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BMJ Open Feb 2016To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM).
DESIGN
This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO.
OUTCOME MEASURES
Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed.
RESULTS
41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: -0.08; 95% credible interval (CrI): -0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; -0.28 to 0.32), degludec (-0.12; -0.42 to 0.20) and premixed insulin (0.26; -0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; -0.31 to 1.71), NPH (-0.76; -1.75 to 0.21) and degludec (-0.63; -1.63 to 0.35), but significantly lower compared with premixed insulin (-1.83; -2.85 to -0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19 to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings.
CONCLUSIONS
NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to available basal insulin comparators.
Topics: Body Weight; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine
PubMed: 26880669
DOI: 10.1136/bmjopen-2015-009421 -
The American Journal of Managed Care Jul 2018The objective of this literature review was to evaluate the costs associated with the use of long-acting insulin analogues (LAIAs) compared with non-LAIA agents,... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVES
The objective of this literature review was to evaluate the costs associated with the use of long-acting insulin analogues (LAIAs) compared with non-LAIA agents, including human insulin, oral antidiabetic drugs, and other injectable therapies, in the treatment of patients with type 1 diabetes (T1D) or type 2 diabetes (T2D).
STUDY DESIGN
A systematic review of the medical literature (MEDLINE, EMBASE, Cochrane, EconLit) conducted from 2004 to 2016.
METHODS
The review protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria for studies were: patients with T1D and/or T2D, LAIA intervention, and comparators, including oral antidiabetics (OADs) or neutral protamine Hagedorn (NPH). Outcomes of interest were adherence measures; economic outcomes, including total costs, cost savings, and willingness-to-pay; and cost-effectiveness or incremental cost-effectiveness analyses. Real-world costs of individual LAIAs were also evaluated and are often compared against those of other LAIAs in the economic analyses.
RESULTS
We identified and included 117 relevant studies. Patients using LAIAs had higher drug costs than those using OADs and NPH but had neutral or reduced total and diabetes-related costs compared with patients using non-LAIAs. Use of LAIA pen-delivery systems may lead to improved adherence and reduction in costs. Patients receiving insulin glargine demonstrated higher adherence and persistence than patients on insulin detemir. Economic models suggest that LAIAs are more cost-effective than NPH for T1D; for T2D, insulin glargine is more costly than NPH but less so than insulin detemir.
CONCLUSIONS
Despite higher drug costs, the real-world overall medical costs of LAIAs are not significantly different from those of NPH in patients with diabetes. The findings may be helpful for formulary decision making for patients with diabetes in a cost-constrained environment.
Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Costs; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Quality-Adjusted Life Years; United States
PubMed: 30020738
DOI: No ID Found -
Clinical Therapeutics 2007Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which insulin deficiency is one of the core defects. When patients with T2D are... (Comparative Study)
Comparative Study Review
BACKGROUND
Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which insulin deficiency is one of the core defects. When patients with T2D are unable to achieve glycemic goals with diet and oral antihyperglycemic medications, a common starting insulin regimen consists of basal or premixed insulin added to oral antihyperglycemic medications. When glycemic goals are not achieved with the initial insulin regimen, a basal-bolus regimen is necessary.
OBJECTIVE
This article reviews clinical-trial data on the efficacy and safety profile of prandial premixed insulin analogues (insulin aspart and insulin lispro) compared with basal insulin analogues (insulin glargine, insulin detemir, and insulin lispro protamine suspension), with or without a prandial insulin analogue, in the management of T2D.
METHODS
A systematic search of Ovid, MEDLINE, and EMBASE (1995-2007) was performed to identify published randomized controlled trials comparing prandial premixed insulin analogues with basal insulin analogues, with or without prandial insulin, in patients with T2D. The search terms were premixed insulin analogues, premixed insulin, biphasic insulin aspart, insulin aspart 70/30, insulin aspart 50/50, premixed insulin lispro, insulin lispro 75/25, insulin lispro 50/50, glargine, and detemir. Abstracts presented at the 2005 and 2006 meetings of the American Diabetes Association and the European Association for the Study of Diabetes and bibliographies of the identified studies were also reviewed. Predetermined criteria for study inclusion were treatment duration of at least 12 weeks, T2D diagnosed using valid criteria, use of a basal insulin analogue (with or without rapid-acting insulin) as a study comparator, and use of well-accepted end points (eg, glycosylated hemoglobin [HbA1c], hypoglycemia, preprandial and postprandial blood glucose).
