Low Rate Of Hypoglycaemia Research Articles

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Bangalore cohort of the A 1 chieve study

Background:The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents.Materials and Methods:Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Bangalore, India.Results:A total of 1533 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 1262), insulin detemir (n = 165), insulin aspart (n = 86), basal insulin plus insulin aspart (n = 11) and other insulin combinations (n = 2). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 9.2%) and insulin users (mean HbA1c: 8.8%) groups. After 24 weeks of treatment, both groups showed improvement in HbA1c (insulin naïve: −1.3%, insulin users: −1.5%). SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients.Conclusion:Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Rajasthan cohort of the A 1 chieve study

Background:The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents.Materials and Methods:Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Rajasthan, India.Results:A total of 477 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 340), insulin detemir (n = 90), insulin aspart (n = 37), basal insulin plus insulin aspart (n = 7) and other insulin combinations (n = 2). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 8.3%) and insulin user (mean HbA1c: 8.4%) groups. After 24 weeks of treatment, both the groups showed improvement in HbA1c (insulin naïve: −0.9%, insulin users: −1.2%). Major hypoglycaemic events decreased from 0.5 events/patient-year to 0.0 events/patient-year in insulin naïve group while no change from baseline (1.3 events/patients-year) was observed for insulin users. SADRs were not reported in any of the study patients.Conclusion:Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Safety and efficacy of sitagliptin-metformin in fixed combination for the treatment of type 2 diabetes mellitus.

The biguanide, metformin, is considered first-line treatment for type 2 diabetes. Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor acts through the incretin pathway and has a glucose dependent mode of action. The complementary hypoglycemic properties of these drugs make fixed dose combination treatment an attractive prospect. Evidence from recent clinical trials suggests a beneficial effect of the combination on efficacy, demonstrated by significant improvement of hemoglobin A1c (HbA1c), fasting and postprandial glucose levels. The fixed dose combination is likely to have greater patient tolerability compared with monotherapy with either agent because of low rates of hypoglycemia, weight neutrality, and lower rates of side effects. High acquisition cost and paucity of long-term safety data are, however, potential barriers to their wider use. An overview of the pharmacology and clinical outcomes from recent trials of the metformin-sitagliptin combination and how the combination could fit into the type 2 diabetes treatment algorithm is presented in this review.

Glucose Control During Labour In Diabetic Women

ObjectiveGlucose control during labour is important for mother and neonate, with high rates of neonatal hypoglycemia reported in offspring of women with pre-existing or gestational diabetes (48% and 19%, respectively). How glucose control can be achieved is rarely specified. We conducted a chart review of a standardized approach using an iterative intravenous insulin-glucose infusion. MethodsWe performed a retrospective review of the records of 274 diabetic women during labour. Fifty-five women had type 1 diabetes, 55 had type 2 diabetes, and 164 had gestational diabetes (GDM). The protocol used hourly capillary blood glucose determinations, each prompting changes in insulinglucose infusion rates as required. Outcomes included maternal blood glucose levels three hours before delivery and neonatal hypoglycemia (blood glucose < 2 mmol/L). ResultsThe insulin-glucose infusion was used in 47% of women with type 1, type 2, and gestational diabetes requiring ≥ 0.5 units/kg/day of insulin during pregnancy and in 8% of women with GDM treated by diet or < 0.5 units/kg/day of insulin. The overall rate of maternal hypoglycemia was low (6.6% with blood glucose ≤ 3.5 mmol/L and 1.5% ≤ 3.0 mmol/L) pre-delivery; 13.9% of women had a blood glucose level ≥ 7.0 mmol/L. The neonatal hypoglycemia rate was 7.3% (4.9% in the offspring of women with GDM and 10.9% in the offspring of women with pre-existing diabetes). In women with type 1 and type 2 diabetes and high-dose insulin-requiring GDM, the rate of blood glucose values outside the range of 3.6 to 6.9 mmol/L was lower in those using the intravenous protocol (16.7%) than in those not using it (34.8%), but this reduction was not statistically significant. ConclusionStandardized management for diabetic women in labour using an intravenous insulin-glucose protocol was effective in achieving stable maternal blood glucose levels with low rates of neonatal hypoglycemia.

