Glycemic Control Reduction Research Articles

Telephone-Delivered Behavioral Skills Intervention for African American Adults with Type 2 Diabetes: A Randomized Controlled Trial

Diabetes disproportionately affects African Americans and is associated with poorer outcomes. Self-management is important for glycemic control; however, evidence in African Americans is limited. To assess the efficacy of a combined telephone-delivered education and behavioral skills intervention (TBSI) in reducing hemoglobin A1c (HbA1c) levels in African Americans with type 2 diabetes, using a factorial design. This is afour-year randomized clinical trial, using a 2 x 2 factorial design.: Participants: African American adults ≥18years) with poorly controlled type 2 diabetes (HbA1c ≥9%) were randomly assigned to one of four groups: 1) knowledge only, 2) skills only, 3) combined knowledge and skills (TBSI), or 4) control group. All participants received 12 telephone-delivered 30-min intervention sessions specific to their assigned group. Participants were assessed at baseline and 3, 6, and 12months. The primary outcome was HbA1c at 12 months post-randomization in the intent-to-treat (ITT) population. Two hundred fifty-five participants were randomly assigned to the four groups. Based on the ITT population after multiple imputation, the analysis of covariance with baseline HbA1c as the covariate showed that HbA1c at 12months for the intervention groups did not differ significantly from that of the control group (knowledge: 0.49, p = 0.123; skills: 0.23, p = 0.456; combined: 0.48, p = 0.105). Absolute change from baseline at 12months for all treatment arms was 0.6. Longitudinal mixed effects analysis showed that, on average, there was a significant decline in HbA1c over time for all treatment groups (-0.07, p < 0.001). However, the rates of decline for the intervention groups were not significantly different from that of the control group (knowledge: 0.06, p = 0.052; skills: 0.02, p = 0.448; combined: 0.05, p = 0.062). Results from per-protocol populations were similar. For African Americans with poorly controlled type 2 diabetes, combined education and skills training did not achieve greater reductions in glycemic control (i.e., HbA1c levels) at 12months compared to the control group, education alone, or skills training alone. This trial is registered with ClinicalTrials.gov, identifier no. NCT00929838.

Effect of pioglitazone on plasma ceramides in adults with metabolic syndrome.

Metabolic syndrome (MetS) appears closely linked with ceramide accumulation, inducing insulin resistance and toxicity to multiple cell types. Animal studies demonstrate that thiazolidinediones (TZDs) reduce ceramide concentrations in plasma and skeletal muscle and support lowering of ceramide levels as a potential mediator of TZDs' mechanism of action in reducing insulin resistance; however, studies in humans have yet to be reported. This study investigated the effects of pioglitazone therapy on plasma ceramides to understand the mechanism by which TZDs improve insulin resistance in MetS. Thirty-seven subjects with MetS were studied in a single-centre, randomized, double-blind, placebo-controlled trial comparing pioglitazone to placebo. Data were collected at baseline and after 6 months of therapy. The primary endpoint was the change from baseline in plasma ceramide concentrations. Treatment with pioglitazone for 6 months, compared with placebo, significantly reduced multiple plasma ceramide concentrations: C18:0 (p = 0.001), C20:0 (p = 0.0004), C24 : 1 (p = 0.009), dihydroceramide C18 :0 (p = 0.005), dihydroceramide C24:1 (p = 0.004), lactosylceramide C16:0 (p = 0.02) and the hexosylceramides C16:0 (p = 0.0003), C18 : 0 (p = 0.00001), C22:0 (p = 0.00002) and C24:1 (p = 0.0006). Additionally, significant reductions were found when ceramides were grouped by species: ceramides (p = 0.03), dihydroceramides (p = 0.02), hexosylceramides (p = 0.00001) and lactosylceramides (p = 0.02). The total of all measured ceramides was also significantly reduced (p = 0.001). Following treatment with pioglitazone, the decrease in some ceramide species correlated negatively with the change in insulin sensitivity (dihydroceramide C16:0, r = -0.54; p = 0.02) and positively with total (lactosylceramide C24:0, r = 0.53; p = 0.02) and high molecular weight (lactosylceramide C24:0, r = 0.48; p = 0.05) adiponectin measurements; however, significant associations with changes in liver fat and glycemic control reduction were not found. Pioglitazone in individuals with MetS induces a potent decrease in plasma ceramides, and some of the changes correlate with changes in insulin resistance and adiponectin levels.

