Insulin Glargine Group Research Articles

Efficacy of exenatide and insulin glargine on nonalcoholic fatty liver disease in patients with type 2 diabetes.

The aim of this study was to investigate the efficacy of exenatide and insulin glargine in patients with newly diagnosed type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). We performed a 24-week randomized controlled multicentre clinical trial. Seventy-six patients were randomly assigned 1:1 to receive exenatide or insulin glargine treatment. The endpoints included changes in liver fat content (LFC), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) measured by magnetic resonance spectroscopy, blood glucose, liver enzymes, lipid profile, body weight, and Fibrosis-4 index (FIB-4). LFC, VAT, SAT, and FIB-4 were significantly reduced after exenatide treatment (ΔLFC, -17.55 ± 12.93%; ΔVAT, -43.57 ± 68.20 cm2 ; ΔSAT, -28.44 ± 51.48 cm2 ; ΔFIB-4, -0.10 ± 0.26; all P < .05). In comparison, only LFC (ΔLFC, -10.49 ± 11.38%; P < .05), and not VAT, SAT, or FIB-4 index (all P > .05), was reduced after insulin glargine treatment. Moreover, exenatide treatment resulted in greater reductions in alanine transaminase (ALT), aspartate transaminase (AST), and gamma glutamyl transpeptidase (GGT) than insulin glargine (P < 0.05). The body weight, waist circumference, postprandial plasma glucose, and low-density lipoprotein cholesterol (LDL-C) in the exenatide group also presented greater reductions than the insulin glargine group (P < .05). The proportion of adverse events were comparable between the two groups. Both exenatide and insulin glargine reduced LFC in patients with drug-naive T2DM and NAFLD; however, exenatide showed greater reductions in body weight, visceral fat area, liver enzymes, FIB-4, postprandial plasma glucose, and LDL-C.

(Ultra-)long-acting insulin analogues for people with type 1 diabetes mellitus

(Ultra-)long-acting insulin analogues for people with type 1 diabetes mellitus

Weight loss in patients with type 2 diabetes receiving once-weekly dulaglutide plus insulin lispro or insulin glargine plus insulin lispro: A post-hoc analysis of the AWARD-4 study across baseline body mass index subgroups.

Insulin-treated patients with type 2 diabetes (T2D) and obesity are challenged in achieving body weight stability or reduction, in addition to glycaemic control. Post-hoc analyses of body weight and insulin dose data from the AWARD-4 trial involved comparison of treatment with once-weekly dulaglutide 1.5 mg (N = 295) or 0.75 mg (N = 293) and treatment with daily insulin glargine (N = 296), each with prandial insulin lispro (± metformin). Changes in weight and in the proportion of patients without weight gain or with weight loss of at least 3%, 5% or 10% or composites of HbA1c less than 7% without weight gain and weight loss of at least 3% after 52 weeks were compared between the dulaglutide (either dose) groups and the insulin glargine group, overall and by baseline BMI (<30, 30-<35, ≥35 kg/m2 ), using analysis of covariance and logistic regression, including interaction terms. The following parameters were statistically significant (P < 0.01) in favour of the dulaglutide-treated groups, at lower mean total daily insulin doses, vs the insulin glargine group. The achieved targets were more pronounced with dulaglutide 1.5 mg than with insulin glargine: LSM weight change difference, -3.23 kg; proportion of patients without weight gain, 49.0% vs 19.0%; proportion of patients with weight loss ≥3%, 21.7% vs 5.7% or with weight loss ≥5%, 10.5% vs 2.4%; proportion of patients with HbA1c <7% without weight gain, 26.2% vs 7.9%; proportion of patients with HbA1c <7% and weight loss ≥3%, 11.9% vs 1.4%, respectively. Treatment effect for these parameters was not significantly different across BMI categories. Larger proportions of patients in late-stage T2D needing treatment intensification achieved glycemic control without weight gain or with weight loss at lower insulin doses with once-weekly dulaglutide plus daily prandial insulin than with a basal-bolus insulin regimen, overall and across all three BMI subgroups.