Long‐term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2‐year results from the LEAD‐2 study

To investigate efficacy and safety of dual therapy with liraglutide and metformin in comparison to glimepiride and metformin, and metformin monotherapy over 2 years in patients with type 2 diabetes. In the 26-week the Liraglutide Effect and Action in Diabetes (LEAD)-2 core trial, patients (n = 1091) were randomized (2 : 2 : 2 : 1: 2) to liraglutide (0.6, 1.2 or 1.8 mg once-daily), placebo or glimepiride; all with metformin. Patients were enrolled if they were 18-80 years old with HbA1c 7.0-11.0% (previous monotherapy ≥3 months), or 7.0-10.0% (previous combination therapy ≥3 months), and body mass index ≤40 kg/m(2) . Patients completing the 26-week double-blinded phase could enter an 18-month open-label extension. HbA1c decreased significantly with liraglutide (0.4% with 0.6 mg, 0.6% with 1.2 and 1.8 mg) versus 0.3% increase with metformin monotherapy (p < 0.0001). HbA1c decrease with liraglutide was non-inferior versus 0.5% decrease with glimepiride. Liraglutide groups experienced significant weight loss (2.1, 3.0 and 2.9 kg with 0.6, 1.2 and 1.8 mg, respectively) compared to weight gain (0.7 kg) with glimepiride (p < 0.0001). Weight loss with liraglutide 1.2 and 1.8 mg was significantly greater than with metformin monotherapy (1.8 kg; p = 0.0185 and p = 0.0378 for 1.2 and 1.8 mg, respectively). The occurrence of minor hypoglycaemia was <5.0% in all liraglutide groups, significantly less than with glimepiride (24.0%; p < 0.0001). Liraglutide was well tolerated overall: gastrointestinal events were more common than with glimepiride or metformin monotherapy, but occurrence decreased with time. Liraglutide provided sustained glycaemic control over 2 years comparable to that provided by glimepiride. Liraglutide was well tolerated, and was associated with weight loss and a low rate of hypoglycaemia.

Less Nocturnal Hypoglycemia for Insulin Degludec vs. Insulin Glargine in Subjects with T1DM and Baseline A1c of 7.5–8.5%: A Meta-Analysis

The risk of hypoglycemia increases as A1c levels approach recommended targets. Insulin degludec (IDeg) is a new basal insulin that forms soluble multi-hexamers upon injection, resulting in an ultra-long action profile. We analyzed whether IDeg allows improved glycemic control together with lower rates of hypoglycemia vs. insulin glargine (IGlar) in T1DM patients with baseline A1c 7.5–8.5%. Changes in A1c and fasting plasma glucose (FPG) and rates of hypoglycemia were analyzed with linear models. Hypoglycemia was defined as rates of self-reported confirmed hypoglycemia (PG<[3.1 mmol/L] 56 mg/dL or severe episodes requiring assistance) and nocturnal confirmed hypoglycemia (onset 00:01–05:59h, inclusive). The analysis included all open-labeled randomized treat-to-target phase 3a trials in T1DM, where IDeg (n=223) and IGlar (n=109) were dosed once daily in a basal–bolus regimen. A1c decreased from 8.0% at baseline in both groups to 7.6 vs. 7.5% for IDeg vs. IGlar, respectively (treatment difference: 0.05 [–0.12;0.22] 95% CI). FPG decreased from 9.7 to 7.9 mmol/L for IDeg vs. 9.8 to 9.1 mmol/L for IGlar (treatment difference: –1.01 mmol/L [–1.95;–0.08] 95% CI). There was no difference in overall hypoglycemia or severe hypoglycemia. Despite the lower FPG achieved with IDeg, the rate of nocturnal hypoglycemia was lower with IDeg compared to IGlar (rate ratio: 0.68 [0.50;0.93] 95% CI). In conclusion, for patients with T1DM and baseline A1c of 7.5–8.5%, treatment with IDeg results in comparable improvement in A1c with significantly lower rate of nocturnal hypoglycemia (32%) and greater reduction in FPG compared to IGlar.

