(Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus.
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SUBMITTER: Semlitsch T
PROVIDER: S-EPMC8095010 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Abstract This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of ultra?long acting insulin compared with long?acting insulin in patients with T1DM.
| S-EPMC6513582 | biostudies-literature
Project description:IntroductionStrict glucose control using multiple doses of insulin is the standard treatment for type 1 diabetes mellitus (T1DM), but increased risk of hypoglycemia is a frequent drawback. Regular insulin in multiple doses is important for achieving strict glycemic control for T1DM, but short-acting insulin analogues may be better in reducing hypoglycemia and postprandial glucose levels.ObjectiveWe conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effects of short-acting insulin analogues vs regular human insulin on hypoglycemia and postprandial glucose in patients with T1DM.MethodsSearches were run on the electronic databases MEDLINE, Cochrane-CENTRAL, EMBASE, ClinicalTrials.gov, LILACS, and DARE for RCTs published until August 2017. To be included in the study, the RCTs had to cover a minimum period of 4 weeks and had to assess the effects of short-acting insulin analogues vs regular human insulin on hypoglycemia and postprandial glucose levels in patients with T1DM. Two independent reviewers extracted the data and assessed the quality of the selected studies. The primary outcomes analyzed were hypoglycemia (total episodes, nocturnal hypoglycemia, and severe hypoglycemia) and postprandial glucose (at all times, after breakfast, after lunch, and after dinner). Glycated hemoglobin (HbA1c) levels and quality of life were considered secondary outcomes. The risk of bias of each RCT was assessed using the Cochrane Collaboration Risk of Bias table, while the quality of evidence for each outcome was assessed using the GRADEpro software. The pooled mean difference in the number of hypoglycemic episodes and postprandial glucose between short-acting insulin analogues vs. regular human insulin was calculated using the random-effects model.ResultsOf the 2897 articles retrieved, 22 (6235 patients) were included. Short-acting insulin analogues were associated with a decrease in total hypoglycemic episodes (risk rate 0.93, 95% CI 0.87-0.99; 6235 patients; I2?=?81%), nocturnal hypoglycemia (risk rate 0.55, 95% CI 0.40-0.76, 1995 patients, I2?=?84%), and severe hypoglycemia (risk rate 0.68, 95% CI 0.60-0.77; 5945 patients, I2?=?0%); and with lower postprandial glucose levels (mean difference/MD -?19.44 mg/dL; 95% CI -?21.49 to -?17.39; 5031 patients, I2?=?69%) and lower HbA1c (MD -?0,13%; IC 95% -?0.16 to -?0.10; 5204 patients; I2?=?73%) levels.ConclusionsShort-acting insulin analogues are superior to regular human insulin in T1DM patients for the following outcomes: total hypoglycemic episodes, nocturnal hypoglycemia, severe hypoglycemia, postprandial glucose, and HbA1c.
| S-EPMC6317184 | biostudies-literature
Project description:IntroductionThe purpose of this study was to compare insulin degludec with insulin glargine in terms of efficacy and safety in patients with type 2 diabetes.MethodsWe systematically searched PubMed, Embase, Web of Science, and Cochrane Library databases for randomized controlled trials published prior to 13 August 2018 (no language restrictions) which compared insulin degludec with insulin glargine. Our main endpoints were glycemic control, hypoglycemic event, weight gain, and serious adverse events (SAEs). We assessed pooled data using random-effects models.ResultsA total of 15 studies that included 9619 patients in the insulin degludec arm of the studies and 7075 patients in the insulin glargine arm were identified and subsequently assessed. Our analysis showed that compared with insulin glargine, insulin degludec yielded an improved mean reduction in fasting plasma glucose (FPG) (weighted mean difference [WMD] - 5.20 mg/dL, 95% confidence interval [CI] - 7.34, - 3.07, P < 0.00001) and a lower ratio of participants experiencing ≥ 1 severe hypoglycemic event (relative risk [RR] 0.68, 95% CI 0.50, 0.93, P = 0.01) and nocturnal hypoglycemia (RR 0.81, 95% CI 0.75, 0.88, P < 0.0001); however, in the insulin degludec group there was a lower ratio of participants with glycated hemoglobin (HbA1c) of ≤ 7.0% (RR 0.92, 95% CI 0.86, 0.98, P = 0.01). There was no statistically significant difference between the two treatment groups for HbA1c reduction (WMD 0.03, 95% CI - 0.00, 0.07, P = 0.08), body weight gain (WMD 0.12, 95% CI - 0.19, 0.43, P = 0.46), and proportion of participants with SAEs (RR 0.97, 95% CI 0.92, 1.02, P = 0.20).ConclusionsInsulin degludec and insulin glargine provide similar glycemic control, but insulin degludec also lowers the risk of hypoglycemia. Consequently, insulin degludec may be an alternative treatment for the management of patients with type 2 diabetes who are prone to hypoglycemia with insulin glargine.