Dapagliflozin improves blood glucose in diabetes on triple oral hypoglycemic agents having inadequate glucose control

AimsThe aim of this study was to evaluate whether a combination drug therapy that consists of dapagliflozin with three other oral hypoglycemic agents (OHAs) would have a beneficial safety and efficacy profile in T2DM patients who have uncontrolled glucose levels compared to a treatment regimen that contains of basal insulin with two different OHAs. MethodsA total of 162 type 2 diabetic patients who are unable to control glucose on their current therapy consisting of 3 OHAs were enrolled in dapagliflozin group and 148 patients in insulin glargine group for the 24-week study period. ResultsThe mean changes in HbA1c level were comparable as −0.97 ± 1.29% in dapagliflozin group and −0.95 ± 1.41% in insulin glargine group (p = 0.911). Also, the fasting plasma glucose or post-prandial 2 h glucose were comparably decreased in dapagliflozin or insulin glargine. In terms of the body-weight, there was a significant decrease of −2.36 ± 0.51 kg following treatment of dapagliflozin, whereas the increment of 1.93 ± 0.49 kg was in insulin glargine (p < 0.001). In terms of adverse events, hypoglycemic events were higher in insulin glargine rather than dapagliflozin (15.1% vs. 1.6%, p < 0.05). ConclusionsOur findings demonstrated that the addition of dapagliflozin to an existing drug regimen consisting of three different OHAs in patients exhibiting inadequate blood glucose control could be alternate treatment modality in T2D who hesitate to initiate insulin therapy.

Effect of insulin glargine on recreational physical activity and TV viewing: Analysis of the randomised ORIGIN trial.

To quantify whether insulin therapy, and concomitant weight gain, affects recreational physical activity and TV viewing time using data from the Outcomes Reduction with an Initial Glargine Intervention (ORIGIN) trial. 12,537 insulin-naïve individuals with dysglycaemia were randomised to receive either basal insulin glargine or standard care and followed for a median of 6.2years. Complete recreational physical activity and TV viewing time questionnaires across baseline, 2year follow-up and study end were available for 8954 participants. Differences between groups at follow-up were assessed by analysis of covariance. At follow-up, there was no difference in physical activity or TV viewing time between those taking insulin glargine and those receiving standard care, despite body weight increasing by 1.66 (7.56) kg in the insulin glargine group and reducing by -0.65 (7.90) kg in the standard care group (P<0.001). The dose of insulin glargine was not associated with changes in physical activity. Despite modest weight gain, insulin glargine did not adversely impact recreational physical activity levels within an international cohort with dysglyaemia. ORIGIN ClinicalTrials.gov number: NCT00069784.

Effects of exenatide on cardiac function, perfusion, and energetics in type 2 diabetic patients with cardiomyopathy: a randomized controlled trial against insulin glargine

BackgroundMultiple bloodglucose-lowering agents have been linked to cardiovascular events. Preliminary studies showed improvement in left ventricular (LV) function during glucagon-like peptide-1 receptor agonist administration. Underlying mechanisms, however, are unclear. The purpose of this study was to investigate myocardial perfusion and oxidative metabolism in type 2 diabetic (T2DM) patients with LV systolic dysfunction as compared to healthy controls. Furthermore, effects of 26-weeks of exenatide versus insulin glargine administration on cardiac function, perfusion and oxidative metabolism in T2DM patients with LV dysfunction were explored.Methods and resultsTwenty-six T2DM patients with LV systolic dysfunction (cardiac magnetic resonance (CMR) derived LV ejection fraction (LVEF) of 47 ± 13%) and 10 controls (LVEF of 59 ± 4%, P < 0.01 as compared to patients) were analyzed. Both myocardial perfusion during adenosine-induced hyperemia (P < 0.01), and coronary flow reserve (P < 0.01), measured by [15O]H2O positron emission tomography (PET), were impaired in T2DM patients as compared to healthy controls. Myocardial oxygen consumption and myocardial efficiency, measured using [11C]acetate PET and CMR derived stroke volume, were not different between the groups. Eleven patients in the exenatide group and 12 patients in the insulin glargine group completed the trial. Systemic metabolic control was improved after both treatments, although, no changes in cardiac function, perfusion and metabolism were seen after exenatide or insulin glargine.ConclusionsT2DM patients with LV systolic dysfunction did not have altered myocardial efficiency as compared to healthy controls. Exenatide or insulin glargine had no effects on cardiac function, perfusion or oxidative metabolism.Trial registration NCT00766857

The effect of basal insulin glargine on the fibrinolytic system and von Willebrand factor in people with dysglycaemia and high risk for cardiovascular events: Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial.