The safety and efficacy of adding once‐daily insulin detemir to oral hypoglycaemic agents in patients with type 2 diabetes in a clinical practice setting in 10 countries

Evaluate the safety and efficacy of once-daily insulin detemir initiated in routine clinical practice in patients with type 2 diabetes mellitus inadequately controlled with oral hypoglycaemic agents (OHAs). This large observational study was conducted in 10 countries. Adverse event data (including hypoglycaemia) and glycaemic control were recorded before and 24 weeks following insulin initiation while patients continued routine clinical management. In this study, 17 374 patients (53% male) were included. Mean pre-insulin values (±s.d.) were: age 62 ± 12 years; body mass index (BMI) 29.3 ± 5.4 kg/m(2); diabetes duration 10 ± 7 years; haemoglobin A1c (HbA1c) 8.9 ± 1.6%. During the study, 27 patients experienced serious adverse drug reaction, severe hypoglycaemic events or both; and there were 31 episodes of severe hypoglycaemia in 21 patients. After 24 weeks, HbA1c was 7.5 ± 1.2% (change of -1.3%; p < 0.001) and mean weight change was -0.6 kg (confidence interval -0.7, -0.5 kg, p < 0.001). Daily insulin dose increased from 13 ± 6 U (0.16 ± 0.09 U/kg) to 22 ± 16 U (0.27 ± 0.17U/kg) by 24 weeks. Multivariate regression analysis identified several independent demographic and treatment predictors of end of study HbA1c. Addition of once-daily insulin detemir to patients with type 2 diabetes mellitus on OHA therapy resulted in few adverse events, significant improvements in glycaemic control, small reductions in weight and low rates of hypoglycaemia. On the basis of this study, concerns about hypoglycaemia or weight gain should not preclude initiation of basal insulin analogues in patients with poor glycaemic control on OHAs.

Efficacy and safety of biphasic insulin aspart 70/30 in type 2 diabetes patients of different race or ethnicity (INITIATEplus trial)

Objective:To determine if self-titration using biphasic insulin aspart 70/30 (BIAsp 30) had a different impact on efficacy and safety across different racial/ethnic subgroups.Research design/methods:This was an exploratory, post hoc analysis by race (White vs. Black/African-American) and ethnicity (Hispanic/Latino vs. non-Hispanic/Latino) of data from the INITIATEplus trial. Participants were treated twice-daily with BIAsp 30 over 24 weeks.Trial registration:ClinicalTrials.gov identifier: NCT00101751.Main outcome measures:Efficacy endpoints included reductions in mean glycated hemoglobin (A1C) and fasting plasma glucose (FPG). Safety endpoints included hypoglycemia rates (events/patient-year) and adverse events. Body weight changes were also measured.Results:Glycemic control improved by a similar extent for all demographic groups. Observed mean decreases in A1C ranged from 2.4% to 2.6% after 24 weeks’ treatment. Baseline-adjusted mean A1C decreases for White vs. Black/African-American subjects were 2.56% and 2.13% (p < 0.0001), and for Hispanic/Latino vs. non-Hispanic/Latino subjects were 2.45% and 2.42% (p = 0.677), respectively. Final FPG values were similar among all groups (141–146 mg/dL [7.83–8.10 m mol/L]), and baseline-adjusted FPG decreases were not significantly different (p > 0.025) between groups. Hypoglycemia was low for White, Black/African-American, Hispanic/Latino, and non-Hispanic/Latino subjects (0.08, 0.04, 0.03, and 0.07 major events/patient-year, with 0.60, 0.30, 0.37, and 0.52 minor events/patient-year, respectively). Body weight increases were 3.17 and 3.06 kg (White vs. African-American) and 2.69 and 3.19 kg (Hispanic/Latino vs. non-Hispanic/Latino). Final weight-adjusted total daily insulin doses were 0.60 U/kg for Black/African-American subjects vs. 0.78 U/kg for White subjects (p < 0.0001), and 0.71 U/kg for Hispanic/Latino subjects vs. 0.74 U/kg for non-Hispanic/Latino subjects (p = 0.42).Limitations:The trial was not designed or powered for comparisons across racial or ethnic groups, subjects were not stratified for pre-baseline medication regimens between each race and ethnic group, and unequal subject numbers and baseline A1C disparities existed between the pairs of groups being compared.Conclusions:Diabetes self-management with BIAsp 30 using an easily followed self-titration algorithm produced low hypoglycemia rates. All subgroups achieved A1C reductions >2.1% and FPG declines >82 mg/dL that were similar across groups, demonstrating that self-titration of BIAsp 30 can successfully be pursued in a primary care setting by patients who had previously failed to meet ADA A1C targets under oral antidiabetes therapy, with race or ethnicity not an obstacle to achieving better glycemic control.

