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The Journal of Clinical Endocrinology... Jul 2022Individuals with diabetes or newly recognized hyperglycemia account for over 30% of noncritically ill hospitalized patients. Management of hyperglycemia in these... (Meta-Analysis)
Meta-Analysis
A Systematic Review Supporting the Endocrine Society Clinical Practice Guideline for the Management of Hyperglycemia in Adults Hospitalized for Noncritical Illness or Undergoing Elective Surgical Procedures.
CONTEXT
Individuals with diabetes or newly recognized hyperglycemia account for over 30% of noncritically ill hospitalized patients. Management of hyperglycemia in these patients is challenging.
OBJECTIVE
To support development of the Endocrine Society Clinical Practice Guideline for management of hyperglycemia in adults hospitalized for noncritical illness or undergoing elective surgical procedures.
METHODS
We searched several databases for studies addressing 10 questions provided by a guideline panel from the Endocrine Society. Meta-analysis was conducted when feasible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess certainty of evidence.
RESULTS
We included 94 studies reporting on 135 553 patients. Compared with capillary blood glucose, continuous glucose monitoring increased the number of patients identified with hypoglycemia and decreased mean daily blood glucose (BG) (very low certainty). Data on continuation of insulin pump therapy in hospitalized adults were sparse. In hospitalized patients receiving glucocorticoids, combination neutral protamine hagedorn (NPH) and basal-bolus insulin was associated with lower mean BG compared to basal-bolus insulin alone (very low certainty). Data on NPH insulin vs basal-bolus insulin in hospitalized adults receiving enteral nutrition were inconclusive. Inpatient diabetes education was associated with lower HbA1c at 3 and 6 months after discharge (moderate certainty) and reduced hospital readmissions (very low certainty). Preoperative HbA1c level < 7% was associated with shorter length of stay, lower postoperative BG and a lower number of neurological complications and infections, but a higher number of reoperations (very low certainty). Treatment with glucagon-like peptide-1 agonists or dipeptidyl peptidase-4 inhibitors in hospitalized patients with type 2 diabetes and mild hyperglycemia was associated with lower frequency of hypoglycemic events than insulin therapy (low certainty). Caloric oral fluids before surgery in adults with diabetes undergoing surgical procedures did not affect outcomes (very low certainty). Counting carbohydrates for prandial insulin dosing did not affect outcomes (very low certainty). Compared with scheduled insulin (basal-bolus or basal insulin + correctional insulin), correctional insulin was associated with higher mean daily BG and fewer hypoglycemic events (low certainty).
CONCLUSION
The certainty of evidence supporting many hyperglycemia management decisions is low, emphasizing importance of shared decision-making and consideration of other decisional factors.
Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Elective Surgical Procedures; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin
PubMed: 35690929
DOI: 10.1210/clinem/dgac277 -
Scandinavian Journal of Surgery : SJS :... Jun 2021Acute mesenteric venous thrombosis accounts for up to 20% of all patients with acute mesenteric ischemia in high-income countries. Acute mesenteric venous thrombosis is...
BACKGROUND AND AIMS
Acute mesenteric venous thrombosis accounts for up to 20% of all patients with acute mesenteric ischemia in high-income countries. Acute mesenteric venous thrombosis is nowadays relatively more often diagnosed with intravenous contrast-enhanced computed tomography in the portal phase than at explorative laparotomy No high-quality comparative studies between anticoagulation alone, endovascular therapy, or surgery exists. The aim of the present systematic review was to offer a contemporary overview on management.
MATERIALS AND METHODS
Eleven relevant published original studies with series of at least ten patients were retrieved from a Pub Med search between 2015 and 2020 using the Medical Subject Heading term "mesenteric venous thrombosis."