Efficacy and safety of canagliflozin alone or as add-on to other oral antihyperglycemic drugs in Japanese patients with type 2 diabetes: A 52-week open-label study.

Aims/IntroductionCanagliflozin is a sodium–glucose cotransporter 2 inhibitor under development for the treatment of type 2 diabetes. Our aim was to examine its efficacy and safety as monotherapy or in combination with commonly used oral antihyperglycemic drugs in Japanese patients with type 2 diabetes.Materials and MethodsPatients on diet/exercise alone or diet/exercise plus an oral antihyperglycemic drug (sulfonylurea, glinide, α-glucosidase inhibitor, biguanide, thiazolidinedione or dipeptidyl peptidase-4 inhibitor) were randomized to either 100 or 200 mg canagliflozin while continuing prior therapy. Patients were treated for 52 weeks in an open-label manner.ResultsCanagliflozin significantly reduced hemoglobin A1c, fasting plasma glucose and bodyweight in all the study groups. Improvements were apparent by 4 weeks of treatment, and were maintained for 52 weeks. The reduction in hemoglobin A1c ranged from −0.80 to −1.06%, and from −0.93 to −1.26% in the 100 and 200 mg canagliflozin groups, respectively. Drug-related adverse events occurred in approximately one-third of patients, and included hypoglycemia/asymptomatic hypoglycemia and pollakiuria. Hypoglycemia/asymptomatic hypoglycemia was most common in patients treated with a sulfonylurea. Most adverse events were classified as mild or moderate in severity.ConclusionsThe results of the present study confirmed that treatment with canagliflozin resulted in significant reductions in glycemic control and bodyweight that were maintained for 52 weeks of treatment irrespective of whether it was administered as monotherapy or in combination with another oral antihyperglycemic drug. Canagliflozin was well tolerated, with a low incidence of drug-related adverse events. This trial was registered with ClinicalTrials.gov (no. NCT01387737).

Effectiveness of Liraglutide in Type 2 Diabetes Patients Switched from a DPP-4 Inhibitor: 1-Year Data from EVIDENCE®

Here we assess the effectiveness of 1 year’s treatment with liraglutide in patients with type 2 diabetes who switched from a DPP-4 inhibitor (DPP-4i) in EVIDENCE® study; a multicentre, observational, post-marketing outpatient study requested by the French National Health Authority to evaluate the effectiveness and safety of liraglutide. Objective: to determine percentage patients still taking liraglutide and at A1C target (<7%) after 2 years. Of 3137 patients enrolled, 1255 (40%) were receiving a DPP-4i prior to liraglutide initiation. Thirty-two percent (n=1004) switched to liraglutide at study start, while 8% (n=251) added liraglutide to a DPP-4i. Patients who switched and continued liraglutide for 1 year (n=734) achieved significant reductions from baseline in mean A1C (–0.84%, p<0.0001), fasting plasma glucose (–0.27g/L, p<0.0001) and weight (–3.53kg, p<0.0001). More subjects had A1C<7% at 1 year (31.6%) vs. baseline (8.0%; p<0.0001). Withdrawals (30% overall) were mostly due to gastrointestinal disorders experienced early in the study. In conclusion, significant reductions in glycemic control and weight were observed after 1 year of liraglutide treatment in patients who switched from a DPP-4i at study start. Lack of a control arm makes it difficult to evaluate whether observed improvements are attributable to liraglutide alone. Switching from the DPP-4i sitagliptin to liraglutide in a randomized controlled trial (Pratley et al. 2012) provided significant A1C (–0.5%; p<0.0001) and body weight reductions (–2.5 kg; p<0.0001). EVIDENCE® is more representative of routine practice; results reported here may be more indicative of real-world liraglutide treatment outcomes.TableBaseline characteristics of patients switching from a DPP-4i to liraglutideBaseline characteristicsn1004Age, years58 ± 10Diabetes duration, years9.8 ± 6.3A1C, %8.5 ± 1.4Patients with A1C <7%, %8%Fasting plasma glucose, g/L1.8 ± 0.6Weight, kg95 ± 18BMI, kg/m234 ± 6Data are mean ± SD. Open table in a new tab Data are mean ± SD.

