Rapid-Acting Insulin Analogues Versus Regular Human Insulin: A Meta-Analysis of Effects on Glycemic Control in Patients with Diabetes.
Ontology highlight
ABSTRACT:
SUBMITTER: Nicolucci A
PROVIDER: S-EPMC7048883 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
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: Not available
| S-EPMC8095010 | biostudies-literature
Project description:IntroductionDiabetic ketoacidosis (DKA) is traditionally managed using intravenous regular insulin infusion (RII) in intensive care unit (ICU)/high dependency unit (HDU). Subcutaneous fast-acting insulin analogues (FAIAs) may help to manage DKA outside ICU/HDU. Furthermore, combining subcutaneous long-acting insulin (LAI) with subcutaneous FAIAs may accelerate ketoacidosis resolution. The latest (2016) Cochrane review was inconclusive regarding subcutaneous FAIAs versus intravenous RII in DKA. It was limited by small sample sizes, unclear risk of bias (RoB) in primary trials and did not examine subcutaneous FAIAs with subcutaneous LAI versus intravenous RII in DKA. We report the protocol for an updated meta-analysis on the safety and benefits of subcutaneous FAIAs with/without subcutaneous LAI versus intravenous RII in DKA.Methods and analysisWe will search Medline, Embase, CINAHL and Cochrane Library, from inception until December 2022, without language restrictions, for randomised trials on subcutaneous FAIAs with/without subcutaneous LAI versus intravenous RII in DKA. We also search ClinicalTrials.gov, ClinicalTrialsRegister.eu and reference lists of included trials. Primary outcomes include all-cause in-hospital mortality, time to DKA resolution, in-hospital DKA recurrence and hospital readmission for DKA post-discharge. Secondary outcomes include resource utilisation and patient satisfaction. Safety outcomes include important complications of DKA and insulin. Reviewers will extract data, assess overall RoB and quality of evidence using Grading of Recommendations, Assessment, Development and Evaluation. We will assess statistical heterogeneity by visually inspecting forest plots and the I2 statistic. We will synthesise data using the random-effects model. Predefined subgroup analyses are: mild versus moderate versus severe DKA; age <20 vs ≥20 years; pregnant versus non-pregnant; infective versus non-infective DKA precipitating cause; subcutaneous FAIAs alone versus subcutaneous FAIAs and subcutaneous LAI; and high versus low overall RoB. We will also perform trial sequential analysis for primary outcomes.Ethics and disseminationEthics board approval is not required. Results will be disseminated through publication in a peer-reviewed journal.Prospero registration numberCRD42022369518.
| S-EPMC9923333 | biostudies-literature
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:BackgroundFaster aspart is insulin aspart (IAsp) in a new formulation, which in continuous subcutaneous insulin infusion (CSII) in subjects with type 1 diabetes has shown a faster onset and offset of glucose-lowering effect than IAsp.MethodsThis double-blind, randomized, crossover active-controlled trial compared 2-h postprandial plasma glucose (PPG) response, following 2 weeks of CSII with faster aspart or IAsp. Primary endpoint: mean change in PPG 2 h after a standardized meal test (ΔPGav,0-2h). Subjects (n = 43) had masked continuous glucose monitoring (CGM) throughout.ResultsFaster aspart provided a statistically significantly greater glucose-lowering effect following the meal versus IAsp: ΔPGav,0-2h: 3.03 mmol/L versus 4.02 mmol/L (54.68 mg/dL vs. 72.52 mg/dL); estimated treatment difference (ETD) [95% CI]: -0.99 mmol/L [-1.95; -0.03] (-17.84 mg/dL [-35.21; -0.46]; P = 0.044). One hour postmeal, PG levels were -1.64 mmol/L (-29.47 mg/dL) lower with faster aspart versus IAsp (P = 0.006). Interstitial glucose (IG) profiles supported these findings; the largest differences were observed at breakfast: 9.08 versus 9.56 mmol/L (163.57 vs. 172.19 mg/dL; ETD [95% CI]: -0.48 mmol/L [-0.97; 0.01]; -8.62 mg/dL [-17.49; 0.24]; P = 0.057). Duration of low IG levels (≤3.9 mmol/L [70 mg/dL] per 24 h) was statistically significantly shorter for faster aspart versus IAsp (2.03 h vs. 2.45 h; ETD [95% CI]: -0.42 [-0.72; -0.11]; P = 0.008). No unexpected safety findings were observed.ConclusionsCSII delivery of faster aspart had a greater glucose-lowering effect than IAsp after a meal test. CGM results recorded throughout all meals supported this finding, with less time spent with low IG levels.
| S-EPMC5248540 | biostudies-literature
Project description:The safety and efficacy of sitagliptin as add-on therapy to glinides, rapid-acting insulin secretagogues, were evaluated for Japanese patients with type 2 diabetes mellitus. This 52-week study consisted of a 12-week double-blind period, followed by a 40-week open-label period. During the double-blind period, patients were randomized to sitagliptin 50 mg q.d. (S/S group) or placebo (P/S group) as add-on therapy to glinide monotherapy. During the open-label period, all patients in both groups were administered sitagliptin 50 mg q.d. (or 100 mg q.d. after up-titration). During the double-blind period, the overall occurrence of adverse experiences (AE) was similar in both treatment groups. The frequency of reported AE of hypoglycemia in both groups was low and not notably different. The nature of clinical AE during the open-label period for both groups was not notably different from that of clinical AE in the sitagliptin group during the double-blind period. The between-group difference in HbA1c least squares (LS) mean of change from baseline (95 % CI) at Week 12 was -1.1 % (-1.3, -0.8) in favor of sitagliptin (P < 0.001). LS mean of reductions from baseline of fasting plasma glucose and 2-h postmeal glucose were significantly greater in the sitagliptin group than in the placebo group: -23.1 mg/dL (-32.2, -13.9) and -51.2 mg/dL (-67.4, -35.0), respectively (both P < 0.001). The changes from baseline in glycemic data in the S/S group remained generally stable throughout the 52-week treatment period.