RESULTS
When MVT is diagnosed early, immediate anticoagulation with either unfractionated heparin or subcutaneous low-molecular-weight heparin should commence. Surgeons need to be aware of the importance to scrutinize the computed tomography images themselves for assessment of secondary intestinal abnormalities to mesenteric venous thrombosis and the risk of bowel resection and worse prognosis. Progression toward peritonitis is an indication for explorative laparotomy and assessment of bowel viability. Frank transmural small bowel necrosis should be resected and bowel anastomosis may be delayed for several days until second look. Meanwhile, intravenous full-dose unfractionated heparin should be given at the end of the first operation. Postoperative major intra-abdominal or gastrointestinal bleeding occurs rarely, but the heparin effect can instantaneously be reversed by . Patients who do not improve during conservative therapy with anticoagulation alone but without developing peritonitis may be subjected to endovascular therapy in expert centers. When the patient's intestinal function has recovered, with or without bowel resection, switch from parenteral unfractionated heparin or low-molecular-weight heparin therapy to oral anticoagulation can be performed. There is a trend that direct oral anticoagulants are increasingly used instead of vitamin K antagonists. Up to now, direct oral anticoagulants have been shown to be equally effective with the same rate of bleeding complications. Patients with no strong permanent trigger factor for mesenteric venous thrombosis such as intra-abdominal cancer should undergo blood screening for inherited and acquired thrombophilia.
CONCLUSION
Early diagnosis with emergency computed tomography with intravenous contrast-enhancement and imaging in the portal phase and anticoagulation therapy is necessary to be able to have a succesful non-operative succesful course.
Topics: Anticoagulants; Heparin; Humans; Mesenteric Ischemia; Mesenteric Veins; Venous Thrombosis
PubMed: 33118463
DOI: 10.1177/1457496920969084 -
Andrology Sep 2016Existing literature suggests evidence that protamine deficiency is related to DNA damage and male fertility. In this meta-analysis, we analyzed the relationship between... (Meta-Analysis)
Meta-Analysis Review
Existing literature suggests evidence that protamine deficiency is related to DNA damage and male fertility. In this meta-analysis, we analyzed the relationship between the ratio of protamine-1 and protamine-2 with male fertility and the association of protamine deficiency with sperm DNA damage. Quality of available cohort studies was evaluated using the Newcastle-Ottawa Scale checklist. Summary effect estimates with 95% confidence intervals (CI) were derived using a random effects model. The effect of the protamine ratio on male fertility was analyzed in nine studies demonstrating a significantly higher value of the protamine ratio in subfertile men (n = 633) when compared with controls (n = 453, SMD = 0.46, 95% CI 0.25-0.66, Z = 4.42, p < 0.00001). Both protamine mRNA (SMD = 0.45, 95% CI 0.11-0.79, Z = 2.63, p = 0.009) and protein ratio (SMD = 0.46, 95% CI 0.25-0.68, Z = 4.22, p < 0.0001) showed significantly increased values in subfertile patients. The association between protamine deficiency and DNA damage was analyzed in 12 studies (n = 845) exhibiting a combined overall correlation coefficient (COR) of 0.53 (95% CI 0.28-0.71, Z = 3.87, p < 0.001). Protamine deficiency measured by CMA3 staining was significantly associated with sperm DNA damage (COR = 0.71, 95% CI 0.48-0.85, Z = 4.87, p < 0.001), whereas the P1/P2 ratio was not (COR = 0.17, 95% CI -0.16 to 0.46, Z = 0.99, p = 0.33). It is concluded that the protamine ratio represents a suitable biomarker for the assessment of sperm quality and protamine deficiency is closely related with sperm DNA damage.
Topics: DNA Damage; DNA Fragmentation; Humans; Infertility, Male; Male; Protamines; Spermatozoa
PubMed: 27231200
DOI: 10.1111/andr.12216 -
Reviews in Cardiovascular Medicine Jan 2022Perioperative anticoagulation management with uninterrupted or minimally interrupted anticoagulation during atrial fibrillation (AF) ablation is thought to be critical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Perioperative anticoagulation management with uninterrupted or minimally interrupted anticoagulation during atrial fibrillation (AF) ablation is thought to be critical to minimize thromboembolic complications. Protamine is often administered to neutralize the effects of heparin and expedite vascular hemostasis post-procedure.
OBJECTIVE
We performed a systematic review and meta-analysis to determine the effectiveness of protamine to expedite vascular hemostasis and ambulation in patients undergoing AF ablation.
METHODS
Electronic searches on PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from the inception through August 7, 2021, were performed. The primary outcomes included-time to hemostasis (minutes) and time to ambulation (minutes). The secondary outcomes included - any vascular complications (excluding minor hematoma), minor hematoma, or cerebrovascular accidents (CVA).