Sequential Intensification of Metformin Treatment in Type 2 Diabetes With Liraglutide Followed by Randomized Addition of Basal Insulin Prompted by A1C Targets

OBJECTIVEWe evaluated the addition of liraglutide to metformin in type 2 diabetes followed by intensification with basal insulin (detemir) if glycated hemoglobin (A1C) ≥7%.RESEARCH DESIGN AND METHODSIn 988 participants from North America and Europe uncontrolled on metformin ± sulfonylurea, sulfonylurea was discontinued and liraglutide 1.8 mg/day added for 12 weeks (run-in). Subsequently, those with A1C ≥7% were randomized 1:1 to 26 weeks’ open-label addition of insulin detemir to metformin + liraglutide (n = 162) or continuation without insulin detemir (n = 161). Patients achieving A1C <7% continued unchanged treatment (observational arm). The primary end point was A1C change between randomized groups.RESULTSOf 821 participants completing the run-in, 61% (n = 498) achieved A1C <7% (mean change −1.3% from 7.7% at start), whereas 39% (n = 323) did not (−0.6% from 8.3% at start). During run-in, 167 of 988 (17%) withdrew; 46% of these due to gastrointestinal adverse events. At week 26, A1C decreased further, by 0.5% (from 7.6% at randomization) with insulin detemir (n = 162) versus 0.02% increase without insulin detemir (n = 157) to 7.1 and 7.5%, respectively (estimated treatment difference −0.52 [95% CI −0.68 to −0.36]; P < 0.0001). Forty-three percent of participants with insulin detemir versus 17% without reached A1C <7%. Mean weight decreased by 3.5 kg during run-in, then by 0.16 kg with insulin detemir or 0.95 kg without insulin detemir. In the randomized phase, no major hypoglycemia occurred and minor hypoglycemia rates were 0.286 and 0.029 events per participant-year with and without insulin detemir (9.2 vs. 1.3%).CONCLUSIONSSupplementation of metformin with liraglutide and then insulin detemir was well tolerated in the majority of patients, with good glycemic control, sustained weight loss, and very low hypoglycemia rates.

Pharmacist Glycemic Control Team Improves Quality of Glycemic Control in Surgical Patients with Perioperative Dysglycemia

Perioperative hyperglycemia is a risk factor for increased morbidity and mortality. Improved glycemic control has been demonstrated to reduce surgical site infections, reduce perioperative morbidity, and reduce length of stay. However, safe and effective perioperative glycemic control can be limited by expert clinician availability. To improve quality by reliably providing safe and effective glycemic control to surgical patients with diabetes or stress hyperglycemia. A designated group of pharmacists, the Glycemic Control Team (GCT), worked under protocol, on a consultation basis, to manage perioperative dysglycemia during hospitalization. We used a pre-post, observational study design to assess the effectiveness of the intervention and implementation of the GCT. The proportion of patients pre- and postintervention with good glycemic control and with hypoglycemia were measured and compared. We defined good glycemic control as having all, or all but one, point-of-care blood glucose values between 70-180 mg/dL in each 24-hour period. We defined hypoglycemia as having any point-of-care test glucose value <70 mg/dL in any of the 3 days evaluated. During the preimplementation period, 77.4% of postoperative patient days demonstrated good glycemic control. In the postimplementation period, this percentage increased to 90.3%. Over the same period, the rate of hypoglycemia decreased from 8.6% to 4.6%. Implementation of a pharmacist team to manage glycemic control in hospitalized, postoperative patients led to safer and better quality of glycemic care as measured by improved glycemic control and lower rates of hypoglycemia.

