Premixed vs basal-bolus insulin regimen in Type 2 diabetes: comparison of clinical outcomes from randomized controlled trials and real-world data.

AIM: To evaluate the concordance between data derived from randomized controlled trial (RCT) and real-world estimates of HbA1c and weight change after 24 weeks of initiation of a basal-bolus compared with a premixed insulin regimen in people with Type 2 diabetes. METHODS: Data eight RCTs were pooled after a systematic review of studies examining basal-bolus (n = 1893) or premixed (n = 1517) regimens. Real-world data were extracted from the UK primary care dataset for people on basal-bolus (n = 7483) or premixed insulin regimens (n=10 744). The mean differences between HbA1c and weight from baseline were calculated using t-tests, while analysis of variance was used to compare the two treatment regimens. Linear regression analyses were used to determine the predictors of this change. RESULTS: Both insulin regimens were associated with HbA1c reductions (real-world data -0.28%; RCT data, -1.4%) and weight gain (real-world data, +0.27 kg; RCT data, +2.96 kg) but there were no significant differences between basal-bolus and premixed insulin. Discordances in the pattern of treatment response were observed, however, between real-world and RCT data for both insulin regimens. For any given baseline HbA1c concentration, the change in HbA1c in the RCTs was greater than in real-world conditions and for those with baseline weight above ~60 kg, RCT data showed overall weight gain in contrast to slight weight loss in the real-world population. Lastly, for both randomized controlled trial and real-world populations, while greater baseline weight was associated with reduced response to treatment, the association was much steeper in the RCT than in the real-world population. In addition, greater baseline weight was associated with greater weight reductions in both premixed insulin and basal-bolus insulin regimens, although to a lesser extent with the latter. CONCLUSION: These results highlight specific discrepancies in the HbA1c reduction and weight change in insulin regimen between real world versus RCT populations; with greater reduction in HbA1c and greater increase in weight observed in the RCT population than in the real-world population. Also, the basal-bolus regimens in both real-world and RCT populations showed greater reduction in HbA1c compared to the premix regimen (though more marked in RCTs), while the premix regimen showed greater increase in weight in real-world, as against basal-bolus in the RCT population.

Comparison of cardiovascular and metabolic outcomes in people with type 2 diabetes on insulin versus non-insulin glucose-lowering therapies (GLTs): A systematic review and meta-analysis of clinical trials.

OBJECTIVES: To compare the cardiovascular and metabolic outcomes of Insulin versus non-insulin glucose lowering therapy (GLT). METHODS: We included randomised control trials (RCTs) which randomised patients aged >18years with Type 2 Diabetes (T2D) to insulin vs non-insulin GLT. We used risk ratios (RR), risk difference (RD) and odds ratios (OR) with 95% confidence interval (95%CI) to analyse the treatment effects of dichotomous outcomes and mean differences (with 95% CI) for continuous outcomes. RESULTS: We included 18 RCTs with 19,300 participants. There was no significant difference in the risk of all-cause mortality and CV events between the groups (RR=1.01; 95%CI: 0.96-1.06; p=0.69). In 16 trials, insulin showed greater efficacy in glycaemic control (mean diff=-0.20; 95%CI: -0.28 to -0.11) but the proportion achieving HbA1c level of either ⩽7.0% or 7.4% (53 or 57mmol/mol) was similar in both (OR=1.55; 95%CI=0.92-2.62). The non-insulin group had a significant reduction in weight (mean diff=-3.41; 95%CI: -4.50 to -2.32) and an increase in the proportion of adverse events (54.7% vs 45.3%, p=0.044), but the insulin group showed an (RR=1.90; 95%CI: 1.44-2.51) increased risk of hypoglycaemia. CONCLUSION: There was no difference in the risk of all-cause mortality and adverse cardiovascular (CV) events between Insulin and non-insulin GLTs. Insulin was associated with superior reduction in HbA1c; least reduction in weight and higher risk of hypoglycaemia. Both showed similar proportion of patients achieving HbA1c target. Non-insulin GLTs were associated with a higher risk in reported adverse drug events.

Clinical use and efficacy of biphasic insulin lispro 50/50 in people with insulin treated diabetes - a nationwide evaluation of clinical practice.