RESULTS
A total of 5 eligible studies (3 retrospective cohort studies and two randomized trials) consisting of 1012 patients (515 patients received protamine group and 497 patients did not receive protamine group) were included in the meta-analysis. There was a significant reduction in time to ambulation [weighted mean difference (WMD) -176.6 minutes, 95% Confidence interval (CI) -266.9 to -86.3; < 0.01] and time to hemostasis (WMD -13.72 minutes, 95% CI -22 to -5.4, < 0.01) in the protamine group compared to the contrary. At a follow-up up to 3 months, there was no statistical difference between the two groups with regards to vascular complications (2.9% vs. 7.4%; Risk ratio (RR) 0.46 95% CI 0.17 to 1.24; = 0.12), minor hematoma (2.1% vs. 5.8%; RR 0.43, 95% CI 0.16 to 1.2; = 0.11) or CVA (0 vs. 0.3%; RR 0.62, 95% CI 0.08 to 4.98; = 0.65).
CONCLUSION
Protamine administration was associated with reduced time to ambulation (176 minutes reduction) and time to hemostasis (13 minutes reduction) without an increase in any adverse events.
Topics: Anticoagulants; Atrial Fibrillation; Catheter Ablation; Humans; Protamines; Retrospective Studies; Treatment Outcome
PubMed: 35092226
DOI: 10.31083/j.rcm2301034 -
Journal of Diabetes Jun 2023The objective of this study was to provide recommendations regarding effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting... (Review)
Review
The objective of this study was to provide recommendations regarding effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting plasma glucose of five basal insulins (glargine U-300, degludec U-100, glargine U-100, detemir, and insulin protamine Hagedorn) in insulin-naïve adult patients with type 2 diabetes in the Asia-Pacific region. Based on evidence from a systematic review, we developed an Asia-Pacific clinical practice guideline through comprehensive internal review and external review processes. We set up and used clinical thresholds of trivial, small, moderate, and large effects for different critical and important outcomes in the overall certainty of evidence assessment and balancing the magnitude of intervention effects when making recommendations, following GRADE methods (Grading of Recommendations, Assessment, Development, and Evaluation). The AGREE (Appraisal of Guidelines, Research and Evaluation) and RIGHT (Reporting Items for practice Guidelines in HealThcare) guideline reporting checklists were complied with. After the second-round vote by the working group members, all the recommendations and qualifying statements reached over 75% agreement rates. Among 44 contacted external reviewers, we received 33 clinicians' and one patient's comments. The overall response rate was 77%. To solve the four research questions, we made two strong recommendations, six conditional recommendations, and two qualifying statements. Although the intended users of this guideline focused on clinicians in the Asia-Pacific region, the eligible evidence was based on recent English publications. We believe that the recommendations and the clinical thresholds set up in the guideline can be references for clinicians who take care of patients with type 2 diabetes worldwide.
Topics: Humans; Adult; Diabetes Mellitus, Type 2; Insulin Glargine; Insulin; Insulin, Long-Acting; Asia
PubMed: 37088916
DOI: 10.1111/1753-0407.13392 -
Cureus Feb 2024The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the... (Review)
Review
BACKGROUND
The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the heterogeneous response to heparin in each patient. On the other hand, the literature is inconclusive on whether individualized anticoagulation management based on real-time blood heparin concentration improves post-CBP outcomes.
METHODS
We searched databases of Medline, Excerpta Medica dataBASE (EMBASE), PubMed, Cumulative Index to Nursing and Allied Health Literature (CINHL), and Google Scholar, recruiting randomized controlled trials (RCTs) and prospective studies comparing the outcomes of dosing heparin and/or protamine based on measured heparin concentration versus patient's total body weight for CPB. Random effects meta-analyses and meta-regression were conducted to compare the outcome profiles. Primary endpoints include postoperative blood loss and the correlation with heparin and protamine doses, the reversal protamine and loading heparin dose ratio; secondary endpoints included postoperative platelet counts, antithrombin III, fibrinogen levels, activated prothrombin time (aPTT), incidences of heparin rebound, and re-exploration of chest wound for bleeding.