Fibrinolytic factors, plasminogen activator inhibitor-1, tissue plasminogen activator, tissue plasminogen activator/plasminogen activator-complex and the haemostatic factor von Willebrand factor are known markers of cardiovascular disease. Their plasma levels are adversely affected in patients with dysglycaemia, and glucose normalization with insulin glargine might improve the levels of these factors. Prespecified Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial (ClinicalTrials.gov number, NCT00069784). Tissue plasminogen activator activity, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor were analysed at study start, after 2 years and at the end of the study (median follow-up of 6.2 years). Of 129 patients (mean age of 64 ± 7 years, females: 19%), 68 (53%) and 61 (47%) were randomized to the insulin glargine and standard care group, respectively. Allocation to insulin glargine did not significantly affect the studied fibrinolytic markers or von Willebrand factor compared to standard care. Likewise, there were no significant differences in plasminogen activator inhibitor-1, tissue plasminogen activator antigen and von Willebrand factor. During the whole study period, the within-group analysis revealed a curvilinear pattern and significant changes for tissue plasminogen activator/plasminogen activator inhibitor-1 complex, tissue plasminogen activator antigen and von Willebrand factor in the insulin glargine but not in the standard care group. In people with dysglycaemia and other cardiovascular risk factors, basal insulin does not improve the levels of markers of fibrinolysis or von Willebrand factor compared to standard glucose-lowering treatments.

Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial

Several pharmacological treatment options are available for type 2 diabetes; however, many patients do not achieve optimum glycaemic control and therefore new therapies are necessary. We assessed the efficacy and safety of semaglutide, a glucagon-like peptide-1 (GLP-1) analogue in clinical development, compared with insulin glargine in patients with type 2 diabetes who were inadequately controlled with metformin (with or without sulfonylureas). We did a randomised, open-label, non-inferiority, parallel-group, multicentre, multinational, phase 3a trial (SUSTAIN 4) at 196 sites in 14 countries. Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea. We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose target of 4·0-5·5 mmol/L [72-99 mg/dL]) for 30 weeks. In all treatment groups, previous background metformin and sulfonylurea treatment was continued throughout the trial. We did the randomisation using an interactive voice or web response system. The primary endpoint was change in mean HbA1c from baseline to week 30 and the confirmatory secondary endpoint was the change in mean bodyweight from baseline to week 30. We assessed efficacy and safety in the modified intention-to-treat population (mITT; all randomly assigned participants who were exposed to at least one dose of study drug) and used a margin of 0·3% to establish non-inferiority in HbA1c reduction. This trial is registered with ClinicalTrials.gov, number NCT02128932. Between Aug 4, 2014, and Sept 3, 2015, we randomly assigned 1089 participants to treatment; the mITT population consisted of 362 participants assigned to 0·5 mg semaglutide, 360 to 1·0 mg semaglutide, and 360 to insulin glargine. 49 (14%) participants assigned to 0·5 mg semaglutide discontinued treatment prematurely, compared with 55 (15%) assigned to 1·0 mg semaglutide, and 26 (7%) assigned to insulin glargine. Most discontinuations were due to adverse events-mostly gastrointestinal with semaglutide, and others such as skin and subcutaneous tissue disorders (eg, rash, pruritus, and urticaria) with insulin glargine. From a mean baseline HbA1c of 8·17% (SD 0·89), at week 30, 0·5 and 1·0 mg semaglutide achieved reductions of 1·21% (95% CI 1·10-1·31) and 1·64% (1·54-1·74), respectively, versus 0·83% (0·73-0·93) with insulin glargine; estimated treatment difference versus insulin glargine -0·38% (95% CI -0·52 to -0·24) with 0·5 mg semaglutide and -0·81% (-0·96 to -0·67) with 1·0 mg semaglutide (both p<0·0001). Mean bodyweight at baseline was 93·45 kg (SD 21·79); at week 30, 0·5 and 1·0 mg semaglutide achieved weight losses of 3·47 kg (95% CI 3·00-3·93) and 5·17 kg (4·71-5·66), respectively, versus a weight gain of 1·15 kg (0·70-1·61) with insulin glargine; estimated treatment difference versus insulin glargine -4·62 kg (95% CI -5·27 to -3·96) with 0·5 mg semaglutide and -6·33 kg (-6·99 to -5·67) with 1·0 mg semaglutide (both p<0·0001). Severe or blood glucose-confirmed hypoglycaemia was reported by 16 (4%) participants with 0·5 mg semaglutide and 20 (6%) with 1·0 mg semaglutide versus 38 (11%) with insulin glargine (p=0·0021 and p=0·0202 for 0·5 mg and 1·0 mg semaglutide vs insulin glargine, respectively). Severe hypoglycaemia was reported by two (<1%) participants with 0·5 mg semaglutide, five (1%) with 1·0 mg semaglutide, and five (1%) with insulin glargine. Six deaths were reported: four (1%) in the 0·5 mg semaglutide group (three cardiovascular deaths, one pancreatic carcinoma, which was assessed as being possibly related to study medication) and two (<1%) in the insulin glargine group (both cardiovascular death). The most frequently reported adverse events were nausea with semaglutide, reported in 77 (21%) patients with 0·5 mg and in 80 (22%) with 1·0 mg, and nasopharyngitis reported in 44 (12%) patients with insulin glargine. Compared with insulin glargine, semaglutide resulted in greater reductions in HbA1c and weight, with fewer hypoglycaemic episodes, and was well tolerated, with a safety profile similar to that of other GLP-1 receptor agonists. Novo Nordisk A/S.

