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Diabetes Therapy : Research, Treatment... Jun 2016The use of insulin analogs for the treatment of type 1 diabetes mellitus (T1DM) is widespread; however, the therapeutic benefits still require further evaluation given...
INTRODUCTION
The use of insulin analogs for the treatment of type 1 diabetes mellitus (T1DM) is widespread; however, the therapeutic benefits still require further evaluation given their higher costs. The objective of this study was to evaluate the effectiveness and safety of analog insulin glargine compared to recombinant DNA (rDNA) insulin in patients with T1DM in observational studies, building on previous reviews of randomized controlled trials comparing neutral protamine Hagedorn insulin and insulin glargine.
METHODS
A systematic review with a meta-analysis was performed. The review included cohort studies and registries available on PubMed, LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as manual and gray literature searches. The meta-analysis was conducted in Review Manager 5.3 software. The primary outcomes were glycated hemoglobin (Hb1Ac), weight gain, and hypoglycemia. Methodological quality was assessed using the Newcastle-Ottawa scale.
RESULTS
Out of 796 publications, 11 studies were finally included. The meta-analysis favored insulin glargine in HbA1c outcomes (adult patients) and hypoglycemic episodes (P < 0.05), but without reaching glycemic control (Hb1Ac to approximately 7%). The methodological quality of the studies was moderate, noting that 45% of studies were funded by pharmaceutical companies.
CONCLUSION
Given the high heterogeneity of the studies, the discrete value presented by the estimated effect on effectiveness and safety, potential conflicts of interest of the studies, and the appreciable higher cost of insulin glargine, there is still no support for recommending first-line therapy with analogs. The role of analogs in the treatment of T1DM could be better determined by further observational studies of good methodological quality to assess their long-term effectiveness and safety, as well as their cost-effectiveness.
PubMed: 27048292
DOI: 10.1007/s13300-016-0166-y -
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 -
Acta Diabetologica Aug 2015A variety of basal insulin preparations are used to treat patients with type 2 diabetes mellitus (T2DM). We aimed to summarize scientific evidence on relative efficacy... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis of randomized clinical trials comparing efficacy and safety outcomes of insulin glargine with NPH insulin, premixed insulin preparations or with insulin detemir in type 2 diabetes mellitus.
AIMS
A variety of basal insulin preparations are used to treat patients with type 2 diabetes mellitus (T2DM). We aimed to summarize scientific evidence on relative efficacy and safety of insulin glargine (IGlar) and other insulins in T2DM.
METHODS
A systematic review was carried out in major medical databases up to December 2012. Relevant studies compared efficacy and safety of IGlar, added to oral drugs (OAD) or/and in combination with bolus insulin, with protamine insulin (NPH) or premixed insulin (MIX) in the same regimen, as well as with insulin detemir (IDet), in T2DM. Target HbA1c level without hypoglycemic events was considered the primary endpoint.
RESULTS
Twenty eight RCTs involving 12,669 T2DM patients followed for 12-52 weeks were included in quantitative analysis. IGlar + OAD use was associated with higher probability of reaching target HbA1c level without hypoglycemia as compared to NPH + OAD (RR = 1.32 [1.09, 1.59]) or MIX without OAD (RR = 1.61 [1.22, 2.13]) and similar effect as IDet + OAD (RR = 1.07 [0.87, 1.33]) and MIX + OAD (RR = 1.09 [0.86, 1.38]). IGlar + OAD demonstrated significantly lower risk of symptomatic hypoglycemia as compared to NPH + OAD (RR = 0.89 [0.83, 0.96]), MIX + OAD (RR = 0.75 [0.68, 0.83]) and MIX without OAD(RR = 0.75 [0.68, 0.83]), but not with IDet + OAD (RR = 0.99 [0.90, 1.08]). In basal-bolus regimens, IGlar demonstrated similar proportion of T2DM patients achieving target HbA1c as compared to NPH (RR = 1.14 [0.91, 1.44]) but higher than MIX (RR = 1.26 [1.12, 1.42) or IDet (RR = 1.38 [1.11, 1.72]). The risk of severe hypoglycemia was lower in IGlar than in NPH (RR = 0.77 [0.63, 0.94]), with no differences in comparison with MIX (RR = 0.74 [0.46, 1.20]) and IDet (RR = 1.10 [0.54, 2.25]). IGlar + OAD has comparable safety profile to NPH, with less frequent adverse events leading to treatment discontinuation than MIX + OAD (RR = 0.41 [0.22, 0.76]) and IDet + OAD (RR = 0.40 [0.24, 0.69]). Also severe adverse reactions were less common for IGlar + OAD when compared to MIX + OAD (RR = 0.71 [0.52; 0.98]).
CONCLUSION
For the majority of examined efficacy and safety outcomes, IGlar use in T2DM patients was superior or non-inferior to the alternative insulin treatment options.