RESULTS
Of the identified randomized controlled trials, 3 studies compared premixed insulin analogues containing 70% or 75% basal and 30% or 25% rapid-acting insulin analogue with basal insulin analogues only, and 3 studies evaluated premixed insulin analogues containing 50% basal and 50% rapid-acting insulin analogue with basal insulin analogues only. Use of prandial premixed insulin analogues was associated with better overall and postprandial glycemic control. In the studies that compared twice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA1c ranged from -1.00% to -2.79% and from -0.42% to -2.36%, respectively (P < 0.01). In the studies that compared thrice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA1c ranged from -0.72% to -1.2% and from -0.3% to -0.75%, respectively (P < 0.01). These results were achieved with some increase in overall hypoglycemia, but not in nocturnal or severe hypoglycemia. Doses of the premixed insulin analogues were adjusted during the titration period to achieve glycemic goals.
CONCLUSIONS
The results of this systematic review suggest that regimens consisting of prandial premixed insulin analogues, which provide both basal and prandial insulin coverage, may be used as an initial insulin regimen in patients with T2D to enable better overall, preprandial, and postprandial glycemic control compared with a basal insulin analogue regimen alone. Premixed insulin analogues are an effective option for initiating and intensifying insulin therapy in patients with T2D.
Topics: Diabetes Mellitus, Type 2; Evidence-Based Medicine; Humans; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Randomized Controlled Trials as Topic
PubMed: 18046926
DOI: No ID Found -
Clinical Therapeutics Jun 2007Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which insulin deficiency is one of the core defects. When patients with T2D are... (Review)
Review
BACKGROUND
Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which insulin deficiency is one of the core defects. When patients with T2D are unable to achieve glycemic goals with diet and oral antihyperglycemic medications, a common starting insulin regimen consists of basal or premixed insulin added to oral antihyperglycemic medications. When glycemic goals are not achieved with the initial insulin regimen, a basal-bolus regimen is necessary.
OBJECTIVE
This article reviews clinical-trial data on the efficacy and safety profile of prandial premixed insulin analogues (insulin aspart and insulin lispro) compared with basal insulin analogues (insulin glargine, insulin detemir, and insulin lispro protamine suspension), with or without a prandial insulin analogue, in the management of T2D.
METHODS
A systematic search of Ovid, MEDLINE, and EMBASE (1995-2007) was performed to identify published randomized controlled trials comparing prandial premixed insulin analogues with basal insulin analogues, with or without prandial insulin, in patients with T2D. The search terms were premixed insulin analogues, premixed insulin, biphasic insulin aspart, insulin aspart 70/30, insulin aspart 50/50, premixed insulin lispro, insulin lispro 75/25, insulin lispro 50/50, glargine, and detemir. Abstracts presented at the 2005 and 2006 meetings of the American Diabetes Association and the European Association for the Study of Diabetes and bibliographies of the identified studies were also reviewed. Predetermined criteria for study inclusion were treatment duration of at least 12 weeks, T2D diagnosed using valid criteria, use of a basal insulin analogue (with or without rapid-acting insulin) as a study comparator, and use of well-accepted end points (eg, glycosylated hemoglobin [HbA(1c)], hypoglycemia, preprandial and postprandial blood glucose).
RESULTS
Of the identified randomized controlled trials, 3 studies compared premixed insulin analogues containing 70% or 75% basal and 30% or 25% rapid-acting insulin analogue with basal insulin analogues only, and 3 studies evaluated premixed insulin analogues containing 50% basal and 50% rapid-acting insulin analogue with basal insulin analogues only. Use of prandial premixed insulin analogues was associated with better overall and postprandial glycemic control. In the studies that compared twice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA(1c) ranged from -1.00% to -2.79% and from -0.42% to -2.36%, respectively (P < 0.01). In the studies that compared thrice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA(1c) ranged from -0.72% to -1.2% and from -0.3% to -0.75%, respectively (P < 0.01). These results were achieved with some increase in overall hypoglycemia, but not in nocturnal or severe hypoglycemia. Doses of the premixed insulin analogues were adjusted during the titration period to achieve glycemic goals.
