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Frontiers in Endocrinology 2023As a popular antidiabetic drug, teneligliptin has been used for over 10 years, but its efficacy and safety have rarely been systematically evaluated. Therefore, a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
As a popular antidiabetic drug, teneligliptin has been used for over 10 years, but its efficacy and safety have rarely been systematically evaluated. Therefore, a Bayesian network meta-analysis was conducted to evaluate the efficacy and safety of teneligliptin in patients with type 2 diabetes mellitus (T2DM).
METHODS
We systematically searched PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Randomized controlled trials (RCTs) comparing teneligliptin with placebo or active comparators in T2DM patients for at least 12 weeks were included in the study. Data analysis was performed using R 4.2.3 and Stata 17.0 software. Each outcome was presented as a mean difference (MD) or an odds ratio (OR) along with 95% confidence interval (CI) and the surface under the cumulative ranking curve value (SUCRA).
RESULTS
A total of 18 RCTs with 3,290 participants with T2DM were included in this study. Generally, compared to placebo, sitagliptin, vildagliptin, metformin, and bromocriptine, 20 mg of teneligliptin showed better efficacy in reducing HbA1c (MD [95% CI], -0.78 [-0.86 to -0.70], -0.08 [-0.36 to 0.19], -0.04 [-0.72 to 0.60], -0.12 [-0.65 to 0.42], and -0.50 [-0.74 to -0.26], respectively) and fasting plasma glucose (FPG) (MD [95% CI], -18.02 [-20.64 to -15.13], 1.17 [-9.39 to 11.70], -8.06 [-30.95 to 14.35], -2.75 [-18.89 to 13.01], and -34.23 [-45.93 to -22.96], respectively), and 40 mg of teneligliptin also showed better efficacy in reducing HbA1c (MD [95% CI], -0.84 [-1.03 to -0.65], -0.15 [-0.49 to 0.19], -0.10 [-0.81 to 0.57], -0.18 [-0.76 to 0.39], and -0.56 [-0.88 to -0.26], respectively) and FPG (MD [95% CI], -20.40 [-26.07 to -14.57], -1.20 [-13.21 to 10.38], -10.43 [-34.16 to 12.65], -5.13 [-22.21 to 11.66], and -36.61 [-49.33 to -24.01], respectively). Compared to placebo, 20 mg of teneligliptin showed no significant difference in incidences of hypoglycemia and gastrointestinal adverse events (OR [95% CI], 1.30 [0.70 to 2.19] and 1.48 [0.78 to 2.98], respectively), and 40 mg of teneligliptin showed no significant difference in incidence of hypoglycemia (OR [95% CI], 2.63 [0.46 to 8.10]). Generally, antidiabetic effect and hypoglycemia risk of teneligliptin gradually increased as its dose increased from 5 mg to 40 mg. Compared to 20 mg of teneligliptin, 40 mg of teneligliptin showed superior efficacy and no-inferior safety, which was considered as the best option in reducing HbA1c, FPG, and 2h PPG and increasing proportion of the patients achieving HbA1c < 7% (SUCRA, 85.51%, 84.24%, 79.06%, and 85.81%, respectively) among all the included interventions.
CONCLUSION
Compared to sitagliptin, vildagliptin, metformin, bromocriptine, and placebo, teneligliptin displayed favorable efficacy and acceptable safety in treating T2DM. Twenty milligrams or 40 mg per day was the optimal dosage regimen of teneligliptin. The results of this study will provide important evidence-based basis for rational use of teneligliptin and clinical decision-making of T2DM medication.
Topics: Humans; Bromocriptine; Glycated Hemoglobin; Network Meta-Analysis; Vildagliptin; Diabetes Mellitus, Type 2; Metformin; Sitagliptin Phosphate; Hypoglycemic Agents; Hypoglycemia
PubMed: 38189048
DOI: 10.3389/fendo.2023.1282584 -
Annals of Medicine 2023The emergence of genetically-modified human proteins and glucagon-like peptide-1 (GLP-1) receptor agonists have presented a promising strategy for effectively managing... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety profile of once-weekly Semaglutide versus once-daily Sitagliptin as an add-on to metformin in patients with type 2 diabetes: a systematic review and meta-analysis.
