Mean Change In HbA Research Articles

Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study

Glucagon-like peptide-1 receptor agonists exenatide and liraglutide have been shown to improve glycaemic control and reduce bodyweight in patients with type 2 diabetes. We compared the efficacy and safety of exenatide once weekly with liraglutide once daily in patients with type 2 diabetes. We did a 26 week, open-label, randomised, parallel-group study at 105 sites in 19 countries between Jan 11, 2010, and Jan 17, 2011. Patients aged 18 years or older with type 2 diabetes treated with lifestyle modification and oral antihyperglycaemic drugs were randomly assigned (1:1), via a computer-generated randomisation sequence with a voice response system, to receive injections of once-daily liraglutide (1·8 mg) or once-weekly exenatide (2 mg). Participants and investigators were not masked to treatment assignment. The primary endpoint was change in glycated haemoglobin (HbA(1c)) from baseline to week 26. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01029886. Of 912 randomised patients, 911 were included in the intention-to-treat analysis (450 liraglutide, 461 exenatide). The least-squares mean change in HbA(1c) was greater in patients in the liraglutide group (-1·48%, SE 0·05; n=386) than in those in the exenatide group (-1·28%, 0·05; 390) with the treatment difference (0·21%, 95% CI 0·08-0·33) not meeting predefined non-inferiority criteria (upper limit of CI <0·25%). The most common adverse events were nausea (93 [21%] in the liraglutide group vs 43 [9%] in the exenatide group), diarrhoea (59 [13%] vs 28 [6%]), and vomiting 48 [11%] vs 17 [4%]), which occurred less frequently in the exenatide group and with decreasing incidence over time in both groups. 24 (5%) patients allocated to liraglutide and 12 (3%) allocated to exenatide discontinued participation because of adverse events. Both once daily liraglutide and once weekly exenatide led to improvements in glycaemic control, with greater reductions noted with liraglutide. These findings, plus differences in injection frequency and tolerability, could inform therapeutic decisions for treatment of patients with type 2 diabetes. Eli Lilly and Company and Amylin Pharmaceuticals LLC.

Short-term continuous glucose monitoring: effects on glucose and treatment satisfaction in patients with type 1 diabetes mellitus; a randomized controlled trial

Objective: To assess whether 4 week's use of a continuous glucose monitoring (CGM) system improves glucose control, treatment satisfaction or health status, as compared to intensified conventional finger-prick measurements (ICFM) in patients with type 1 diabetes mellitus (DM1). Method: Thirty patients suffering from DM1 for more than three years and treated with either insulin pumps or multiple daily insulin injections, were included in a randomised controlled cross-over trial. They were Caucasians of both genders, between 18 and 50 years, and had moderately well controlled diabetes. The participants performed either ICFM or CGM for 4 weeks, followed by an 8 week's observation period. Thereafter they were crossed over to the opposite intervention. HbA(1c) , hypoglycaemic episodes, treatment satisfaction and health status were assessed at all meetings, although HbA(1c) was the primary endpoint. Results: At inclusion mean HbA(1c) was 7.8 ± 0.9 %. The mean change in HbA(1c) was -0.2 ± 0.1% and -0.2 ± 0.1% for the CGM and the ICFM periods, accordingly (p = 0.91). The mean changes in HbA(1c) during the combined treatment and observation periods were -0.1 ± 0.1% and -0.2 ± 0.1% for the CGM and the ICFM period, accordingly (p = 0.86). The frequency of severe hypoglycaemic episodes, treatment satisfaction and health status was also equal between the two interventions. No adverse events were observed.