CONCLUSIONS
The results of this systematic review suggest that regimens consisting of prandial premixed insulin analogues, which provide both basal and prandial insulin coverage, may be used as an initial insulin regimen in patients with T2D to enable better overall, preprandial, and postprandial glycemic control compared with a basal insulin analogue regimen alone. Premixed insulin analogues are an effective option for initiating and intensifying insulin therapy in patients with T2D.
Topics: Body Weight; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Evidence-Based Medicine; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Randomized Controlled Trials as Topic
PubMed: 18036388
DOI: 10.1016/j.clinthera.2007.07.003 -
Expert Review of Pharmacoeconomics &... Dec 2011The prevalence of diabetes and cost of associated treatment are steadily increasing, as is the resulting burden on healthcare systems worldwide. Current treatment... (Review)
Review
The prevalence of diabetes and cost of associated treatment are steadily increasing, as is the resulting burden on healthcare systems worldwide. Current treatment recommendations for Type 1 and Type 2 diabetes advise a prominent role for basal insulin. We examined the published health-economic literature pertaining to the basal insulin analog insulin detemir (IDet) to determine whether IDet is a cost-saving and/or cost-effective treatment for suboptimally controlled Type 1 or Type 2 diabetes. A total of 15 modeling studies were assessed, most of which found IDet to be cost effective compared with neutral protamine Hagedorn and as cost effective as insulin glargine. Those that did not find IDet to be cost effective set the disutility of hypoglycemic events to almost zero or assumed a higher dose of IDet with no difference in treatment effect, ignoring the clinical benefits and cost savings associated with IDet in studies demonstrating comparable or superior glycemic control with less hypoglycemia versus other basal insulins. The evidence suggests that IDet is cost effective versus neutral protamine Hagedorn and at least as cost effective as insulin glargine in the treatment of patients with suboptimally controlled Type 1 and Type 2 diabetes.
Topics: Blood Glucose; Cost Savings; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Models, Economic; Quality-Adjusted Life Years; Time Factors; Treatment Outcome
PubMed: 21961796
DOI: 10.1586/erp.11.73 -
The Cochrane Database of Systematic... Apr 2007Despite indications from epidemiological trials that higher blood glucose concentrations are associated with a higher risk for developing micro- and macrovascular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite indications from epidemiological trials that higher blood glucose concentrations are associated with a higher risk for developing micro- and macrovascular complications, evidence for a beneficial effect of antihyperglycaemic therapy in patients with type 2 diabetes mellitus is conflicting. Two large studies, the United Kingdom Prospective Diabetes Study (UKPDS) and the University Group Diabetes Program (UGDP), did not find a reduction of cardiovascular endpoints through improvement of metabolic control. The theoretical benefits of newer insulin analogues might result in fewer macrovascular and microvascular events.
OBJECTIVES
To assess the effects of long-term treatment with long-acting insulin analogues (insulin glargine and insulin detemir) compared to NPH insulin in patients with type 2 diabetes mellitus.
SEARCH STRATEGY
Studies were obtained from computerised searches of MEDLINE, EMBASE, The Cochrane Library and communication with experts in the field as well as insulin producing companies.
SELECTION CRITERIA
Studies were included if they were randomised controlled trials in adults with diabetes mellitus type 2 and had a trial duration of at least 24 weeks.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data. Pooling of studies by means of random-effects meta-analyses was performed.
MAIN RESULTS
Six studies comparing insulin glargine to NPH (Neutral Protamine Hagedorn) insulin and two studies comparing insulin detemir to NPH insulin were identified. In these trials, 1715 patients were randomised to insulin glargine and 578 patients to insulin detemir. Duration of the included trials ranged from 24 to 52 weeks. Metabolic control, measured by glycosylated haemoglobin A1c (HbA1c) as a surrogate endpoint, and adverse effects did not differ in a clinical relevant way between treatment groups. While no statistically significant difference for severe hypoglycaemia rates was shown in any of the trials, the rate of symptomatic, overall and nocturnal hypoglycaemia was statistically significantly lower in patients treated with either insulin glargine or detemir. No evidence for a beneficial effect of long-acting analogues on patient-oriented outcomes like mortality, morbidity, quality of life or costs could be obtained.