Pharmacological efficacy of FGF21 analogue, liraglutide and insulin glargine in treatment of type 2 diabetes

Fibroblast growth factor 21 (FGF21) is a promising regulator of glucose and lipid metabolism with multiple beneficial effects including hypoglycemic and lipid-lowering. Previous studies have reported that FGF21 is expected to become a new drug for treatment of diabetes. Liraglutide and insulin glargine are the two representative anti-diabetic biological drugs. In the current study, we aim to compare the long-term pharmacological efficacy of mFGF21 (an FGF21 analogue), liraglutide and insulin glargine in type 2 diabetic db/db mice. Db/db mice were initially treated with three kinds of proteins (25nmol/kg/day) by subcutaneous injection once a day for 4weeks, then subsequently be treated with once every two days for next 4weeks. After 8weeks of treatments, the blood glucose levels, body weights, glycosylated hemoglobin levels, fasting insulin levels, serum lipid profiles, hepatic biochemical parameters, oral glucose tolerance tests and hepatic mRNA expression levels of several proteins (GK, G6P, GLUT-1 and GLUT-4) associated with glucose metabolism of the experimental mice were detected. Results demonstrated that three proteins could significantly decrease the fed blood glucose levels of db/db mice. After treatment for 1week, the fed blood glucose levels of db/db mice in liraglutide group were significantly lower than those in mFGF21 and insulin glargine groups. However, after 2weeks of administration, the long-lasting hypoglycemic effect of mFGF21 was superior to liraglutide and insulin glargine up to the end of the experiments. Compared with liraglutide and insulin glargine, mFGF21 significantly reduced the glycosylated hemoglobin levels and improved the ability on glycemic control, insulin resistance, serum lipid and liver function states in db/db mice after 8weeks treatments. In addition, mFGF21 regulated glucose metabolism through increasing the mRNA expression levels of GK and GLUT-1, and decreasing the mRNA expression level of G6P. But liraglutide and insulin glargine could only up-regulate the mRNA expression of GLUT-4. In summary, as a hypoglycemic drug for long-term treatment, mFGF21 has the potential to be an ideal drug candidate for the therapy of type 2 diabetes.

Real-world therapeutic benefits of patients on insulin glargine versus NPH insulin.

The addition of a single injection of insulin to the oral drugs (basal supported oral therapy; BOT) has been shown to greatly reduce blood glucose levels. The intermediate-acting NPH insulin (NPH) and the long-acting insulin glargine (Lantus(®)) have been compared for use in BOT in numerous clinical trials; however, their efficacy and safety in a real-life setting have not been described. TIP (therapeutic benefits of patients on insulin glargine vs. NPH insulin being poorly controlled on prior short-time basal-insulin supported therapy with NPH insulin or insulin glargine) is a non-interventional, multicentre, observational study over 24weeks. A total of 2629 patients were enrolled and 1931 were fully evaluable (1614 insulin glargine, 303 NPH insulin). Propensity scoring (PSM) was used to match 570 patients into 2 similar cohorts of 285 patients. In the PSM cohort, a slightly greater reduction in FBG and HbA1c levels was seen in the insulin glargine group compared to the NPH group. A weight loss, which was slightly more pronounced in insulin glargine patients despite receiving a lower insulin dose relative to the NPH group, was seen in both the groups. Additionally, hypoglycaemia, including nocturnal and severe events, was more prevalent in the patients receiving BOT with NPH. The occurrence of new micro- or macro-vascular complications and adverse events was low for both groups. A large proportion of patients changed from NPH therapy to insulin glargine therapy during the study, which was mainly attributable to insufficient glucose modulation. Improvements in quality of life and treatment satisfaction were found for both types of insulin. This observational study provides evidence from a real-life setting that BOT with insulin glargine provides slightly greater reductions in weight, FBG and HbA1c levels, with a lower risk of hypoglycaemia than patients receiving NPH. This conclusion indicates that insulin glargine may be preferable to NPH insulin for BOT.