A retrospective database study of insulin initiation in patients with Type 2 diabetes in UK primary care

This study characterized UK primary care patients with Type 2 diabetes who initiated insulin treatment, and described the initial insulin regimens used, overall metabolic changes and health-care resource usage. A retrospective cohort study was performed using quality-checked patient data from The Health Improvement Network database. Eligible patients who initiated insulin for the first time between 2004 and 2006 were grouped into four cohorts according to the type of insulin regimen initiated. Data on patient characteristics, metabolic and clinical outcomes and health-care resource use were collected at baseline and during 6 months of follow-up. In total, 4045 eligible adults [2269 male, 1776 female; mean age 62.6 ± 13.3 years; mean baseline HbA(1c) 82 ± 22 mmol/mol (9.6% ± 2.0%)] initiated insulin. Approximately half (52.4%) initiated insulin as basal insulin only, 41.6% as premixed only, 4.0% as basal-bolus and 2.1% as prandial insulin only. Among patients with ≥ 180 days follow-up (n=3815), the initial insulin regimen was not changed during follow-up in 75.1% of patients, while 13.7% discontinued, 7.0% switched and 4.7% intensified insulin therapy. The mean change in HbA(1c) was -14 mmol/mol (-1.3%, n=2881), with 17.3% of patients achieving an HbA(1c) of <53 mmol/mol (7%, n=3024). The mean weight change was +0.9 kg (n=2345). Basal and premixed insulin were the most common types of insulin initiated and in most patients no changes were made to the initial regimen over 6 months. However, few patients achieved glycemic control targets.

Short-term outcomes of an employer-sponsored diabetes management program at an ambulatory care pharmacy clinic

The impact of a collaborative, employer-sponsored diabetes management program on glycemic control and other clinical endpoints over 6-12 months is reported. In a retrospective, chart-based evaluation, glycosylated hemoglobin (HbA(1c)) and related health status indicators were assessed among first-year enrollees in the Healthy Outcome Partnership for Employees (HOPE) with Diabetes Program, an ongoing program sponsored by the Wake Forest Baptist Health (WFBH) system. Diabetes management services were provided by pharmacists in collaboration with providers inside and outside the WFBH system. The primary endpoint was the mean change in HbA(1c) during follow-up averaging 8.2 months; secondary endpoints included changes in blood pressure, cholesterol, and triglyceride levels. Among the 98 patients included in the data analysis (75.5% women, 72.4% Caucasian), the mean HbA(1c) value decreased significantly during the study period (from 7.8% to 7.1%, p < 0.01); the proportion of patients at the recommended goal of an HbA(1c) of ≤7.0% rose from 40.8% to 56.1% (p < 0.01). HOPE Program enrollees also experienced significant improvements in mean triglyceride, total cholesterol, and blood pressure values (p < 0.05 for all). A subgroup of patients with initially poor glycemic control (HbA(1c) of ≥8.0%) had a mean HbA(1c) reduction of 1.7 percentage points during the study (p < 0.01), suggesting that the greatest benefits occurred in the highest-risk patients. Among patients seen for at least six months at an employer-sponsored ambulatory care diabetes clinic managed by pharmacists, significant improvements from baseline in clinical end-points including HbA(1c) and blood pressure were demonstrated.

ROSES: role of self‐monitoring of blood glucose and intensive education in patients with Type 2 diabetes not receiving insulin. A pilot randomized clinical trial

To estimate the efficacy of a self-monitoring-based disease management strategy in patients with Type 2 diabetes treated with oral agent monotherapy. This was an open-label, randomized, pilot study, primarily led by diabetes nurses. Patients were randomly allocated to either a self-monitoring-based disease management strategy or usual care (ratio 3:1) and followed up for 6 months. Education was centred on how to modify lifestyle according self-monitoring readings. Self-monitoring of blood glucose results were discussed during monthly telephone contact. The primary endpoint was mean change in HbA(1c) levels, estimated with an ANOVA for repeated measures. All analyses were intention to treat. Three diabetic clinics recruited 62 patients, of whom five were lost to follow-up. At baseline, both groups had a mean HbA(1c) value of 7.9% ± 0.6% (63 ± 6 mmol/mol). After 6 months, mean HbA(1c) reduction was 1.2 ± 0.1% (-13 ± 1 mmol/mol) in the intervention group and 0.7 ± 0.2 (-8 ± 2 mmol/mol) in the control group, with an absolute mean difference between groups of -0.5% (95% CI -0.9 to -0.0%; P = 0.04) (-5 mmol/mol, 95% CI -10 to 0). At study end, 61.9% of patients in the intervention group and 20.0% in the control group reached the target level of HbA(1c) < 7.0% (< 53 mmol/mol) (P = 0.005). Body weight reduction was significantly greater in the intervention group than in the control group (between-group absolute mean difference: -3.99 kg; 95% CI -7.26 to -0.73; P = 0.02). Therapy changes were more frequent in the control group. A self-monitoring disease management strategy, primarily led by diabetes nurses and allowing a timely and efficient use of self-monitoring readings, is able to improve metabolic control, primarily through lifestyle modifications leading to weight loss.