Treatment of Diabetic Ketoacidosis (DKA) with 2 Different Regimens Regarding Fluid Substitution and Insulin Dosage (0.025 vs. 0.1 units/kg/h)

Diabetic ketoacidosis (DKA) is still the most dangerous acute complication in type 1 diabetes. The aim of this study was to compare treatment of DKA with a regimen of a low insulin dose (0.025 units/kg/h) vs. a standard insulin dose (0.1 units/kg/h).We retrospectively analysed all cases of children and adolescents (age 0-18 years) with type 1 diabetes and DKA who needed treatment in the ICU in the time period of 1998-2005 in 2 pediatric diabetes centers. In a chart review of the first 48 h after onset of DKA the following parameters where evaluated: pH, blood glucose, sodium, potassium, and ketones in urine. Consciousness, neurological status and complications such as cerebral edema, hypoglycaemia or hypokalemia were also recorded.23 children were treated in center A (low insulin dose) whereas 41 where treated in center B (standard insulin dose). Mean age of the patients was 8.9 (range 1.58-17.7) and 13.5 years (1.25-17.7) respectively (p=0.134). Mean pH was 7.1 and HCO3 was 9.05 and 7.79 respectively (p=0.122). Initial blood glucose was 26 mmol/l (no difference between the 2 centres). Treatment with the standard insulin dose resulted in a slightly shorter duration of acidosis (8 h in center A, 6.5 h in center B) and a significantly faster normalization of blood glucose (18 h in A, vs. 10.5 h in B) (p<0.005). During the first day we found similar and very low rates of hypoglycaemia. In center B one case of suspected cerebral edema and cerebral infarction occurred.Low dose insulin substitution is as safe as the recommended standard dose in respect to the occurrence of acute complications. Acidosis is broken slightly earlier with the standard dose. Implications of this earlier normalisation of pH remain unclear.

Critical Illness Hyperglycemia in Pediatric Cardiac Surgery

Critical illness hyperglycemia (CIH) is common in pediatric and adult intensive care units (ICUs). Children undergoing surgical repair or palliation of congenital cardiac defects are particularly at risk for CIH and its occurrence has been associated with increased morbidity and mortality in this population. Strict glycemic control through the use of intensive insulin therapy (IIT) has been shown to improve outcomes in some adult and pediatric studies, yet these findings have sparked controversy. The practice of strict glycemic control has been slow in extending to pediatric ICUs because of the documented increase in the incidence of hypoglycemia in patients treated with IIT. Protocol driven approaches with more liberal glycemic targets have been successfully validated in general and cardiac critical care pediatric patients with low rates of hypoglycemia. It is unknown whether a therapeutic benefit is obtained by keeping patients in this more liberal glycemic control target. Definitive randomized controlled trials of IIT utilizing these targets in critically ill children are ongoing.

Strategies for insulin initiation: insights from the French LIGHT observational study

The progressive nature of type 2 diabetes necessitates exogenous insulin use for most patients; basal insulin plus oral anti-diabetes drugs (OADs) is a well-validated way to facilitate insulin initiation. The primary aim of this study was to explore insulin initiation strategies and outcomes for patients using insulin detemir or glargine plus oral anti-diabetes drugs. LIGHT was a 3-month, longitudinal observational study conducted across 761 French centres in insulin-naïve type 2 diabetes patients managed under routine clinical care conditions, in either primary or secondary care. Endpoints included changes in HbA(1c) , fasting plasma glucose (FPG), rate of hypoglycaemia, weight, and adverse events. Most physicians initiated a basal analogue to improve glycaemic control (97%), with many delaying beginning treatment for several months (9 ± 9.0 months for general practitioners, 10.2 ± 16.2 months for specialists). Most patients continued oral anti-diabetes drug therapy (95%) and lifestyle measures (92%), with 2-3 blood glucose readings per day and follow-up telephone calls for dose optimization. Mean change in HbA(1c) from baseline was - 1.3%, and - 3.1 mmol/L for fasting plasma glucose (both p < 0.0001). Hypoglycaemia increased from 1.4 to 5.6 events/patient/year (p < 0.0001), and weight decreased on average by 0.5 kg with detemir, with no change in glargine. Most patients (93%) reported being satisfied or very satisfied with their insulin. Insulin initiation with detemir or glargine can be successfully managed in both primary and secondary care; the benefits of basal analogues (once-daily dosing, low rates of hypoglycaemia compared with neutral protamine Hagedorn) may have contributed to patient acceptance of the regimen.