OBJECTIVES: This study aims to investigate the metabolic effects of biphasic insulin lispro 50/50 in routine clinical practice. A total of 229 patients who were ≥18 years old with diabetes, newly treated with biphasic insulin lispro 50/50, were sourced from six secondary care services in England. METHODS: Detailed clinical parameters were compared at baseline, and 3 and 6 months post-initiation. Responders was defined as those with HbA1c <7.5% (58 mmol/mol) and/or an HbA1c reduction of >1% (11 mmol/mol) at 6 months. RESULTS: HbA1c showed significant reduction: -0.93% (-10 mmol/mol) and -1.2% (-13 mmol/mol) at 3 and 6 months respectively, while no significant change was noted for all the other parameters. When analyzed according to frequencies of injections/day, the greatest reduction was observed with the three times a day regimen (-1.0% [-11.0 mmol/mol] and -1.3% [-14.6 mmol/mol] at 3 and 6 months respectively). HbA1c reduction was greatest in the group who previously received a basal-bolus insulin regimen: (-0.8% [-9.0 mmol/mol] and -1.5% [-16.2 mmol/mol] at 3 and 6 months respectively). Reduction in weight was observed at 3 months (-1.8 kg ± 4.3) only for those who were previously on a basal-bolus insulin regimen. Insulin doses increased following conversion to biphasic insulin lispro 50/50, irrespective of the types of insulin used prior to biphasic insulin lispro 50/50, but this was not associated with weight gain. The independent predictors of response to biphasic insulin lispro 50/50 were baseline HbA1c, Caucasian, presence of nephropathy, prior use of basal-bolus insulin and prior use of other premixed combination. CONCLUSION: Biphasic insulin lispro 50/50 is therefore an effective therapeutic option for achieving glycemic control in patients with suboptimal HbA1c levels, especially among those who were previously on a basal-bolus insulin regimen and those who received it three times daily, with a neutral effect on weight parameters. LIMITATIONS: This was a retrospective study of routine clinical practice and is therefore limited by allocation bias and some missing data. Information on rates of hypoglycemia and quality of life are not available.

Biphasic vs basal bolus insulin regimen in Type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

AIM: We aim to evaluate the effects of biphasic insulin compared with a basal bolus insulin regimen on glycaemic control, total daily insulin requirements, risk of hypoglycaemia, weight and quality of life in patients with diabetes mellitus. METHODS: MEDLINE, EMBASE, PubMed and Scopus databases were searched for studies up to November 2013. Interventions that lasted for more than four weeks and were reported in English were considered for the review. Meta-analysis was performed on eligible studies. RESULTS: Fifteen randomized controlled trial studies, involving 4384 patients, were included. Greater HbA1c reductions were seen with basal-bolus compared with biphasic insulin regimens, between-treatment weighted mean difference (WMD) for baseline-to-endpoint changes in HbA1c was -0.2% (95% CI: -0.36 to -0.03) [-2.2 (-3.9, -0.3) mmol/mol]. In non-insulin naïve (n = 8) patients with Type 2 diabetes, HbA1c reduction was greater in the basal bolus group; WMD = -0.22% (95% CI: -0.42 to -0.02) [-2.4 (-4.6, -0.2) mmol/mol], but in insulin naïve patients (n = 5), HbA1c was equivalent between the two regimens; WMD (-0.15% (95% CI: -0.52 to 0.22) [-1.6 (-5.7, 2.4) mmol/mol]. Total daily insulin requirements and weight were increased with both regimens, whereas hypoglycaemia rates were comparable between the two regimens. Greater HbA1c reduction was observed in the basal bolus group compared with the biphasic regimen at the expense of higher daily insulin requirements and weight gain, but with no greater risk of hypoglycaemia. CONCLUSIONS: Biphasic and basal bolus regimens were equally effective in reducing HbA1c in insulin naïve patients with Type 2 diabetes and both regimens are equally effective for initiating insulin in Type 2 diabetes.

Obesity independently predicts responders to biphasic insulin 50/50 (Humalog Mix50 and Insuman Comb 50) following conversion from other insulin regimens: a retrospective cohort study.

AIMS: This study aims to examine the metabolic effects of intensification or initiation of insulin treatment with biphasic insulin 50/50, and determine the predictors of responders or non-responders to biphasic insulin 50/50. METHODS: A cohort of 2183 patients ≥18 years with diabetes, newly treated with biphasic insulin 50/50 between January 2000 and May 2012, were sourced from UK General Practices via The Health Improvement Network (THIN) database. Baseline clinical parameters of 1267 patients with suboptimal glycated hemoglobin (HbA1c) >7.5% (>58 mmol/mol) who had received background insulin regimens for at least 6 months preceding biphasic insulin 50/50 were compared against 12-month outcome data. Responders were defined as those with HbA1c <7.5% (58 mmol/mol) and/or HbA1c reduction of ≥1% (10.9 mmol/mol) at 12 months. Comparative analyses were carried out on subgroups of 237 patients initiating insulin therapy with biphasic insulin 50/50, and between users of the Humalog Mix50 (HM50) versus Insuman Comb 50 (IC50). Associations were examined using t tests and multivariate logistic regression techniques. RESULTS: The overall mean HbA1c reduction at 12 months as a result of intensification and initiation with biphasic insulin 50/50 was 0.5% (5.5 mmol/mol) and 1.6% (17.5 mmol/mol), respectively. Adjusted ORs show obesity (body mass index >30 kg/m(2)), treatment duration for ≥9 months, and baseline HbA1c are independent determinants of responders. In addition, stratified for baseline HbA1c levels, HM50 was associated with better HbA1c outcome compared with IC50. CONCLUSIONS: biphasic insulin 50/50 is effective for achieving glycemic control in suboptimal HbA1c levels, especially among obese patients with insulin-treated diabetes. Stratified for baseline HbA1c, HM50 was associated with improved HbA1c outcome compared with IC50.