BACKGROUND
The emergence of genetically-modified human proteins and glucagon-like peptide-1 (GLP-1) receptor agonists have presented a promising strategy for effectively managing diabetes. Due to the scarcity of clinical trials focusing on the safety and efficacy of semaglutide as an adjunctive treatment for patients with type 2 diabetes who had inadequate glycemic control with metformin, we conducted a systematic review and meta-analysis. This was necessary to fill the gap and provide a comprehensive assessment of semaglutide compared to sitagliptin, a commonly prescribed DPP-4 inhibitor, in this patient population.
METHODS
A comprehensive and systematic search was carried out on reputable databases including PubMed, the Cochrane Library, and Elsevier's ScienceDirect to identify relevant studies that compared the efficacy of once-weekly Semaglutide with once-daily Sitagliptin in individuals diagnosed with type 2 diabetes mellitus. The analysis of the gathered data was performed utilizing the random-effects model, which considers both within-study and between-study variations.
RESULTS
The meta-analysis incorporated three randomized controlled trials (RCTs), encompassing 2401 participants, with a balanced distribution across the treatment groups. The primary focus of the study revolved around evaluating changes in HbA1C, blood pressure, pulse rate, body weight, waist circumference, and BMI. The findings revealed that once-weekly Semaglutide showed substantially improved HbA1C (WMD: -0.98; 95% CI: -1.28, -0.69, p-value: < 0.0001; I2: 100%), systolic (WMD: -3.73; 95% CI: -5.42, -2.04, p-value: <0.0001; I2: 100%) and diastolic blood pressures (WMD: -0.66; 95% CI: -1.02, -0.29, p-value: 0.0005; I2: 100%), and body weight (WMD: -3.17; 95% CI: -3.84, -2.49, p-value: <0.00001; I2: 100%) compared to once-daily Sitagliptin. However, there was an observed increase in pulse rate (WMD: 3.33; 95% CI: 1.61, 5.06, p-value: <0.00001; I2: 100%) associated with Semaglutide treatment. Regarding secondary outcomes, there was an elevated risk of total adverse events and premature treatment discontinuation with Semaglutide. The risk of serious, severe, moderate, and mild adverse events did not significantly differ between the two treatments.
CONCLUSIONS
In conclusion, the administration of once-weekly Semaglutide exhibited a substantial reduction in HbA1c, average systolic blood pressure (SBP), mean diastolic blood pressure (DBP), body weight, waist circumference, body mass index (BMI), and a rise in pulse rate, as opposed to the once-daily administration of Sitagliptin.
Topics: Humans; Metformin; Sitagliptin Phosphate; Glycated Hemoglobin; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Body Weight
PubMed: 37498865
DOI: 10.1080/07853890.2023.2239830 -
Frontiers in Endocrinology 2022The dipeptidyl peptidase-4 inhibitor (DPP-4i) drugs, such as evogliptin, as the second-line drugs for type 2 diabetes mellitus (T2DM) treatment have been reported to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The dipeptidyl peptidase-4 inhibitor (DPP-4i) drugs, such as evogliptin, as the second-line drugs for type 2 diabetes mellitus (T2DM) treatment have been reported to facilitate insulin secretion by reducing glucagon and inhibiting glucagon like peptides. With a vague consensus, the advantageous and non-inferior effects of evogliptin relative to other DPP-4i drugs were recently demonstrated on hemoglobin A1c (HbA1c) levels and overall adverse events in T2DM patients. Thus, the aim was to evaluate the overall influence of evogliptin on HbA1c levels and the adverse events in T2DM patients compared to sitagliptin and linagliptin.
METHODS
Complying with PRISMA guidelines, we conducted a systematic literature search in databases and a meta-analysis. Data about HbA1c levels and the adverse events of T2DM patients were collected and analyzed.