The role of GLP-1 mimetics and basal insulin analogues in type 2 diabetes mellitus: guidance from studies of liraglutide.

In people with type 2 diabetes mellitus (T2DM), the incretin effect is reduced, but the recent advent of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide (GLP)-1 agonists/analogues has enabled restoration of at least some of the function of the incretin system, with accompanying improvements in glycaemic control. Two GLP-1 receptor agonists/analogues are currently approved for the treatment of T2DM—exenatide (Byetta®, Eli Lilly & Co., Indianapolis, IN, US) and liraglutide (Victoza®, Novo Nordisk, Bagsvaerd, Denmark); a once-weekly formulation of exenatide (Bydureon®, Eli Lilly & Co.) has also been approved by the European Medicines Agency. The National Institute for Health and Clinical Excellence (NICE) has recently published guidance on the use of liraglutide in T2DM, based on evidence from the Liraglutide Effect and Action in Diabetes (LEAD) Phase III trial programme, which compared liraglutide with existing glucose-lowering therapies, such as exenatide and insulin glargine. The LEAD programme reported HbA1c reductions from 0.8 to 1.5% with liraglutide (1.2 and 1.8 mg), accompanied by low rates of hypoglycaemia and some weight loss; side effects were primarily gastrointestinal in nature (e.g. nausea and diarrhoea). Based on the findings of the LEAD studies and the NICE recommendation, liraglutide now represents an important therapy widely available in the UK for certain patient groups, including those with a body mass index (BMI) ≥35.0 kg/m2, and patients with a BMI <35 kg/m2 who are considered unsuitable for insulin and are failing to meet targets for glycaemic control with oral agents. NICE guidelines still suggest that most patients without considerable obesity (BMI <35 kg/m2) are probably best managed using insulin therapy. Evidence also suggests a future role for GLP-1 mimetics in combination with basal insulin.

Willingness-to-pay for benefits associated with basal insulin treatment of type 2 diabetes

Data from a 20-week trial comparing insulin detemir and neutral protamine Hagedorn (NPH) insulin in insulin-naïve people with type 2 diabetes were analyzed using willingness-to-pay (WTP) data, a proxy for patient preference. The advantages of insulin detemir relative to NPH insulin with respect to a lower hypoglycemia rate and less weight gain were associated with a value of €27.87 per month.

Triple Therapy with Liraglutide + Metformin + Insulin Detemir Improves Glycemic Control with No Weight Gain and Low Rates of Hypoglycemia

Triple Therapy with Liraglutide + Metformin + Insulin Detemir Improves Glycemic Control with No Weight Gain and Low Rates of Hypoglycemia

Next-Generation GLP-1 Therapy: An Introduction to Liraglutide

Liraglutide, a once-daily human glucagon-like peptide-1 (GLP-1) analog, was approved by the US Food and Drug Administration in 2010 for the treatment of type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 enhances insulin secretion and inhibits glucagon in a glucose-dependent manner. The efficacy and safety of liraglutide were evaluated in 6 phase 3 trials in > 4000 patients in the Liraglutide Effect and Action in Diabetes (LEAD) program, in another trial in comparison with sitagliptin, and in another trial where basal insulin was added to liraglutide + metformin. At liraglutide doses of 1.2 mg or 1.8 mg once daily, significant mean reductions in glycated hemoglobin (HbA1) (1%-1.6%) and fasting plasma glucose (15–43 mg/dL), as well as sustained weight loss (2-3 kg) and a low rate of hypoglycemia occurred. Mild and transient nausea, reported in 6% to 41% of patients, was the most frequent adverse event reported. Incretin-based therapies such as liraglutide provide an important expansion of options for the treatment of T2DM. Keywords: type 2 diabetes mellitus; liraglutide; GLP-1; drug therapy