| S-EPMC6224996 | biostudies-literature
Project description:OBJECTIVE Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump has been available for the past 25 years. CIPII, with its specific pharmacodynamic properties, may be a viable treatment alternative to improve glycemic control in patients with type 1 diabetes for whom other therapies have failed. There have been few studies in which CIPII was compared with subcutaneous insulin treatment for patients with type 1 diabetes with poor glycemic control. RESEARCH DESIGN AND METHODS In an open-label, prospective, crossover, randomized, 16-month study, the effects of CIPII and subcutaneous insulin were compared in 24 patients. The primary outcome measure was the incidence of hypoglycemia. Secondary outcome measures were A1C, and glucose profile, including time in euglycemia, as measured by continuous glucose monitoring. RESULTS The incidence of grade 1 hypoglycemic events was 4.0 +/- 2.6 per week with subcutaneous insulin compared with 3.5 +/- 2.3 per week during CIPII (P = 0.13). The absolute mean difference in A1C with CIPII compared with subcutaneous treatment was -0.76% (95% CI -1.41 to -0.11) (P = 0.03). Baseline time spent in euglycemia was 45.2 +/- 12.6% and increased 10.9% (4.6-17.3) with CIPII compared with subcutaneous treatment (absolute value; P = 0.003). There were no differences in the occurrence rate for severe hypoglycemic events, daily insulin use, or BMI. No pump or catheter malfunction was observed during the study. CONCLUSIONS Although we did not observe a significant reduction in hypoglycemic events, improved glycemic control was achieved with the use of CIPII. We saw a 0.8% decrease in A1C and an 11% increase in the time spent in euglycemia.
| S-EPMC2713651 | biostudies-literature
Project description: Not available
| S-EPMC8094220 | biostudies-literature
Project description:Background and aimsFew studies have evaluated long-term durability of glycemic control in older patients. The aim of this study was to compare durability of glycemic control of twice-daily insulin lispro mix 75/25 (LM75/25; 75 % insulin lispro protamine suspension, 25 % insulin lispro) and once-daily insulin glargine (GL) added to oral antihyperglycemic medications in older patients (≥65 years of age).MethodsPatients were participants in the maintenance phase of the DURABLE trial. During the initiation phase, patients with type 2 diabetes were randomized to LM75/25 or GL. After 6 months, patients with hemoglobin A1c (HbA1c) ≤7.0 % advanced to the 24-month maintenance phase. The primary objective was between-group comparison of duration of maintaining the HbA1c goal in older patients (≥65 years of age). A similar analysis was conducted for older patients achieving HbA1c ≤6.5 % in the initiation phase.ResultsMedian time of maintaining HbA1c goal was longer in LM75/25 versus GL (19.6 versus 15.4 months, p = 0.007) and more LM75/25 patients maintained goal versus GL (49.2 versus 30.4 %; p = 0.003). HbA1c reduction from baseline was greater in LM75/25 versus GL (-1.56 ± 0.10 versus -1.24 ± 0.11 %; p = 0.003). Post-meal glucose was significantly lower in LM75/25 versus GL (158.86 ± 3.42 versus 171.67 ± 4.51 mg/dL; p = 0.017). No differences were observed in overall and severe hypoglycemia. LM75/25 patients had higher daily insulin doses (0.41 ± 0.02 versus 0.32 ± 0.02 units/kg/day; p < 0.001) and more weight gain (5.47 ± 0.49 versus 3.10 ± 0.53 kg; p = 0.001). Similar results were generally obtained in older patients with HbA1c ≤6.5 %.ConclusionsIn our evaluation of older patients from a larger trial, LM75/25 appeared to provide longer durability of glycemic control, as well as a greater number of patients maintaining HbA1c goal versus GL.
| S-EPMC3955127 | biostudies-literature
Project description:ObjectiveClamp studies have shown that the absorption and action of rapid-acting insulin are faster with injection by a jet injector than with administration by conventional pen. To determine whether these pharmacokinetic changes also exist in patients with diabetes and benefit postprandial glucose control, we compared the pharmacologic profiles of insulin administration by jet injection versus conventional insulin pen after a standardized meal in patients with type 1 or type 2 diabetes.Research design and methodsIn a randomized, double-blind, double-dummy crossover study, 12 patients with type 1 diabetes and 12 patients with type 2 diabetes received insulin aspart either by jet injection or by conventional pen, in both cases followed by a standardized meal. Blood was sampled for 6 h for determination of glucose and insulin levels to calculate pharmacologic profiles.ResultsInsulin administration by jet injection resulted in shorter time until peak plasma insulin level (51.3 ± 6.4 vs. 91.9 ± 10.2 min; P = 0.003) and reduced hyperglycemic burden during the first hour (154.3 ± 20.8 vs. 196.3 ± 18.4 mmol · min · L(-1); P = 0.041) compared with conventional administration. Jet injection did not, however, significantly reduce the hyperglycemic burden during the 5-h period thereafter. There was no indication that the jet injector performed differently in patients with type 1 and type 2 diabetes.ConclusionsThe considerably more rapid insulin absorption after administration by jet injector translated to a significant if modest decrease in postprandial hyperglycemia in patients with type 1 and type 2 diabetes. The improved early postprandial glucose control may specifically benefit patients who have difficulty in limiting postprandial glucose excursions.
| S-EPMC3816925 | biostudies-literature