AUTHORS' CONCLUSIONS
Our analysis suggests, if at all only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2 treated with "basal" insulin regarding symptomatic nocturnal hypoglycaemic events. Until long-term efficacy and safety data are available, we suggest a cautious approach to therapy with insulin glargine or detemir.
Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Randomized Controlled Trials as Topic
PubMed: 17443605
DOI: 10.1002/14651858.CD005613.pub3 -
Journal of Diabetes and Its... 2007Despite the evidence-based approach to management of Type 2 diabetes outlined in current diabetes practice guidelines, a large proportion of patients are achieving... (Review)
Review
Despite the evidence-based approach to management of Type 2 diabetes outlined in current diabetes practice guidelines, a large proportion of patients are achieving suboptimal glycemic control. A substantial amount of data exists comparing insulin glargine and neutral protamine Hagedorn (NPH) insulin for long-acting basal insulin coverage. The objective of this systematic review was to provide a balanced appraisal of existing clinical evidence and to determine the appropriate step in therapy for insulin glargine or NPH insulin. Relevant English language articles from 1996 to 2005 were identified through searches of the National Center for Biotechnology Information PubMed database. Search terms included neutral protamine Hagedorn, NPH, insulin glargine, insulin therapy, Type 2 diabetes, insulin analogs, HOE901, and HOE-901. Studies were compared regarding designs, primary and secondary efficacy parameters, glycosylated hemoglobin A1c (A1C), fasting plasma glucose (FPG), incidence of hypoglycemia, and other safety assessments. Six original multicenter, randomized, open-label, parallel-group trials conducted in Europe or the United States, ranging in duration from 4 to 52 weeks, met the inclusion criteria. Two additional analyses represented a subanalysis and a study extension. All of the studies compared insulin glargine with NPH insulin given once or twice daily as monotherapy or in conjunction with oral antidiabetic agents in patients with Type 2 diabetes. Based on available evidence, insulin glargine has shown equal clinical efficacy to that of NPH insulin and similar reductions in A1C and is associated with similar or lower FPG levels. Recent studies also have demonstrated that less frequent nocturnal hypoglycemia incidence is associated with insulin glargine compared with NPH insulin. The known pathophysiology of Type 2 diabetes and the need for basal insulin treatment are presented as rationale for comparison of these insulins.
Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting
PubMed: 17493554
DOI: 10.1016/j.jdiacomp.2007.01.001 -
The Patient Aug 2018Insulin analog glargine (GLA) has been available as one of the therapeutic options for patients with type 1 diabetes mellitus to enhance glycemic control. Studies have...
INTRODUCTION
Insulin analog glargine (GLA) has been available as one of the therapeutic options for patients with type 1 diabetes mellitus to enhance glycemic control. Studies have shown that a decrease in the frequency of hypoglycemic episodes improves the quality of life (QoL) of diabetic patients. However, there are appreciable acquisition cost differences between different insulins. Consequently, there is a need to assess their impact on QoL to provide future guidance to health authorities.
METHOD
A systematic review of multiple databases including Medline, LILACS, Cochrane, and EMBASE databases with several combinations of agreed terms involving randomized controlled trials and cohorts, as well as manual searches and gray literature, was undertaken. The primary outcome measure was a change in QoL. The quality of the studies and the risk of bias was also assessed.
RESULTS
Eight studies were eventually included in the systematic review out of 634 publications. Eight different QoL instruments were used (two generic, two mixed, and four specific), in which the Diabetes Treatment Satisfaction Questionnaire (DTSQ) was the most used. The systematic review did not consistently show any significant difference overall in QoL scores, whether as part of subsets or combined into a single score, with the use of GLA versus neutral protamine Hagedorn (NPH) insulin. Only in patient satisfaction measured by DTSQ was a better result consistently seen with GLA versus NPH insulin, but not using the Well-being Inquiry for Diabetics (WED) scale. However, none of the cohort studies scored a maximum on the Newcastle-Ottawa scale for quality, and they generally were of moderate quality with bias in the studies.
