in blood glucose levels than MDI (+/- 3.9 vs. +/- 4.3 mmol/l, P < 0.001). There was a marked reduction in the frequency of hypoglycaemic events using CSII compared with MDI, with an incidence ratio of 1.12 [95% confidence interval (CI): 1.08-1.17] and 2.61 (95% CI: 1.59-4.29) for mild and severe hypoglycaemia, respectively. The overall score of the diabetes quality of life questionnaire was higher for CSII (P < 0.001), and an improvement in pump users' perception of mental health was detected when using the SF-12 questionnaire (P < 0.05). CSII usage offers significant benefits over NPH-based MDI for individuals with Type 1 diabetes, with improvement in all significant metabolic parameters as well as in patients' quality of life. Additional studies are needed to compare CSII with glargine- and detemir-based MDI.

Continuous Subcutaneous Insulin Infusion and Multiple Dose of Insulin Regimen Display Similar Patterns of Blood Glucose Excursions in Pediatric Type 1 Diabetes

Continuous subcutaneous insulin infusion (CSII) is believed to decrease glycemic variability and clinical hypoglycemia compared with the multiple daily insulin (MDI) regimen. To compare the indices of glycemic instability between CSII and MDI, we analyzed the continuous glucose monitoring system (CGMS) (Medtronic MiniMed, Northridge, CA) profiles of a group of children with type 1 diabetes mellitus with history of frequent blood glucose (BG) fluctuations and hypoglycemia. Data from 14 (nine girls, five boys) patients (3.9-16.8 years old) on CSII and 14 age- and sex-matched (nine girls, five boys) patients (3.9-16.0 years old) on MDI with similar glycemic control (hemoglobin A1c: 7.9 +/- 1.0% vs. 7.9 +/- 1.5%) and body mass index (BMI) (20.1 +/- 4.3 vs. 19.9 +/- 4.1 kg/m(2)) were evaluated by the CGMS. Mean BG (MBG), absolute means of daily differences (MODD), mean amplitude of glycemic excursion (MAGE), and number of hypoglycemic events (BG <60 mg/dL) for 48 h were calculated. The MBG, MODD, MAGE, and number and mean duration of hypoglycemia events in the CSII group were similar to those in the MDI group. The MAGE had an inverse correlation with age (CSII: r (2) = 0.52, P = 0.003; MDI: r (2) = 0.29, P < 0.04) and BMI (CSII: r (2) = 0.38, P < 0.02; MDI: r (2) = 0.71, P < 0.0002). However, there was a positive relationship between MAGE and bolus:basal insulin ratio in the CSII (r (2) = 0.28, P < 0.05) and MDI (r (2) = 0.33, P < 0.03) groups. Also, the MAGE had a positive correlation with frequency of hypoglycemic events in the CSII (r (2) = 0.44, P < 0.01) and MDI (r (2) = 0.35, P < 0.03) groups. The CSII and MDI regimens in children and adolescents with comparable glycemic control displayed similar patterns of glycemic excursions, implying that factors influencing glycemic instability in pediatric type 1 diabetes mellitus appear to be independent of treatment modality.

A quality-of-life assessment of intensive insulin therapy using insulin lispro switched from short-acting insulin and measured by an ITR-QOL questionnaire: a prospective comparison of multiple daily insulin injections and continuous subcutaneous insulin infusion

We examined quality-of-life (QOL) of patients with a prospective comparison of multiple daily insulin injections therapy (16 patients in MDI group) and continuous subcutaneous insulin infusion therapy (12 patients in CSII group) using insulin lispro (LP), which was switched from short-acting insulin on the basis of a questionnaire about insulin-therapy-related QOL measure (ITR-QOL). The overall score of ITR-QOL before using LP in the CSII group was significantly higher ( P<0.01) than the MDI group. In four subscales of ITR-QOL, the scores of social and daily activities and of therapy-related feelings in the CSII group were significantly higher ( P<0.02) than those in the MDI group, respectively, while there was no significant difference in the score of physical function between the two groups. Three months after using LP, the score of daily activities in the MDI group was significantly higher ( P<0.02) than that before using LP, while there were no significant differences in other scores of the two groups. There were no significant differences in HbA1c between two groups before and after using LP. The frequency of hypoglycemic events in the MDI group before using LP was higher than that in the CSII group and decreased after using LP. These results show that QOL of patients treated by CSII is superior to that treated by MDI and demonstrate that insulin lispro has a more beneficial effect on daily activities in patients treated by MDI than short-acting insulin.

A retrospective cohort analysis of the clinical effectiveness of a physician-pharmacist collaborative drug therapy management diabetes clinic.