Topics: Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25585592
DOI: 10.1007/s00592-014-0698-4 -
BMJ Open Dec 2014To evaluate the effectiveness and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors versus intermediate-acting insulin for adults with type 2 diabetes mellitus (T2DM)... (Comparative Study)
Comparative Study Meta-Analysis Review
Safety and effectiveness of dipeptidyl peptidase-4 inhibitors versus intermediate-acting insulin or placebo for patients with type 2 diabetes failing two oral antihyperglycaemic agents: a systematic review and network meta-analysis.
OBJECTIVE
To evaluate the effectiveness and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors versus intermediate-acting insulin for adults with type 2 diabetes mellitus (T2DM) and poor glycaemic control despite treatment with two oral agents.
SETTING
Studies were multicentre and multinational.
PARTICIPANTS
Ten studies including 2967 patients with T2DM.
INTERVENTIONS
Studies that examined DPP-4 inhibitors compared with each other, intermediate-acting insulin, no treatment or placebo in patients with T2DM.
PRIMARY AND SECONDARY OUTCOME MEASURES
Primary outcome was glycosylated haemoglobin (HbA1c). Secondary outcomes were healthcare utilisation, body weight, fractures, quality of life, microvascular complications, macrovascular complications, all-cause mortality, harms, cost and cost-effectiveness.
RESULTS
10 randomised clinical trials with 2967 patients were included after screening 5831 titles and abstracts, and 180 full-text articles. DPP-4 inhibitors significantly reduced HbA1c versus placebo in network meta-analysis (NMA; mean difference (MD) -0.62%, 95% CI -0.93% to -0.33%) and meta-analysis (MD -0.61%, 95% CI -0.81% to -0.41%), respectively. Significant differences in HbA1c were not observed for neutral protamine Hagedorn (NPH) insulin versus placebo and DPP-4 inhibitors versus NPH insulin in NMA. In meta-analysis, no significant differences were observed between DPP-4 inhibitors and placebo for severe hypoglycaemia, weight gain, cardiovascular disease, overall harms, treatment-related harms and mortality, although patients receiving DPP-4 inhibitors experienced less infections (relative risk 0.72, 95% CI 0.57 to 0.91).
CONCLUSIONS
DPP-4 inhibitors were superior to placebo in reducing HbA1c levels in adults with T2DM taking at least two oral agents. Compared with placebo, no safety signals were detected with DPP-4 inhibitors and there was a reduced risk of infection. There was no significant difference in HbA1c observed between NPH and placebo or NPH and DPP-4 inhibitors.
TRIAL REGISTRATION NUMBER
PROSPERO # CRD42013003624.
Topics: Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Incretins; Insulin; Insulin, Isophane; Treatment Outcome
PubMed: 25537781
DOI: 10.1136/bmjopen-2014-005752 -
BMJ (Clinical Research Ed.) Oct 2014To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes. (Comparative Study)
Comparative Study Meta-Analysis Review
Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis.
OBJECTIVE
To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Medline, Cochrane Central Register of Controlled Trials, Embase, and grey literature were searched through January 2013.
STUDY SELECTION
Randomized controlled trials or non-randomized studies of long acting (glargine, detemir) and intermediate acting (neutral protamine Hagedorn (NPH), lente) insulin for adults with type 1 diabetes were included.
RESULTS
39 studies (27 randomized controlled trials including 7496 patients) were included after screening of 6501 titles/abstracts and 190 full text articles. Glargine once daily, detemir once daily, and detemir once/twice daily significantly reduced hemoglobin A1c compared with NPH once daily in network meta-analysis (26 randomized controlled trials, mean difference -0.39%, 95% confidence interval -0.59% to -0.19%; -0.26%, -0.48% to -0.03%; and -0.36%, -0.65% to -0.08%; respectively). Differences in network meta-analysis were observed between long acting and intermediate acting insulin for severe hypoglycemia (16 randomized controlled trials; detemir once/twice daily versus NPH once/twice daily: odds ratio 0.62, 95% confidence interval 0.42 to 0.91) and weight gain (13 randomized controlled trials; detemir once daily versus NPH once/twice daily: mean difference 4.04 kg, 3.06 to 5.02 kg; detemir once/twice daily versus NPH once daily: -5.51 kg, -6.56 to -4.46 kg; glargine once daily versus NPH once daily: -5.14 kg, -6.07 to -4.21). Compared with NPH, detemir was less costly and more effective in 3/14 cost effectiveness analyses and glargine was less costly and more effective in 2/8 cost effectiveness analyses. The remaining cost effectiveness analyses found that detemir and glargine were more costly but more effective than NPH. Glargine was not cost effective compared with detemir in 2/2 cost effectiveness analyses.
CONCLUSIONS
Long acting insulin analogs are probably superior to intermediate acting insulin analogs, although the difference is small for hemoglobin A1c. Patients and their physicians should tailor their choice of insulin according to preference, cost, and accessibility.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42013003610.
Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin, Long-Acting
PubMed: 25274009
DOI: 10.1136/bmj.g5459