An Insulin Protocol for Management of Hyperglycemia in Patients Receiving Parenteral Nutrition Is Superior to Ad Hoc Management

The authors investigated whether an insulin protocol for parenteral nutrition (PN)-induced hyperglycemia is superior to conventional management relying primarily on sliding-scale insulin at a large county hospital. A prospective cohort study with historical controls was completed. Adult patients receiving PN were managed with a protocol that determined insulin doses based on carbohydrate delivery and capillary blood glucose (CBG) if half or more of CBG measurements in the first 24 hours after initiation of PN exceeded 140 mg/dL. Control data were obtained from records of patients who met study eligibility criteria but had been managed before implementation of the insulin protocol. Mean CBG after the start of insulin therapy was 138 ± 37 mg/dL for protocol patients and 159 ± 46 mg/dL for controls (P < .0001). Proportion of CBG values in the target range of 80-140 mg/dL was 60% in the protocol group and 35% in the control group (P < .0001). Hypoglycemia, defined as CBG <80 mg/dL, occurred infrequently but more often in the protocol group (3% vs 1%, P = .012). There was no difference in total daily insulin between groups, although protocol patients received mostly scheduled insulin (93% total daily dose), whereas control patients received predominantly supplemental insulin (66% total daily dose). Protocol-directed management of PN-induced hyperglycemia is superior to ad hoc insulin dosing. Linking insulin to carbohydrate in PN leads to improved glycemic control with a low rate of hypoglycemia.

Extremelt low rates of hypoglycemia following transfer of tight glucose control management to ICU nurses

Tight glucose control (TGC) failed to improve survival and has been associated with high rates (6-18%) of hypoglycemia (< 2.5mmol/l), themselves associated with significant mortality. Blood glucose levels vary largely in critically ills and TCG requires individualized knowledge of the patient condition. Bedside frequent blood glucose measurements are mandatory for continue adaptations of insulin and glucose administration. We progressively transfer TGC to the nursing personal.

Two-year glycaemic control and healthcare expenditures following initiation of insulin glargine versus neutral protamine Hagedorn insulin in type 2 diabetes

To compare 2-year glycaemic control, hypoglycaemia and healthcare expenditures following insulin glargine (glargine, n = 2105) or neutral protamine Hagedorn (NPH) insulin (NPH, n = 734) initiation in patients with type 2 diabetes (T2D). Retrospective cohort study using an integrated US health insurance administrative database was conducted. Individuals with a diabetes diagnostic claim and initiated basal insulin therapy with glargine or NPH from 2001 to 2005 dispensed at least one oral antidiabetic drug prescription during 6 months prior to basal insulin initiation and enrolled in the same health insurance plan from 6 months before to 12 months or more after insulin initiation were identified. Repeated measures mixed-effects models evaluated glycaemic and financial outcomes to account for factors potentially contributing to selection of insulin therapy, that is, age, gender, baseline HbA1c level, health expenditures, co-morbidities, healthcare utilization, pharmacy co-payment and follow-up antidiabetic medications. Adjusted mean HbA1c value in the first year following insulin initiation was significantly lower for glargine versus NPH initiators (Δ = -0.43, p = 0.006); this difference diminished in the second year (Δ = -0.16, p = 0.375). First-year adjusted quarterly hypoglycaemia incidence rates were lower for glargine (2.1%) versus NPH (2.4%) (p = 0.02) as was the second-year quarterly rate (1.8 vs. 2.2%; p = 0.01). Both the first- and second-year adjusted total healthcare expenditures were lower in the glargine versus NPH group (year 1: $18,720 vs. $19,996, p = 0.005; year 2: $15,008 vs. $17,336; p < 0.001). Glargine therapy may be an effective long-term option for improving glycaemic control, with lower rates of hypoglycaemia and healthcare costs in patients with T2D.