The glycemic control of patients with diabetes in a physician-supervised, pharmacist-managed primary care clinic was compared with that of patients receiving standard care in the same health care system. We retrospectively analyzed the glycemic control of 87 men with type 1 or type 2 diabetes whose diabetes-related drug therapy was managed by clinical pharmacists compared with a control group of 85 similar patients whose care was not augmented by clinical pharmacists. Primary outcomes were differences in fasting blood glucose (FBG) and glycosylated hemoglobin (A1C) levels between groups. Secondary outcomes were relative risk (RR) for achieving an A1C of 7% or below, frequency of diabetes-related scheduled and unscheduled clinic visits, and frequency of hypoglycemic events. The study group had 864 clinic visits and the control group had 712 between October 1997 and June 2000. No statistical differences were noted in FBG or A1C between groups. The RR of achieving an A1C of 7% or below was significantly higher in the study cohort (RR 5.19, 95% confidence interval [CI] 2.62-10.26). The frequency of hypoglycemic events did not differ between groups. The mean +/- SD frequency of unscheduled diabetes-related clinic visits/patient/year was higher in the control group (1.33 +/- 3.74) than in the study group (0.11 +/- 0.46, p = 0.003). Pharmacist-managed diabetes care was effective in improving glycemic control and was not associated with an increased risk for hypoglycemic events or unscheduled diabetes-related clinic visits.

Efficacy of insulin lispro in combination with NPH human insulin twice per day in patients with insulin-dependent or non—insulin-dependent diabetes mellitus

A common treatment regimen for patients with either insulin-dependent diabetes mellitus (IDDM) or non—insulin-dependent diabetes mellitus (NIDDM) is a combination of rapid-acting insulin and intermediate-acting insulin administered twice each day. It is usually recommended that regular human insulin be injected 30 to 45 minutes before a meal. In practice, patients often inject regular human insulin closer to mealtime, causing a higher postprandial serum glucose level and an increased potential for hypoglycemia in the postabsorptive period. Insulin lispro, a rapid-acting insulin analogue, is best injected just before a meal because of its more rapid absorption and shorter duration of action. In 707 randomized patients, 379 with IDDM and 328 with NIDDM, we studied the effect of twice-daily insulin lispro or regular human insulin in combination with NPH human insulin (isophane insulin) on premeal, 2-hour postprandial, and bedtime glycemic control. Assessments were based on the results of a seven-point blood glucose profile, the insulin dose (by formulation and time of administration), the incidence and frequency of hypoglycemic episodes, and the glycated hemoglobin value. Treatment with insulin lispro resulted in lower postprandial glucose levels and smaller increases in glucose level after the morning and evening meals compared with treatment with regular human insulin. Overall glycemic control, frequency of hypoglycemic events, and total insulin dose were not different between the two groups. Insulin lispro in combination with NPH human insulin in a twice-per-day regimen allows injection closer to mealtime and improves postprandial glycemic control without increasing the risk of hypoglycemia.

Glibenclamide vs Gliclazide in Type 2 Diabetes of the Elderly

The objective of this study was to compare the effect of two sulphonylureas on the frequency of hypoglycaemic events and glycaemic control in elderly patients with Type 2 diabetes. Twenty-two untreated elderly patients were treated with glibenclamide or gliclazide in a randomized double-blind fashion. Prior to treatment, a biochemical profile, an oral glucose tolerance test, and a 2-h hyperglycaemic glucose clamp (glucose 5.4 mmol l-zs-1 above baseline) were performed. Patients were seen regularly over 6 months to assess glycaemic control and the frequency of hypoglycaemic reactions. Hyperglycaemic clamp studies and oral glucose tolerance tests were repeated at 1 and 6 months. The area under the curve for the oral glucose tolerance test (glibenclamide: 15.5 +/- 0.7; gliclazide: 14.9 +/- 0.8 mmol l-1 (p = NS)) and the haemoglobin A1C (glibenclamide: 7.4 +/- 0.2%; gliclazide: 7.9 +/- 0.5% (p = NS)) were similar at 6 months. Hypoglycaemic reactions were significantly more frequent with glibenclamide than with gliclazide: 17 vs 4 (p < 0.01). Insulin sensitivity index (ml kg-1 min-1 pmol-1 x 100) was increased significantly by glibenclamide but not gliclazide (glibenclamide: 0.284 +/- 0.116 (baseline) vs 0.518 +/- 0.102 (6 months) (p < 0.05), gliclazide: 0.260 +/- 0.048 (baseline) vs 0.358 +/- 0.048 (6 months) (p = NS)). We conclude that glycaemic control was equivalent with the two drugs but the incidence of hypoglycaemic reactions was significantly greater with glibenclamide probably because this drug increases insulin sensitivity to a greater degree.