CONCLUSION
There was no consistent difference in QoL or patient-reported outcomes when the findings from the eight studies were collated. In view of this, we believe the current price differential between GLA and NPH insulin in Brazil cannot be justified by these findings.
Topics: Blood Glucose; Brazil; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Patient Satisfaction; Quality of Life
PubMed: 29322308
DOI: 10.1007/s40271-017-0291-3 -
The Cochrane Database of Systematic... Oct 2020The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes (CFRD) has been diagnosed. Diagnosis is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes (CFRD) has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/L (125 mg/dL); or oral glucose tolerance tests greater than 11.11 mmol/L (200 mg/dL) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/L (200 mg/dL); or glycated hemoglobin levels of at least 6.5%. This is an update of a previously published review.
OBJECTIVES
To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences. Date of most recent register search: 10 September 2020. We searched online trials registries; date of most recent searches: 21 March 2020.
SELECTION CRITERIA
Randomized controlled trials comparing all methods of pharmacological diabetes therapy in people with diagnosed CFRD.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed the risk of bias in the included studies. Authors also used GRADE to assess the quality of the evidence.
MAIN RESULTS
The searches identified 29 trials (45 references). Four included trials provide results: one short-term single-center cross-over trial (seven adults) comparing insulin with oral repaglinide and no medication in adults with CFRD and normal fasting glucose; one long-term multicenter trial (61 adults with CFRD) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (67 adults) comparing insulin with oral repaglinide; and one 12-week single-center cross-over trial (20 adults) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin. Two ongoing trials of newly approved incretin mimics have been noted for possible future inclusion. Downgrading of the quality of the evidence was mainly due to risks of bias across all domains, but particularly due to concerns surrounding allocation concealment and selective reporting. There were also some concerns due to imprecision from small sample sizes and low event rates. Finally, there may be some bias due to the amounts of insulin and repaglinide given not being comparable. Data from one trial comparing insulin to placebo (39 participants) did not show any difference between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) or nutritional status (low-quality evidence). Similarly, no differences between groups were seen for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or quality of life (QoL). These results were mirrored in the narrative reports for the second trial in this comparison (seven participants). Data from the one-year trial comparing repaglinide to placebo (38 participants), showed no differences between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) and nutritional status (low-quality evidence). Also, no differences were seen between groups for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or QoL. These findings were mirrored in the narrative reports for the second trial (n = 7) in this comparison. Three trials compared insulin to repaglinide (119 participants). Data from one trial (n = 67) showed no difference in blood glucose levels at either 12 months (high-quality evidence) or 24 months; narrative reports from one trial (45 participants) reported no difference between groups, but the second trial (7 participants) reported a beneficial effect of insulin over repaglinide. Two trials (112 participants) found no difference between insulin and repaglinide in lung function or nutritional status (moderate-quality evidence). Two trials (56 participants) reported no difference in the number of hypoglycemic episodes (low-quality evidence). One trial (45 participants) reported no difference between groups in secondary infections and cystic fibrosis QoL. The single trial comparing glargine to neutral protamine Hagedorn insulin did not report directly on the review's primary outcomes, but did report no differences between groups in post-prandial glucose values and weight; neither group reported infectious complications. There was no difference in episodes of hypoglycemia (very low-quality evidence) and while there was no difference reported in QoL, all participants opted to continue treatment with glargine after the trial was completed. Mortality was not reported by any trial in any comparison, but death was not given as a reason for withdrawal in any trial.
AUTHORS' CONCLUSIONS
This review has not found any conclusive evidence that any agent has a distinct advantage over another in controlling hyperglycemia or the clinical outcomes associated with CFRD. Given the treatment burden already experienced by people with cystic fibrosis, oral therapy may be a viable treatment option. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes and its impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority. Specifically, investigators should evaluate adherence to different therapies and also whether there is benefit in using additional hypoglycemic agents as well as the newly approved incretin mimics. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should also be further investigated as adjuvant therapy to insulin.