RESULTS
From 1,397 studies, we found five matched studies involving 845 subjects (mean age: 54.7 ± 3 years). The meta-analysis revealed that evogliptin was non-inferior to sitagliptin/linagliptin with a mean difference of 0.062 (95% CI: -0.092 to 0.215. I: 0%. = 0.431) regarding the HbA1c level reduction, and the risk ratio was -0.006 (95% CI: -0.272 to 0.260. I: 1.7%. = 0.966) regarding the adverse effects, indicating no significant difference between evogliptin and linagliptin or sitagliptin in affecting the HbA1c level and adverse effects.
CONCLUSION
The study provides preliminary evidence regarding the similarity in the efficacy of evogliptin compared to other DPP-4i drugs, including sitagliptin and linagliptin, for managing HbA1c levels and adverse events.
Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Linagliptin; Middle Aged; Piperazines; Sitagliptin Phosphate
PubMed: 36060938
DOI: 10.3389/fendo.2022.962385 -
Frontiers in Endocrinology 2022Type 2 diabetes is more common in adults, but is becoming the major concern in children and adolescent recently. This study aimed to provide additional pharmaceutical... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Type 2 diabetes is more common in adults, but is becoming the major concern in children and adolescent recently. This study aimed to provide additional pharmaceutical management for children and adolescents with type 2 diabetes by assessing the efficacy and safety of several glucose-lowering drugs.
METHODS
Searches were performed in PubMed, Medline, Ovid, Cochrane Controlled Register of Trials (CENTRAL), and ClinicalTrials.gov that reported the efficacy and safety of drugs for children and adolescents with type 2 diabetes. Pooled effects were calculated by frequentist fixed effects network meta-analyses and additive network meta-analyses.
RESULTS
A total of 12 trials assessing eight glucose-lowering drugs were included, which compose of seven trials with monotherapy and five trials with combination therapies. Network meta-analysis results showed compared to placebo, saxagliptin+metformin (mean difference (MD) -1.91% [-2.85%, -0.97%]), liraglutide+metformin (MD -1.45% [-1.65%, -1.26%]), and liraglutide (MD -0.90% [-1.35%, -0.45%]) were the top 3 drugs that significantly reduced hemoglobin A1c (HbA1c). Sitagliptin+metformin, dapagliflozin, exenatide-2mcg, linagliptin-5mg, metformin, exenatide-5/10mcg, glimepiride, and sitagliptin also showed significant reduction in HbA1c. There were no significant differences between treatments in the incidence of adverse events, except that liraglutide+metformin had significant adverse effect such as abdominal pain. In addition, dapagliflozin, sitagliptin+metformin, and saxagliptin+metformin showed better efficacy compared with FDA-approved drugs.
CONCLUSIONS
The top 10 treatments of type 2 diabetes in children and adolescents aged 10-17 years were saxagliptin+metformin, liraglutide+metformin, liraglutide, dapagliflozin, exenatide-2 mcg, sitagliptin+metformin, linagliptin-5 mg, linagliptin-1 mg, metformin, and exenatide-5/10 mcg.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=284897, identifier CRD42021284897.
Topics: Adolescent; Adult; Child; Diabetes Mellitus, Type 2; Exenatide; Glucose; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Linagliptin; Liraglutide; Metformin; Network Meta-Analysis; Sitagliptin Phosphate
PubMed: 36034458
DOI: 10.3389/fendo.2022.897776 -
Journal of Diabetes Investigation Sep 2022The optimal therapy for latent autoimmune diabetes in adults (LADA) remains undefined. Increasing evidence has shown that sitagliptin and insulin treatment can benefit... (Meta-Analysis)
Meta-Analysis
AIMS/INTRODUCTION
The optimal therapy for latent autoimmune diabetes in adults (LADA) remains undefined. Increasing evidence has shown that sitagliptin and insulin treatment can benefit patients with LADA, but the efficacy still lacks systematic evaluation. We carried out this systematic review and meta-analysis to summarize the current data on the efficacy and safety of sitagliptin combined with insulin on LADA, providing a reliable reference for the effective therapeutic treatment of LADA patients.
MATERIALS AND METHODS
We retrieved the literature in PubMed, Cochrane Library, Embase, Web of Science and CNKI from inception to August 2021. Randomized controlled trials comparing the effects of sitagliptin plus insulin with insulin alone in LADA patients were identified. The outcome measures included parameters of glycemic control, β-cell function, body mass index and adverse events. The Review Manager 5.2 and Stata 14.0 were utilized for data analysis.