RESULTS
Twenty-six studies, including 22 RCTs and four prospective cohort studies involving 3,810 patients, were included. Compared to body weight-based dosing, patients of individualized, heparin concentration-based group had significantly lower postoperative blood loss (mean difference (MD)=49.51 mL, 95% confidence interval (CI): 5.33-93.71), lower protamine-to-heparin dosing ratio (MD=-0.20, 95% CI: -0.32 ~ -0.12), and higher early postoperative platelet counts (MD=8.83, 95% CI: 2.07-15.59). The total heparin doses and protamine reversal were identified as predictors of postoperative blood loss by meta-regression.
CONCLUSIONS
There was a significant correlation between the doses of heparin and protamine with postoperative blood loss; therefore, précised dosing of both could be critical for reducing bleeding and transfusion requirements. Data from the enrolled studies indicated that compared to conventional weight-based dosing, individualized, blood concentration-based heparin and protamine dosing may have outcome benefits reducing postoperative blood loss. The dosing calculation of heparin based on the assumption of a one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model and linear relationship between the calculated dose and blood heparin concentration may be inaccurate. With the recent advancement of the technologies of machine learning, individualized, precision management of anticoagulation for CPB may be possible in the near future.
PubMed: 38357407
DOI: 10.7759/cureus.54144 -
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 (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 -
Frontiers in Endocrinology 2024The comparative effectiveness of basal insulins has been examined in several studies. However, current treatment algorithms provide a list of options with no clear... (Meta-Analysis)
Meta-Analysis
AIM
The comparative effectiveness of basal insulins has been examined in several studies. However, current treatment algorithms provide a list of options with no clear differentiation between different basal insulins as the optimal choice for initiation.
METHODS
A comprehensive search of MEDLINE, Embase, Cochrane Library, ISI, and Scopus, and a reference list of retrieved studies and reviews were performed up to November 2023. We identified phase III randomized controlled trials (RCTs) comparing the efficacy and safety of basal insulin regimens. The primary outcomes evaluated were HbA1c reduction, weight change, and hypoglycemic events. The revised Cochrane ROB-2 tool was used to assess the methodological quality of the included studies. A random-effects frequentist network meta-analysis was used to estimate the pooled weighted mean difference (WMD) and odds ratio (OR) with 95% confidence intervals considering the critical assumptions in the networks. The certainty of the evidence and confidence in the rankings was assessed using the GRADE minimally contextualized approach.
RESULTS
Of 20,817 retrieved studies, 44 RCTs (23,699 participants) were eligible for inclusion in our network meta-analysis. We found no significant difference among various basal insulins (including Neutral Protamine Hagedorn (NPH), ILPS, insulin glargine, detemir, and degludec) in reducing HbA1c. Insulin glargine, 300 U/mL (IGlar-300) was significantly associated with less weight gain (mean difference ranged from 2.9 kg to 4.1 kg) compared to other basal insulins, namely thrice-weekly insulin degludec (IDeg-3TW), insulin degludec, 100 U/mL (IDeg-100), insulin degludec, 200 U/mL (IDeg-200), NPH, and insulin detemir (IDet), but with low to very low certainty regarding most comparisons. IDeg-100, IDeg-200, IDet, and IGlar-300 were associated with significantly lower odds of overall, nocturnal, and severe hypoglycemic events than NPH and insulin lispro protamine (ILPS) (moderate to high certainty evidence). NPH was associated with the highest odds of overall and nocturnal hypoglycemia compared to others. Network meta-analysis models were robust, and findings were consistent in sensitivity analyses.
CONCLUSION
The efficacy of various basal insulin regimens is comparable. However, they have different safety profiles. IGlar-300 may be the best choice when weight gain is a concern. In contrast, IDeg-100, IDeg-200, IDet, and IGlar-300 may be preferred when hypoglycemia is the primary concern.
Topics: Humans; Insulin Glargine; Insulin, Long-Acting; Glycated Hemoglobin; Network Meta-Analysis; Randomized Controlled Trials as Topic; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Hypoglycemia; Insulin; Weight Gain; Protamines
PubMed: 38586456
DOI: 10.3389/fendo.2024.1286827 -
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