Topics: Administration, Oral; Bias; Blood Glucose; Carbamates; Cystic Fibrosis; Diabetes Mellitus; Fasting; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Piperidines; Randomized Controlled Trials as Topic
PubMed: 33075159
DOI: 10.1002/14651858.CD004730.pub5 -
Clinical Therapeutics Jun 2003Insulin glargine is the first long-acting basal insulin analogue indicated for subcutaneous administration once daily at bedtime in adults with type 1 or type 2 diabetes... (Review)
Review
BACKGROUND
Insulin glargine is the first long-acting basal insulin analogue indicated for subcutaneous administration once daily at bedtime in adults with type 1 or type 2 diabetes mellitus and pediatric patients aged > or = 6 years with type 1 diabetes. It differs in structure from native human insulin by 3 amino acids, a structural modification that provides a delayed onset of action and a constant, peakless effect that has a duration of at least 24 hours.
OBJECTIVE
The goal of this article was to help determine the current place in therapy of insulin glargine by reviewing all available efficacy and tolerability data published since its introduction onto the market.
METHODS
Relevant English-language articles were identified through searches of MEDLINE, PubMed, and EMBASE from 1966 to October 2002 and PREMEDLINE for November 2002. The search terms used were insulin, analogs, analogues, diabetes mellitus, glargine, HOE901, HOE-901, efficacy, safety, comparative study, treatment outcome, and case report. The reference lists of the identified articles were searched for additional relevant publications. Pharmacokinetic and pharmacodynamic data were reviewed and summarized. All large clinical trials (> or = 100 patients) evaluating the efficacy and tolerability of insulin glargine in patients with type 1 or type 2 diabetes were included in the review. Studies were compared in terms of their designs, primary and secondary efficacy parameters (glycosylated hemoglobin [HbA(1c)], fasting plasma glucose [FPG] and/or fasting blood glucose [FBG] level, incidence of hypoglycemia), and tolerability assessments.
RESULTS
Fourteen trials met the criteria for inclusion in this review, 7 of them published only in abstract form. All were multicenter, randomized, open-label, parallel-group trials conducted in Europe or the United States, and ranged in duration from 4 to 52 weeks. They compared insulin glargine with neutral protamine Hagedorn (NPH) insulin given once or twice daily in >5000 patients with type 1 or type 2 diabetes, or in insulin-naive patients with type 2 diabetes that was poorly controlled by oral antidiabetic agents. Insulin doses were individually titrated to achieve a target FBG level < or =120 mg/dL (6.7 mmol/L). The studies were typically statistically underpowered to detect a significant difference in HbA(1c) between treatment groups; only 3 trials were of an adequate size to have 90% statistical power to detect a mean 0.5% difference in HbA(1c). Furthermore, analysis of the data from these trials was associated with a number of methodologic problems relating to inconsistencies in reporting. Given these limitations, the available data suggest that insulin glargine treatment produces statistically significant reductions in FPG or FBG levels at end point both compared with baseline and compared with NPH insulin (P < 0.001) without achieving overall significant improvements in HbA(1c) values. However, a recent abstract of a small 52-week trial in patients with type 1 diabetes reported a 0.4% additional decrease in HbA(1c) with insulin glargine treatment compared with NPH insulin. Patients have reported greater treatment satisfaction with insulin glargine compared with NPH insulin. The findings varied regarding weight gain, overall incidence of hypoglycemia, and incidence of nocturnal hypoglycemia. Currently, the cost of insulin glargine is twice that of NPH insulin on a per-unit basis.
CONCLUSIONS
As a basal insulin replacement, insulin glargine administered once daily demonstrates a steady time-action profile over 24 hours without a pronounced peak. Based on the evidence from published clinical trials, insulin glargine appears to have equal clinical efficacy to NPH insulin, produces similar reductions in HbA(1c), and is associated with lower FPG and FBG levels and a consistent and significant reduction in the incidence of nocturnal hypoglycemia in patients with type 2 diabetes.
Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Quality of Life
PubMed: 12860485
DOI: 10.1016/s0149-2918(03)80156-x