RESULTS
Eight randomized controlled trials involving 295 participants were identified. Sitagliptin and insulin treatment lowered hemoglobin A1c (weighted mean difference -0.36, 95% confidence interval -0.61 to -0.10, I = 91.6%), increased fasting C-peptide (weighted mean difference 0.08, 95% confidence interval -0.02 to 0.17, I = 88.8%) and had fewer adverse events compared with insulin alone. The inter-study heterogeneity, potential publication bias and other factors might interpret asymmetrical presentation of funnel plots. There was no significant association between sitagliptin plus insulin treatment and levels of hemoglobin A1c or fasting C-peptide, regardless of the duration of intervention and sample size.
CONCLUSIONS
Sitagliptin combined with insulin can achieve better glycemic control and improve islet β-cell function with lower incidence of hypoglycemia compared with insulin alone, which provides an effective and tolerated therapeutic regimen for LADA patients. However, further well-designed and rigorous randomized controlled trials are required to validate this benefit due to the limited methodology quality of included trials.
Topics: Adult; C-Peptide; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Latent Autoimmune Diabetes in Adults; Randomized Controlled Trials as Topic; Sitagliptin Phosphate
PubMed: 35445591
DOI: 10.1111/jdi.13814 -
Vascular Medicine (London, England) Feb 2022Abdominal aortic aneurysm (AAA) is an important vascular disease carrying significant mortality implications due to the risk of aneurysm rupture. Current management...
Abdominal aortic aneurysm (AAA) is an important vascular disease carrying significant mortality implications due to the risk of aneurysm rupture. Current management relies exclusively on surgical repair as there is no effective medical therapy. A key element of AAA pathogenesis is the chronic inflammation mediated by inflammatory cells releasing proteases, including the enzyme dipeptidyl peptidase IV (DPP-IV). This review sought to recapitulate available evidence on the involvement of DPP-IV in AAA development. Further, we assessed the experimental use of currently available DPP-IV inhibitors for AAA management in murine models. Embase, Medline, PubMed, and Web of Science databases were utilised to access the relevant studies. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A narrative synthesis approach was used. Sixty-four studies were identified from the searched databases; a final 11 were included in the analysis. DPP-IV was reported to be significantly increased in both AAA tissue and plasma of patients and correlated with AAA growth. DPP-IV inhibitors (sitagliptin, vildagliptin, alogliptin, and teneligliptin) were all shown to attenuate AAA formation in murine models by reducing monocyte differentiation, the release of reactive oxygen species (ROS), and metalloproteinases (MMP-2 and MMP-9). DPP-IV seems to play a role in AAA pathogenesis by propagating the inflammatory microenvironment. This is supported by observations of decreased AAA formation and reduction in macrophage infiltration, ROS, matrix MMPs, and interleukins following the use of DPP-IV inhibitors in murine models. There is an existing translational gap from preclinical observations to clinical trials in this important and novel mechanism of AAA pathogenesis. This prior literature highlights the need for further research on molecular targets involved in AAA formation.
Topics: Animals; Aortic Aneurysm, Abdominal; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Humans; Macrophages; Mice; Sitagliptin Phosphate
PubMed: 34392748
DOI: 10.1177/1358863X211034574 -
The Cochrane Database of Systematic... Jul 2020Kidney transplantation is the preferred management for patients with end-stage kidney disease (ESKD). However, it is often complicated by worsening or new-onset... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Kidney transplantation is the preferred management for patients with end-stage kidney disease (ESKD). However, it is often complicated by worsening or new-onset diabetes. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. This is an update of a review first published in 2017.
OBJECTIVES
To evaluate the efficacy and safety of glucose-lowering agents for treating pre-existing and new onset diabetes in people who have undergone kidney transplantation.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 16 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
All randomised controlled trials (RCTs), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and have diabetes were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Four authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI).