Insulin glargine versus insulin degludec in patients failing on oral therapy in type 2 diabetes: A retrospective real world comparative data from India

ObjectiveTo compare the changes in various glycemic parameters in insulin-naïve type 2 diabetes mellitus (DM) patients who were initiated on insulin glargine or insulin degludec in a real world setting. MethodsRetrospective data were analyzed in consecutive type 2 DM patients in a real world setting, who failed oral therapy (at least 2 oral anti-diabetic drugs) and were initiated with either insulin glargine or insulin degludec. The parameters assessed were the changes in HbA1c, fasting plasma glucose, body weight, dose of Insulin and the total number of patient reported hypoglycemic episodes up to 6 months after initiation. ResultAt baseline, insulin glargine and insulin degludec groups were similar in terms of gender, age, weight, HbA1c and duration of diabetes. After 6 months follow up the change in HbA1c (−1.09 versus −1.45 P=0.124), change in FPG (−72.81mg/dl [−4mmol/L] versus −75.88mg/dl [−4.2mmol/L] P=0.755), and the change in body weight (+1.65 versus +0.85 P=0.082) were similar in glargine and degludec groups, respectively. Patients in insulin degludec group experienced significantly lesser patient reported hypoglycemic episodes (12 versus 40) and required significantly lesser dose (25.68Units versus 18.61Units per day; P=0.002) compared to insulin glargine. 41% of the patients reached HbA1C target of ≤7% with insulin glargine compared to 69% with insulin degludec within the specified time period. ConclusionResults from this real world analysis suggest that among type 2 DM patients who were initiated on insulin degludec as compared to insulin glargine may be associated with significantly lesser patient reported hypoglycemic episodes and lesser dose of insulin while achieving similar glycemic control. This study is however limited by the retrospective nature of the data collection.

Efficacy and safety of liraglutide compared with insulin glargine in patients with type 2 diabetes mellitus inadequately controlled with metformin

Objective To observe the effect and safety of the human glucagon-like peptide-1 analogue,liraglutide,versus insulin glargine in patients with type 2 diabetes mellitus inadequately controlled with metformin alone.Method Ninty patients with type 2 diabetes mellitus(aged 18-79 years,HbA1C 7.5％-10.0％,body mass index＜40 kg/m2) who had inadequate glycaemic control on metformin were allocated for the research with an open,randomized,parallel controlled clinical research method.The patients kept the original dose of metformin unchanged and were randomly assigned to the liraglutide group or the insulin glargine group according to a proportion of 1 ∶ 1.Liraglutide group started with a dose of 0.6 mg subcutaneous injection qd,changed to 1.2 mg subcutaneous injection qd after one week and kept unchanged until the end of the research.Insulin glargine group started with a dose of 0.1-0.2 U/kg according to the fingertips peripheral blood glucose level before breakfast on the continuous 3 d before every follow-up.At the baseline,after 4 weeks,12 weeks,20 weeks,and 26 weeks of treatment,HbA1C,blood glucose,lipids weight,blood pressure were arranged to measured.86 patients finally completed the study.Results Mean HbA1C and the success rate of HbA1C ＜7％ were similar between liraglutide group and insulin glargine group [(7.06 ± 0.87) ％ vs (7.25 ± 1.20) ％,47.73 ％ vs 45.23 ％,P＞0.05],while the percentage of subjects reaching the composite endpoint of HbA1C＜7％ with no hypoglycemia and no weight gain was significantly higher in liraglutide group than insulin group(P＜0.05) ; Fasting plasma glucose decreased more markedly in insulin glargine group,2 h postprandial plasma glucose was decreased more markedly in liraglutide group(P＜0.05 or P＜0.01).Liraglutide significantly reduced mean body weight by (3.21 ± 1.18) kg,waist circumference by (3.82 ± 1.21) cm,and body mass index by (1.95 ± 0.61) kg/m2 (P＜0.01 or P＜0.05),while in the insulin glargine group there sere rise of respective figure of(2.86 ± 0.43) kg,(1.52 ± 0.56) cm,and (0.61 ± 0.25) kg/m2 (P＜0.05),systolic blood pressure and serum triglyceride declined.There was no serious adverse affect in both groups,the incidence of mild hypoglycemia was significantly less in liraglutide group and has a statistically significant difference (4.55％ vs 21.43％,P＜0.05).Conclusions Liraglutide showed a good effect on reducing weight,systolic blood pressure,blood lipid and in addition to blood glucose control which is comparable to insulin glargine.What is more,liraglutide had good safety and tolerability,which can be regarded as a good choice for patients with type 2 diabetes mellitus inadequately controlled with metformin alone. Key words: Diabetes mellitus, type 2 ; Liraglutide ; Glucagon-like peptide-1 ; Insulin glargine

Dynamic risk factors associated with non-severe hypoglycemia in patients treated with insulin glargine or exenatide once weekly.