| S-EPMC6531575 | biostudies-literature
Project description:We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM).Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/ Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system.BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C.Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM.ClinicalTrials.gov NCT02075567 http://www.clinicaltrials.gov/ct2/show/NCT02075567.
| S-EPMC4552855 | biostudies-literature
Project description:AimsThis study assessed the cost-effectiveness of long-acting insulin analogues (LAIAs) vs intermediate/long-acting human insulin (ILAHI) for patients with type 1 diabetes (T1D) in real-world clinical practice.MethodsIndividual-level analyses were conducted within a longitudinal population-based cohort of 540 propensity score-matched T1D patients (LAIAs, n = 270; ILAHI, n = 270) with over 10 years of follow-up using Taiwan's National Health Insurance Research Database, 2004-2013, from third-party payer and healthcare sector perspectives. The study outcomes included the number needed to treat (NNT) to prevent one case of clinical events (eg, hypoglycaemia, diabetes-related complications), medical costs, and cost per case of events prevented. Cost estimates are presented in 2013 British pounds (GBP, £).ResultsThe NNTs using LAIAs vs ILAHI to avoid one case of hypoglycaemia requiring medical assistance, outpatient hypoglycaemia and any diabetes-related complications were 12, 9 and 10 for mean follow-up periods of 5.84, 6.02 and 3.62 years, respectively. From third-party payer and healthcare sector perspectives, using LAIAs instead of ILAHI saved GBP6924-GBP7116 per case of hypoglycaemia requiring medical assistance prevented, GBP5346-GBP5508 per case of outpatient hypoglycaemia prevented, and GBP3570-GBP3680 per case of any diabetes-related complications prevented. Sensitivity analyses considering sampling uncertainty showed that using LAIAs over ILAHI yields at least a 76% probability of cost-saving for avoiding one case of hypoglycaemia requiring medical assistance, outpatient hypoglycaemia or any diabetes-related complications.ConclusionsThis real-world evidence reveals that compared with ILAHI, the greater pharmaceutical costs associated with LAIAs for patients with T1D could be substantially offset by savings from averted hypoglycaemia or diabetes-related complications.
| S-EPMC7163379 | biostudies-literature
Project description:Management of diabetes in elderly subjects is complex and careful management of glucose levels is of particular importance in this population because of an increased risk of diabetes-related complications and hypoglycaemia.The aim of this study was to evaluate the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg), a basal insulin with an ultra-long duration of action, in elderly subjects with type 1 diabetes compared with younger adults.This trial was a randomised, double-blind, two-period, crossover trial conducted in a single centre and included both inpatient and outpatient periods. Subjects were men and women aged 18-35 years inclusive (younger adult group) or ?65 years (elderly group) with type 1 diabetes who received IDeg (0.4 U/kg) via subcutaneous injection in the thigh once-daily for six days. Following 6-day dosing, a 26-hour euglycaemic glucose clamp procedure was conducted to evaluate the steady-state pharmacodynamic effects of IDeg. Blood samples were taken for pharmacokinetic analysis up to 120 h post-dose. Pharmacokinetic endpoints included the total exposure of IDeg, ie the area under the IDeg serum concentration curve during one dosing interval at steady state (AUC(IDeg,?,SS)) (? = 0-24 h, equal to one dosing interval) and the maximum IDeg serum concentration at steady state (C(max,IDeg,SS)). Pharmacodynamic endpoints included the total glucose-lowering effect of IDeg, ie the area under the glucose infusion rate (GIR) curve at steady state (AUC(GIR,?,SS)), and the maximum GIR at steady state (GIR(max,IDeg,SS)).Total exposure (AUC(IDeg,?,SS)) and maximum concentration (C(max,IDeg,SS)) of IDeg were comparable between elderly subjects and younger adults. Estimated mean age group ratios (elderly/younger adult) for AUC(IDeg,?,SS) and C(max,IDeg,SS) and corresponding two-sided 95 % confidence intervals (CIs) were 1.04 (95 % CI 0.73-1.47) and 1.02 (95 % CI 0.74-1.39), respectively. Mean AUC(IDeg,0-12h,SS)/AUC(IDeg,?,SS) was 53 % in both younger adult and elderly subjects, showing that in both age groups IDeg exposure was evenly distributed across the first and second 12 h of the 24-hour dosing interval. No statistically significant differences were observed between younger adult and elderly subjects with regard to AUC(GIR,?,SS) (the primary endpoint of this study) and GIR(max,IDeg,SS). Estimated mean age group ratios (elderly/younger adult) for AUC(GIR,?,SS) and GIR(max,IDeg,SS) and corresponding two-sided 95 % CIs were 0.78 (95 % CI 0.47-1.31) and 0.80 (95 % CI 0.54-1.17), respectively. Duration of action was beyond the clamp duration of 26 h in all subjects.The exposure of IDeg at steady state during once-daily dosing was similar in younger adult and elderly subjects. The glucose-lowering effect of IDeg was numerically lower in elderly subjects compared with younger adults, but no significant differences were observed between age groups. The ultra-long pharmacokinetic and pharmacodynamic properties of IDeg observed in younger adults were preserved in elderly subjects with type 1 diabetes. Clinical trials.gov number: NCT00964418.
| S-EPMC3880476 | biostudies-literature
Project description:We investigate whether lower weight gain with insulin detemir is due to a decrease in energy intake or an increase in energy output and whether any change in energy balance is accompanied by changes in hormones, lipid metabolism and muscle gene expression.