Efficacy and safety of treatment with sitagliptin or glimepiride in patients with type 2 diabetes inadequately controlled on metformin monotherapy: a randomized, double-blind, non-inferiority trial

to evaluate the efficacy and safety of adding sitagliptin or glimepiride to the treatment regimen of patients with type 2 diabetes mellitus and inadequate glycaemic control on metformin monotherapy. patients with type 2 diabetes and an HbA(1c) of 6.5-9.0% while on a stable dose of metformin (≥ 1500 mg/day) combined with diet and exercise for at least 12 weeks were randomized in a double-blind manner to receive either sitagliptin 100 mg daily (N = 516) or glimepiride (starting dose 1 mg/day and up-titrated, based upon patient's self-monitoring of blood glucose results, to a maximum dose of up to 6 mg/day) (N = 519) for 30 weeks. The primary analysis assessed whether sitagliptin is non-inferior to glimepiride in reducing HbA(1c) at week 30 (based on the criterion of having an upper bound of the 95% CI less than the prespecified non-inferiority bound of 0.4%). the mean baseline HbA(1c) was 7.5% in both the sitagliptin group (n = 443) and the glimepiride group (n = 436). After 30 weeks, the least squares (LS) mean change in HbA(1c) from baseline was -0.47% with sitagliptin and -0.54% with glimepiride, with a between-group difference (95% CI) of 0.07% (-0.03, 0.16). This result met the prespecified criterion for declaring non-inferiority. The percentages of patients with an HbA(1c) < 7.0% at week 30 were 52 and 60% in the sitagliptin and glimepiride groups, respectively. The LS mean change in fasting plasma glucose from baseline (95% CI) was -0.8 mmol/l (-1.0, -0.6) with sitagliptin and -1.0 mmol/l (-1.2, -0.8) with glimepiride, for a between-group difference (95% CI) of 0.2 mmol/l (-0.1, 0.4). The percentages of patients for whom hypoglycaemia was reported were 7% in the sitagliptin group and 22% in the glimepiride group (percentage-point difference = -15, p < 0.001). Relative to baseline, sitagliptin was associated with a mean weight loss (-0.8 kg), whereas glimepiride was associated with a mean weight gain (1.2 kg), yielding a between-group difference of -2.0 kg (p < 0.001). in patients with type 2 diabetes and inadequate glycaemic control on metformin monotherapy, the addition of sitagliptin or glimepiride led to similar improvement in glycaemic control after 30 weeks. Sitagliptin was generally well tolerated. Compared to treatment with glimepiride, treatment with sitagliptin was associated with a lower risk of hypoglycaemia and with weight loss versus weight gain (ClinicalTrials.gov: NCT00701090).