Glycemic control in patients with type 2 diabetes is a dynamic process, and changes in risk factors affecting the incidence of hypoglycemia are not well understood. This study explored the association of longitudinal interactive effects of clinical risk factors and concomitant medications on hypoglycemia risk in patients treated with insulin glargine (IG) or exenatide once weekly (EQW). Pooled patient-level 52-week longitudinal data of treatment with EQW (n = 541) or IG (n = 223) from three controlled trials were analyzed. Proportions of patients with at least one episode of hypoglycemia in the EQW and IG groups were 23% and 54%, respectively. Compared with patients with HbA1c ≥7% (53 mmol/mol) over time, patients with HbA1c <7% had significantly higher hypoglycemia risk in both groups (95% confidence intervals [CI] of odds ratios [OR]: EQW-1.21, 2.81; IG- 6.26, 9.84). The patterns of interaction effect of changing body mass index (BMI) and HbA1c on hypoglycemia risk differed in the two treatment groups: patients with with BMI >35 kg/m(2) had a 119% increased hypoglycemia risk in the EQW group, but a 57% reduced risk in the IG group. Sulfonylurea-treated patients in the EQW and IG groups had 4.7- and 3-fold additional hypoglycemia risk, respectively, versus non-sulfonylurea-treated patients. This study revealed differential effects of tight glycemic control and itsinteraction with treatment-induced changes in BMI on hypoglycemia risk its interaction in patients treated with EQW and IG. The residual adverse effect of sulfonylurea was higher in EQW-treated patients.

Optimizing clinical outcomes resulting from glucose‐lowering therapies in type 2 diabetes: increased confidence about the DPP‐4 inhibitors and continued concerns regarding sulphonylureas and exogenous insulin

Optimizing clinical outcomes resulting from glucose‐lowering therapies in type 2 diabetes: increased confidence about the <scp>DPP</scp>‐4 inhibitors and continued concerns regarding sulphonylureas and exogenous insulin

Effects of basal insulin glargine and omega-3 fatty acid on cognitive decline and probable cognitive impairment in people with dysglycaemia: a substudy of the ORIGIN trial

Diabetes and non-diabetic dysglycaemia are risk factors for accelerated cognitive decline. In this planned substudy of the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial, we assessed whether normalising glucose with insulin glargine or administering omega-3 fatty acids in this population may slow this process or affect the development of cognitive impairment. The ORIGIN trial recruited participants older than 50 years with dysglycaemia who were taking either no or one oral glucose-lowering drug, who had additional risk factors for cardiovascular events, whose HbA1c was less than 9%, and who were not taking insulin. Participants were recruited from 573 sites in 40 countries. Participants were randomly assigned to either titrated basal insulin glargine targeting a fasting plasma glucose concentration of 5.3 mmol/L or lower or standard care and to either omega-3 fatty acid (1 g) or placebo by a factorial design. Outcome adjudicators and data analysts were masked to treatment allocation. Cognitive function was assessed by the Mini-Mental State Examination (MMS) and Digit Symbol Substitution (DSS). The effect of insulin glargine or omega-3 fatty * acid on cognitive function over time, the annualised change in test scores, and the development of probable cognitive impairment were measured. All analyses were restricted to those participants who had a cognitive measurement at both baseline and at least one follow-up visit. The ORIGIN trial is registered with ClinicalTrials.gov, NCT00069784. Participants were randomly assigned between Sept 1, 2003, and Dec 15, 2005. MMSE and DSS were assessed in 11,685 and 3392 ORIGIN participants (mean age 63.4 years [SD 7.7]), who were followed up for a median of 6.2 years (IQR 5.8-6.7). There was no difference in the rate of change of cognitive test scores between the insulin glargine and standard care groups (for the MMSE 0.0046, 95% CI -0.0132 to 0.0224, p=0.39; and for the DSS -0.0362, -0.2180 to 0.1455, p=0.34) or between the omega-3 fatty acid and placebo groups (for the MMSE 0.0013, 95% CI -0.0165 to 0.0191, p=0.21; and for the DSS -0.0605, -0.2422 to 0.1212, p=0.72). Similarly, the incidence of probable cognitive impairment did not differ between the insulin glargine and standard care groups (p=0.065) or the omega-3 fatty acid and placebo groups (p=0.070). In a subgroup analysis, allocation to insulin glargine versus standard care seemed to reduce the decline in the MMSE (but not the DSS) in participants with dysglycaemia but without evidence of diabetes (pinteraction=0.024). In this relatively young cohort of people with dysglycaemia, insulin mediated normoglycaemia and omega-3 fatty acid for over 6 years had a neutral effect on the rate of cognitive decline and on incident cognitive impairment. Future studies should assess the effect of these interventions in an older cohort or the effect of other glucometabolic interventions on cognitive decline. Sanofi.