Effectiveness and Tolerability of Liraglutide Among Type 2 Diabetes Patients in Routine Clinical Practice: 1-Year Data from EVIDENCE®

observational, post-marketing outpatient study requested by the French National Health Authority to evaluate the effectiveness and safety of liraglutide. Objective: to determine percentage patients still taking liraglutide and at A1C target (<7%) after 2 years. Of 3137 patients enrolled, 1255 (40%) were receiving a DPP-4i prior to liraglutide initiation. Thirty-two percent (n1⁄41004) switched to liraglutide at study start, while 8% (n1⁄4251) added liraglutide to a DPP-4i. Patients who switched and continued liraglutide for 1 year (n1⁄4734) achieved significant reductions from baseline in mean A1C (e0.84%, p<0.0001), fasting plasma glucose (e0.27g/L, p<0.0001) and weight (e3.53kg, p<0.0001). More subjects had A1C<7% at 1 year (31.6%) vs. baseline (8.0%; p<0.0001). Withdrawals (30% overall) were mostly due to gastrointestinal disorders experienced early in the study. In conclusion, significant reductions in glycemic control and weight were observed after 1 year of liraglutide treatment in patients who switched from a DPP-4i at study start. Lack of a control arm makes it difficult to evaluate whether observed improvements are attributable to liraglutide alone. Switching from the DPP-4i sitagliptin to liraglutide in a randomized controlled trial (Pratley et al. 2012) provided significant A1C (e0.5%; p<0.0001) and body weight reductions (e2.5 kg; p<0.0001). EVIDENCE is more representative of routine practice; results reported here may be more indicative of real-world liraglutide treatment outcomes.

Use of Continuous Glucose Monitoring in Subjects With Type 1 Diabetes on Multiple Daily Injections Versus Continuous Subcutaneous Insulin Infusion Therapy

OBJECTIVETo compare use of continuous glucose monitoring in subjects with type 1 diabetes on multiple daily injection (MDI) therapy versus continuous subcutaneous insulin infusion (CSII) therapy for 6 months.RESEARCH DESIGN AND METHODSSixty type 1 diabetic adults with similar baseline characteristics, using either MDI (n = 30) or CSII (n = 30) therapy, were enrolled in this 6-month prospective study. Subjects were instructed to wear the DexCom SevenPLUS continuous glucose monitor at all times throughout the study. All subjects were initially blinded from the continuous glucose monitoring (CGM) glucose data. After 4 weeks of blinded CGM use, the CGM was unblinded, making glucose data available to the patient. The CGM remained in the unblinded state for the remainder of the study (20 weeks). Clinic visits occurred every 4 weeks, at which time A1C values were collected and CGM data were downloaded.RESULTSMean baseline (± SD) A1C was 7.61 (± 0.76) and 7.63 (± 0.68) for CSII and MDI, respectively (P > 0.05). Without any significant therapy change, A1C decrease at 12 weeks was similar in both groups (P = 0.03). When compared with the blinded phase, unblinded use of CGM was associated with similar but significant reductions in glycemic control and variability parameters. In addition, both therapy groups had similar changes in mean glucose and glucose variability indexes at 3 and 6 months (ITT analysis, P > 0.05). Predefined per protocol analysis (sensor use at least 6 days/week) showed greater improvement in time spent in target range glycemia, 3.9–10.0 mmol/L (70–180 mg/dL), in the CSII group.CONCLUSIONSWe conclude that CGM provides similar benefits in glucose control for patients using MDI or CSII therapy.