Effects of Aerobic and Resistance Training on Hemoglobin A1cLevels in Patients With Type 2 Diabetes

Exercise guidelines for individuals with diabetes include both aerobic and resistance training although few studies have directly examined this exercise combination. To examine the benefits of aerobic training alone, resistance training alone, and a combination of both on hemoglobin A(1c) (HbA(1c)) in individuals with type 2 diabetes. A randomized controlled trial in which 262 sedentary men and women in Louisiana with type 2 diabetes and HbA(1c) levels of 6.5% or higher were enrolled in the 9-month exercise program between April 2007 and August 2009. Forty-one participants were assigned to the nonexercise control group, 73 to resistance training 3 days a week, 72 to aerobic exercise in which they expended 12 kcal/kg per week; and 76 to combined aerobic and resistance training in which they expended 10 kcal/kg per week and engaged in resistance training twice a week. Main Outcome Change in HbA(1c) level. Secondary outcomes included measures of anthropometry and fitness. The study included 63.0% women and 47.3% nonwhite participants who were a mean (SD) age of 55.8 years (8.7 years) with a baseline HbA(1c) level of 7.7% (1.0%). Compared with the control group, the absolute mean change in HbA(1c) in the combination training exercise group was -0.34% (95% confidence interval [CI], -0.64% to -0.03%; P = .03). The mean changes in HbA(1c) were not statistically significant in either the resistance training (-0.16%; 95% CI, -0.46% to 0.15%; P = .32) or the aerobic (-0.24%; 95% CI, -0.55% to 0.07%; P = .14) groups compared with the control group. Only the combination exercise group improved maximum oxygen consumption (mean, 1.0 mL/kg per min; 95% CI, 0.5-1.5, P < .05) compared with the control group. All exercise groups reduced waist circumference from -1.9 to -2.8 cm compared with the control group. The resistance training group lost a mean of -1.4 kg fat mass (95% CI, -2.0 to -0.7 kg; P < .05) and combination training group lost a mean of -1.7 (-2.3 to -1.1 kg; P < .05) compared with the control group. Among patients with type 2 diabetes mellitus, a combination of aerobic and resistance training compared with the nonexercise control group improved HbA(1c) levels. This was not achieved by aerobic or resistance training alone. clinicaltrials.gov Identifier: NCT00458133.

Efficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus

Dipeptidyl peptidase-4 inhibitors improve glycaemic control in patients with type 2 diabetes mellitus when used as monotherapy or in combination with other anti-diabetic drugs (metformin, sulphonylurea, or thiazolidinedione). This 18-week, phase 3b, multicentre, double-blind, noninferiority trial compared the efficacy and safety of two dipeptidyl peptidase-4 inhibitors, saxagliptin and sitagliptin, in patients whose glycaemia was inadequately controlled with metformin. Adult type 2 diabetes mellitus patients (N = 801) with glycated haemoglobin (HbA(1c)) 6.5-10% on stable metformin doses (1500-3000 mg/day) were randomized 1 : 1 to add-on 5 mg saxagliptin or 100 mg sitagliptin once daily for 18 weeks. The primary efficacy analysis was a comparison of the change from baseline HbA(1c) at week 18 in per-protocol patients. Noninferiority was concluded if the upper limit of the two-sided 95% confidence interval of the HbA(1c) difference between treatments was < 0.3%. The adjusted mean changes in HbA(1c) following the addition of saxagliptin or sitagliptin to stable metformin therapy were - 0.52 and - 0.62%, respectively. The between-group difference was 0.09% (95% confidence interval, - 0.01 to 0.20%), demonstrating noninferiority. Both treatments were generally well tolerated; incidence and types of adverse events were comparable between groups. Hypoglycaemic events, mostly mild, were reported in approximately 3% of patients in each treatment group. Body weight declined by a mean of 0.4 kg in both groups. Saxagliptin added to metformin therapy was effective in improving glycaemic control in patients with type 2 diabetes mellitus inadequately controlled by metformin alone; saxagliptin plus metformin was noninferior to sitagliptin plus metformin, and was generally well tolerated.