2018-04-20 | GSE37785 | GEO
Project description:BACKGROUND: Insulin analogues may be associated with fewer episodes of hypoglycemia than conventional insulins. However, they are costly alternatives. We compared the cost-effectiveness of insulin analogues and conventional insulins used to treat type 1 and type 2 diabetes mellitus in adults. METHODS: We conducted a cost-effectiveness evaluation of insulin analogues versus conventional insulins using the Center for Outcomes Research Diabetes Model. We compared rapid-acting analogues (insulin aspart and insulin lispro) with regular human insulin, and long-acting analogues (insulin glargine and insulin detemir) with neutral protamine Hagedorn insulin. We derived clinical information for the comparisons from meta-analyses of randomized controlled trials. We obtained cost and utility estimates from published sources. We performed sensitivity analyses to test the robustness of our results. RESULTS: For type 1 diabetes, insulin aspart was more effective and less costly than regular human insulin. Insulin lispro was associated with an incremental cost of Can$28,996 per quality-adjusted life-year. The incremental cost per quality-adjusted life-year was Can$87,932 for insulin glargine and Can$387,729 for insulin detemir, compared with neutral protamine Hagedorn insulin. For type 2 diabetes, insulin aspart was associated with an incremental cost of Can$22,488 per quality-adjusted life-year compared with regular human insulin. For insulin lispro, the incremental cost was Can$130,865. Compared with neutral protamine Hagedorn insulin, insulin detemir was less effective and more costly. Insulin glargine was associated with an incremental cost of Can$642,994 per quality-adjusted life-year. The model was sensitive to changes in the effect size of hemoglobin A(1c) and to decrements applied to utility scores when fear of hypoglycemia was included as a factor. INTERPRETATION: The cost-effectiveness of insulin analogues depends on the type of insulin analogue and whether the patient receiving the treatment has type 1 or type 2 diabetes. With the exception of rapid-acting insulin analogues in type 1 diabetes, routine use of insulin analogues, especially long-acting analogues in type 2 diabetes, is unlikely to represent an efficient use of finite health care resources.
| S-EPMC2638053 | biostudies-other
Project description: Not available
| S-EPMC7048883 | biostudies-literature
Project description:BackgroundIncreasing availability of competing biosimilar alternatives makes it challenging to make treatment decisions. The purpose of this review is to evaluate the comparative efficacy and safety of ultra-long-/long-/intermediate-acting insulin products and biosimilar insulin compared to human/animal insulin in adults with type 1 diabetes mellitus (T1DM).MethodsMEDLINE, EMBASE, CENTRAL, and grey literature were searched from inception to March 27, 2019. Randomized controlled trials (RCTs), quasi-experimental studies, and cohort studies of adults with T1DM receiving ultra-long-/long-/intermediate-acting insulin, compared to each other, as well as biosimilar insulin compared to human/animal insulin were eligible for inclusion. Two reviewers independently screened studies, abstracted data, and appraised risk-of-bias. Pairwise meta-analyses and network meta-analyses (NMA) were conducted. Summary effect measures were mean differences (MD) and odds ratios (OR).ResultsWe included 65 unique studies examining 14,200 patients with T1DM. Both ultra-long-acting and long-acting insulin were superior to intermediate-acting insulin in reducing A1c, FPG, weight gain, and the incidence of major, serious, or nocturnal hypoglycemia. For fasting blood glucose, long-acting once a day (od) was superior to long-acting twice a day (bid) (MD - 0.44, 95% CI: - 0.81 to - 0.06) and ultra-long-acting od was superior to long-acting bid (MD - 0.73, 95% CI - 1.36 to - 0.11). For weight change, long-acting od was inferior to long-acting bid (MD 0.58, 95% CI: 0.05 to 1.10) and long-acting bid was superior to long-action biosimilar od (MD - 0.90, 95% CI: - 1.67 to - 0.12).ConclusionsOur results can be used to tailor insulin treatment according to the desired results of patients and clinicians and inform strategies to establish a competitive clinical market, address systemic barriers, expand the pool of potential suppliers, and favor insulin price reduction.Prospero registrationCRD42017077051.
| S-EPMC8342652 | biostudies-literature