Basal insulin glargine and microvascular outcomes in dysglycaemic individuals: results of the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial.

As glycaemia and the incidence of microvascular diabetes complications follow a log-linear relationship, it becomes increasingly difficult to demonstrate a microvascular benefit of glucose-lowering when the HbA1c level is close to normal. The Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial randomised 12,537 people with diabetes, impaired glucose tolerance or impaired fasting glucose to receive standard glycaemic care or standard care with the addition of basal insulin glargine (A21Gly,B31Arg,B32Arg human insulin), targeting a fasting plasma glucose level ≤5.3mmol/l. Microvascular outcomes during a median follow-up of 6.2years were examined in participants whose baseline HbA1c was above or below the median of 6.4% (46.4mmol/mol). Allocation to the insulin glargine group reduced the incidence of the primary microvascular composite outcome of kidney and eye disease in participants whose baseline HbA1c level was ≥6.4% (46.4mmol/mol; HR 0.90 [95% CI 0.81, 0.99]) but not in participants with a lower baseline HbA1c (HR 1.07 [95% CI 0.95, 1.20]; p value for interaction 0.031). In people whose baseline HbA1c level was ≥6.4% (46.4mmol/mol), the median post-randomisation change in HbA1c was -0.65% (interquartile range -0.16, -0.91%) after allocation to insulin glargine and -0.33% (-0.83, 0.13%) after allocation to standard care (median HbA1c difference 0.33%; p < 0.0001). A smaller median difference of 0.22% was noted in people whose baseline HbA1c was <6.4% (p < 0.0001). In patients with dysglycaemia, intervention targeting normal fasting glucose levels reduced HbA1c and attenuated the risk of microvascular outcomes in participants with a baseline HbA1c level ≥6.4% (46.4mmol/mol). A neutral effect was seen in those with a lower baseline HbA1c level. ClinicalTrials.gov NCT00069784.

Insulin glargine effectively achieves glycemic control and improves insulin resistance in patients with early type 2 diabetes that exhibit a high risk for cardiovascular disease.

In the present study, the clinical efficacy and safety of administering insulin glargine to early type 2 diabetes (T2D) mellitus patients with a high risk for cardiovascular disease were assessed. A total of 42 early T2D patients at a high risk for cardiovascular disease were randomly divided into an insulin-glargine group and a standard-care group. The patients in the insulin-glargine group received oral antidiabetic agents plus glargine once a day via a subcutaneous injection. The patients in the standard-care group were administered oral antidiabetic agents according to the diabetic treatment guidelines. The median follow-up period was 6.4 years. Comparisons were made between the two groups with regard to levels of plasma glucose, glycosylated hemoglobin (HbA1c) and plasma lipids, the homeostasis model assessment-insulin secretion index (HOMA-β) and HOMA-insulin resistance index (HOMA-IR), as well as the incidence of hypoglycemia, adverse cardiovascular events and body mass index (BMI). The fasting plasma glucose level in the insulin-glargine group was significantly lower than that observed in the standard-care group. However, the levels of 2-h postprandial glucose, HbA1c and plasma lipids, as well as the BMI, were similar when comparing the two groups. Although the level of the HOMA-β did not differ between the two groups, the level of HOMA-IR in the insulin-glargine group was significantly lower than that observed in the standard-care group. During the follow-up period, the incidence of hypoglycemia in the insulin-glargine group was significantly higher when compared with the standard-care group, however, no significant difference in the incidence of adverse cardiovascular events was observed. Therefore, the results of the present study indicated that insulin glargine may effectively achieve glycemic control and improve insulin resistance without increasing the risk for cardiovascular events in early T2D patients that were considered to be at a high risk for cardiovascular disease.