Insulin glargine-based therapy improves glycemic control in patients with type 2 diabetes sub-optimally controlled on premixed insulin therapies

The AT.LANTUS trial recently demonstrated the efficacy and safety of insulin glargine initiation and maintenance using two different treatment algorithms in poorly controlled type 2 diabetes mellitus (T2DM). This sub-analysis investigated glycemic control and safety in 686 patients switching from premixed insulin (premix) with or without (±OADs) to once-daily glargine (±OADs/prandial insulin). A 24-week, multinational ( n = 59), multicenter ( n = 611), randomized study comparing two algorithms (Algorithm 1: clinic-driven titration; Algorithm 2: patient-driven titration) in four glargine ± OADs treatment groups: alone, once- (OD), twice- (BD) or >twice- (>BD) daily prandial insulin. After switching to the glargine regimen, HbA 1c levels significantly improved in the overall group (9.0 ± 1.3 to 8.0 ± 1.2%; p < 0.001) and in all subgroups; fasting blood glucose levels also improved in all subgroups (overall: 167.1 ± 50.0 to 106.9 ± 27.2 mg/dL [9.3 ± 2.8 to 5.9 ± 1.5 mmol/L]; p < 0.001). The incidence of severe hypoglycemia was also low in all four subgroups (≤1.7%). Patients with T2DM switching from premix ± OADs to glargine ± OADs had significant reductions in glycemic control with a low incidence of severe hypoglycemia. The addition of prandial (OD, BD or >BD) insulin was associated with further improvements in glycemic control. These data provide support for the stepwise introduction of prandial insulin to a more physiologic basal–bolus regimen, which is under investigation.

Exenatide effects on glucose metabolism and metabolic disorders common to overweight and obese patients with type 2 diabetes

AbstractThe risks of cardiovascular disease (CVD) and type 2 diabetes increase as body mass index increases in overweight (25–30 kg/m2) and obese (&gt;30 kg/m2) individuals. However, these risks can be reduced with even modest weight loss. In patients with established type 2 diabetes, control of both glycemia and body weight are important to minimize the risk of future diabetic complications. Exenatide is a 39‐amino‐acid peptide incretin mimetic currently approved in the United States for the treatment of type 2 diabetes as an adjunct to sulfonylurea and/or metformin. Phase‐3 clinical studies showed exenatide therapy for 30 weeks significantly reduced glycosylated hemoglobin (HbA1c), and fasting and postprandial plasma glucose, while significantly reducing body weight. Open‐label extensions from these pivotal trials demonstrated patients treated with exenatide for 2 years had sustained reductions in glycemic control at 30 weeks and a progressive reduction in body weight. Patients treated with exenatide also had improvement in blood pressure, inflammatory markers, and lipid profiles. The glucoregulatory and weight‐reducing effects of exenatide are the result of multiple modes of action that mimic several of the glucoregulatory actions of the naturally occurring peptide, glucagon‐like peptide‐1 (GLP‐1). These include restoration of first phase insulin response, enhancement of glucose‐dependent insulin secretion, suppression of inappropriate glucagon secretion, slowing of gastric emptying, and affects on satiety leading to reduced food intake. Further research is required to fully understand the role for exenatide to potentially alleviate metabolic disorders associated with type 2 diabetes, including CVD and obesity. Drug Dev. Res. 67:666–676, 2006. © 2006 Wiley‐Liss, Inc.

Insulin versus oral agents in the management of Cystic Fibrosis Related Diabetes: a case based study

BackgroundInsulin is the recommend therapeutic agent of choice for the management of Cystic Fibrosis Related Diabetes (CFRD), despite only sub-optimal reductions in glycemic control and increased morbidity and mortality reported by centers using this agent. The newer insulin sensitizing agents demonstrated to have anti-inflammatory mechanisms may provide an alternative management option for CFRD.MethodsA prospective case based therapeutic comparison between insulin, sulfonylurea, metformin and thiazolidinedione was observed over one decade with 20 CFRD patients diagnosed using American Diabetes Association guideline standards. Patients entering the study elected treatment based on risk and benefit information provided for treatment options. Patients receiving organ transplant or requiring combination diabetic medications were excluded from the study.ResultsNo statistical advantage was achieved regarding overall glycemic control for oral agents over insulin. Additional outcome measures including changes in weight, liver function testing and FEV1 were not statistically significant.ConclusionInsulin alone may not be the only therapeutic option in managing CFRD. Oral hypoglycemic agents were equally effective in treating CFRD and may provide an alternative class of agents for patients reluctant in using insulin.