Effect of Noninsulin Antidiabetic Drugs Added to Metformin Therapy on Glycemic Control, Weight Gain, and Hypoglycemia in Type 2 Diabetes

Metformin is the recommended initial drug therapy for patients with type 2 diabetes mellitus (DM). However, the optimal second-line drug when metformin monotherapy fails is unclear. To determine the comparative efficacy, risk of weight gain, and hypoglycemia associated with noninsulin antidiabetic drugs in patients with type 2 DM not controlled by metformin alone. A literature search via MEDLINE (beginning in January 1950) and Cochrane CENTRAL through January 2010 and a manual search of references for additional relevant studies. Randomized controlled trials (RCTs) with at least 3 months' duration, evaluating noninsulin antidiabetic drugs added to metformin in patients experiencing an inadequate response to maximized and stable (> or = 4 weeks at > or = 1500 mg or maximally tolerated dose) metformin therapy. Inclusion/exclusion criteria; duration of patient follow-up; drug, dose, and schedule used; use of concurrent lifestyle modification; and baseline characteristics (age, sex, anthropometrics, glycated hemoglobin A(1c) [HbA(1c)], duration of DM, and metformin dose). End points collected included mean change in HbA(1c), proportion of patients achieving HbA(1c) goal of less than 7%, change in weight, and incidence of hypoglycemia. Mixed-treatment comparison meta-analysis was used to calculate the weighted mean difference for changes from baseline in HbA(1c) and body weight and relative risk (RR) of HbA(1c) goal attainment and hypoglycemia, with associated 95% credible intervals. Overall, 27 RCTs (n = 11 198) were included. Mean (range) trial duration was 32 (12-52) weeks. The different classes of drugs were associated with similar HbA(1c) reductions (range, 0.64%-0.97%) compared with placebo. Although use of thiazolidinediones, sulfonylureas, and glinides were associated with weight gain (range, 1.77-2.08 kg), glucagon-like peptide-1 analogs, alpha-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors were associated with weight loss or no weight change. Sulfonylureas and glinides were associated with higher rates of hypoglycemia than with placebo (RR range, 4.57-7.50). When added to maximal metformin therapy, all noninsulin antidiabetic drugs were associated with similar HbA(1c) reductions but differed in their associations with weight gain and risk of hypoglycemia.

Safety and efficacy of treatment with sitagliptin or glipizide in patients with type 2 diabetes inadequately controlled on metformin: a 2-year study

To evaluate the 2-year safety and efficacy of adding sitagliptin or glipizide to ongoing metformin in patients with type 2 diabetes. Patients who were on a stable dose of metformin (> or = 1500 mg/day) for at least 8 weeks were randomised in a double-blind manner to receive either sitagliptin 100 mg q.d. (N = 588) or glipizide 5 mg/day (up-titrated up to 20 mg/day based upon prespecified glycaemic criteria) (N = 584). The efficacy analysis assessed the change in HbA(1c) from baseline using the per-protocol (PP) population. For the PP cohort, mean baseline HbA(1c) was 7.3% in both groups. After 2 years, the least squares (LS) mean change in HbA(1c) from baseline [95% confidence interval (CI)] was -0.54% (-0.64, -0.45) with sitagliptin (n = 248) and -0.51% (-0.60, -0.42) with glipizide (n = 256). The rise in HbA(1c) from week 24 to week 104 [i.e. coefficient of durability (COD)] was smaller with sitagliptin [COD (95% CI) 0.16%/year (0.10, 0.21)] compared with glipizide [0.26%/year (0.21, 0.31)]. The proportion of patients with an HbA(1c)< 7% was 63% and 59% with sitagliptin and glipizide, respectively. The beta-cell responsiveness to a meal challenge was maintained with sitagliptin and decreased with glipizide. The proportion of patients who reported hypoglycaemia was 5% with sitagliptin and 34% with glipizide [difference in proportions (95% CI) = -29% (-33, -25)]. Relative to baseline, sitagliptin was associated with weight loss (-1.6 kg) compared with weight gain (+0.7 kg) with glipizide. In patients with type 2 diabetes, adding sitagliptin to metformin monotherapy improved glycaemic control over 2 years, similar to the glucose-lowering efficacy observed with adding glipizide, but with greater durability and generally better maintenance of beta-cell function. Sitagliptin was generally well tolerated with a lower risk of hypoglycaemia and weight loss compared with weight gain observed with glipizide.

Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes

The aim of this study was to compare efficacy and tolerability of initial combination therapy with vildagliptin/pioglitazone to component monotherapy. This 24-week, multicentre, randomized, double-blind, active-controlled study assessed the effects of the dipeptidyl peptidase-4 inhibitor vildagliptin (100 mg q.d.), pioglitazone (30 mg q.d.) and vildagliptin combined with pioglitazone (100/30 mg q.d. or 50/15 mg q.d.) in 607 drug-naive patients with type 2 diabetes (T2DM). The primary outcome measure was change from baseline in HbA(1c) in patients receiving initial combination therapy compared with pioglitazone monotherapy. After 24-week treatment, adjusted mean changes in HbA(1c) from baseline (approximately 8.7%) in patients receiving pioglitazone monotherapy, 50/15 mg combination, 100/30 mg combination and vildagliptin monotherapy were -1.4 +/- 0.1%, -1.7 +/- 0.1%, -1.9 +/- 0.1% and -1.1 +/- 0.1% respectively. Both low-dose and high-dose combinations were significantly more efficacious than pioglitazone alone (p = 0.039 and p < 0.001 respectively). Adjusted mean changes in fasting plasma glucose were -1.9 +/- 0.2, -2.4 +/- 0.2, -2.8 +/- 0.2 and -1.3 +/- 0.2 mmol/l respectively, and both combination groups were significantly more effective than pioglitazone monotherapy (p = 0.022 and p < 0.001 respectively). The overall incidence of adverse events ranged from 45.8% in the low-dose combination to 51.6% in the pioglitazone monotherapy group. The incidence of peripheral oedema was highest in patients receiving pioglitazone monotherapy (9.3%) and lowest in those receiving low-dose combination (3.5%). One mild hypoglycaemic event was reported by one patient receiving high-dose combination and one patient receiving vildagliptin monotherapy. First-line treatment with vildagliptin/pioglitazone combination in patients with T2DM provides better glycaemic control than either monotherapy component yet has minimal risk of hypoglycaemia and a tolerability profile comparable with component monotherapy.

A comparison of glycaemic and metabolic control over time among South Asian and European patients with Type 2 diabetes: results from follow‐up in a routine diabetes clinic

Although South Asians have a higher prevalence of diabetes which develops at a younger age, data on change in metabolic parameters post-diagnosis are relatively sparse. We therefore wished to determine whether South Asians with diabetes had similar or greater year-on-year deterioration in metabolic parameters compared with Europeans. We analysed longitudinal change in metabolic parameters [glycated haemoglobin (HbA(1c)), blood pressure, body mass index (BMI), lipids] among South Asian (n = 210) and European (n = 1557) patients consecutively attending the same diabetes clinic over a mean period of 5.3 years. South Asians were younger than Europeans at first recorded diagnosis of diabetes (mean age 45.9 vs. 57.3 years, P < 0.001) and had significantly lower ( approximately 1.2 units) BMI and blood pressure. Mean HbA(1c) was not different across ethnic groups at first visit, but with time glycaemic control was worse in South Asians than Europeans, with average deterioration 1.31% (= 0.23%/year) in Asians vs. 0.82% (0.16%/year) in Europeans, P = 0.003. This ethnic difference in mean change in HbA(1c) persisted after adjustment for age, sex, baseline HbA(1c), and weight change in linear regression analysis (beta = 0.46, 95% CI 0.24-0.69, P < 0.001), and with additional adjustment for time to referral and duration of diabetes (P = 0.01). Moreover, South Asians had significantly smaller improvements in blood pressure (P < 0.001) and cholesterol (P = 0.044) over the follow-up period in keeping with fewer prescriptions of anti-hypertensive agents and lipid-lowering agents. These data suggest the need to be more aggressive in the management of diabetes and related risk factors in South Asians.