Observational Study of Kidney Function and Albuminuria in Patients With Type 2 Diabetes Treated With Exenatide BID Versus Insulin Glargine

Kidney disease is common among patients with type 2 diabetes (T2DM). Treatment of diabetes seeks to minimize negative kidney impact. To assess the changes in kidney function and incidence of albuminuria in patients with T2DM treated for 1 year with exenatide twice daily (BID) or insulin glargine. Retrospective analyses were performed using an electronic medical record database. Patients inititating treatment with either exenatide BID or insulin glargine between November 2006, and April 2009 comprised the study cohort. The 2 groups were 1:1 propensity score matched on baseline variables yielding 2683 pairs. Measures of kidney function included estimated glomerular filtration rate (eGFR,) and urinary albumin/creatinine ratio (UACR). Mean baseline eGFR was identical between the groups (79 ± 23 mL/min/1.73 m(2)). At 1-year follow-up, there was no significant difference in mean eGFR between the groups (78 mL/min/1.73 m(2) for exenatide BID vs 80 mL/min/1.73 m(2) for insulin glargine; P = .39). Despite matching of multiple characteristics, mean baseline UACR was lower in the exenatide BID group (mean = 34 ± 71 mg/g) compared with the insulin glargine group (183 ± 509 mg/g; P = .03). At follow-up, exenatide BID patients had a mean increase in UACR of 104 mg/g, insulin glargine patients had a decrease of 47 mg/g, but the difference was not significant (P = .19). There were no significant differences in change in kidney function or albuminuria at 1 year in patients treated with exenatide BID compared with insulin glargine as administered in routine practice.

The effect of glargine versus glimepiride on pancreatic β-cell function in patients with type 2 diabetes uncontrolled on metformin monotherapy: open-label, randomized, controlled study

The aim of present study is to assess whether if basal insulin, glargine, could improve insulin secretory function of β-cells compared with glimepiride when metformin alone was failed. This was an open-label and multi-center study for 52 weeks in Korean patients with uncontrolled type 2 diabetes by metformin monotherapy. Subjects were randomized to glargine or glimepiride groups (n = 38 vs. 36, respectively). The primary endpoint was to compare changes in c-peptide via glucagon test after 48 weeks. Glycemic efficacy and safety endpoints (glycated hemoglobin (HbA1c), HOMA-B, fasting plasma glucose (FPG), lipid profiles, and hypoglycemic events) were also checked. The mean disease duration of all subjects was 88.2 months. Changes in C-peptide was no significant different between groups (P = 0.73), even though insulin secretion was not worsened in both groups at the endpoint. Glargine was not superior to glimepiride in other β-cell function indexes such as HOMA-B (P = 0.28). HbA1c and FPG reduced significantly in each groups but not different between two groups. Although, severe hypoglycemia did not occur, symptomatic hypoglycemia was more frequent in glimepiride group (P = 0.01). Insulin glargine was as effective as glimepiride in controlling hyperglycemia and maintaining β-cell function in Korean patients with type 2 diabetes during 48 weeks study period, after failure of metformin monotherapy. Hypoglycemic profile was favorable in the insulin glargine group and less weight gain was observed in the glimepiride group. Our results suggest that glargine and glimepiride can be considered after failure of metformin monotherapy.

Switching from basal or basal-bolus insulin to biphasic insulin aspart 30: Results from the Indian cohort of the A1 chieve study.

Aim:To determine the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) therapy in the Indian patients with type 2 diabetes previously on basal or basal-bolus insulin therapies.Materials and Methods:Patients switching from insulin glargine, neutral protamine Hagedorn (NPH) insulin, or basal-bolus insulin to BIAsp 30 in the Indian cohort of the A1 chieve study were included. Safety and efficacy of treatment was evaluated over 24 weeks.Results:A total of 422 patients (pre-study basal-bolus insulin, 49; NPH insulin, 157; insulin glargine, 216) switched to BIAsp 30. Pre-study insulin doses were 0.61 ± 0.26 U/kg, 0.34 ± 0.2 U/kg and 0.40 ± 0.21 U/kg and the mean week 24 BIAsp 30 doses were 0.50 ± 0.21 U/kg, 0.35 ± 0.15 U/kg and 0.42 ± 0.16 U/kg in the prior basal-bolus insulin, NPH insulin and insulin glargine groups, respectively. No serious adverse drug reactions, major or nocturnal hypoglycemia were reported. The proportion of patients experiencing overall hypoglycemia was significantly lower from baseline (5.6%) to week 24 (1.0%) in the pre-study insulin-glargine group and appeared to be lower in pre-study NPH insulin and basal-bolus insulin groups. Glycemic control improved significantly from baseline week 24 in the pre-study NPH insulin and insulin-glargine groups (P < 0.001), while it appeared to improve in the pre-study basal-bolus group. Quality of life was positively impacted after 24 weeks in all 3 groups.Conclusion:The switch from basal or basal-bolus insulin to BIAsp 30 was safe, well tolerated and improved the glycemic control in this Indian cohort.