MAIN RESULTS
Ten studies (21 records, 603 randomised participants) were included - three additional studies (five records) since our last review. Four studies compared more intensive versus less intensive insulin therapy; two studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; one study compared DPP-4 inhibitors to insulin glargine; one study compared sodium glucose co-transporter 2 (SGLT2) inhibitors to placebo; and two studies compared glitazones and insulin to insulin therapy alone. The majority of studies had an unclear to a high risk of bias. There were no studies examining the effects of biguanides, glinides, GLP-1 agonists, or sulphonylureas. Compared to less intensive insulin therapy, it is unclear if more intensive insulin therapy has an effect on transplant or graft survival (4 studies, 301 participants: RR 1.12, 95% CI 0.32 to 3.94; I = 49%; very low certainty evidence), delayed graft function (2 studies, 153 participants: RR 0.63, 0.42 to 0.93; I = 0%; very low certainty evidence), HbA1c (1 study, 16 participants; very low certainty evidence), fasting blood glucose (1 study, 24 participants; very low certainty evidence), kidney function markers (1 study, 26 participants; very low certainty evidence), death (any cause) (3 studies, 208 participants" RR 0.68, 0.29 to 1.58; I = 0%; very low certainty evidence), hypoglycaemia (4 studies, 301 participants; very low certainty evidence) and medication discontinuation due to adverse effects (1 study, 60 participants; very low certainty evidence). Compared to placebo, it is unclear whether DPP-4 inhibitors have an effect on hypoglycaemia and medication discontinuation (2 studies, 51 participants; very low certainty evidence). However, DPP-4 inhibitors may reduce HbA1c and fasting blood glucose but not kidney function markers (1 study, 32 participants; low certainty evidence). Compared to insulin glargine, it is unclear if DPP-4 inhibitors have an effect on HbA1c, fasting blood glucose, hypoglycaemia or discontinuation due to adverse events (1 study, 45 participants; very low certainty evidence). Compared to placebo, SGLT2 inhibitors probably do not affect kidney graft survival (1 study, 44 participants; moderate certainty evidence), but may reduce HbA1c without affecting fasting blood glucose and eGFR long-term (1 study, 44 participants, low certainty evidence). SGLT2 inhibitors probably do not increase hypoglycaemia, and probably have little or no effect on medication discontinuation due to adverse events. However, all participants discontinuing SGLT2 inhibitors had urinary tract infections (1 study, 44 participants, moderate certainty evidence). Compared to insulin therapy alone, it is unclear if glitazones added to insulin have an effect on HbA1c or kidney function markers (1 study, 62 participants; very low certainty evidence). However, glitazones may make little or no difference to fasting blood glucose (2 studies, 120 participants; low certainty evidence), and medication discontinuation due to adverse events (1 study, 62 participants; low certainty evidence). No studies of DPP-4 inhibitors, or glitazones reported effects on transplant or graft survival, delayed graft function or death (any cause).
AUTHORS' CONCLUSIONS
The efficacy and safety of glucose-lowering agents in the treatment of pre-existing and new-onset diabetes in kidney transplant recipients is questionable. Evidence from existing studies examining the effect of intensive insulin therapy, DPP-4 inhibitors, SGLT inhibitors and glitazones is mostly of low to very low certainty. Appropriately blinded, larger, and higher quality RCTs are needed to evaluate and compare the safety and efficacy of contemporary glucose-lowering agents in the kidney transplant population.
Topics: Adamantane; Bias; Cause of Death; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Fasting; Glycated Hemoglobin; Graft Survival; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Kidney Transplantation; Nitriles; Pioglitazone; Postoperative Complications; Pyrrolidines; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Thiazolidinediones; Transplant Recipients; Vildagliptin
PubMed: 32803882
DOI: 10.1002/14651858.CD009966.pub3 -
Medicine Sep 2019The purpose of this study was to assess the efficacy and hypoglycemic risk of sitagliptin versus that of GLP-1 receptor agonists in the management of obese/overweight... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
The purpose of this study was to assess the efficacy and hypoglycemic risk of sitagliptin versus that of GLP-1 receptor agonists in the management of obese/overweight patients with T2DM.
METHODS
EMBASE, PubMed, Cochrane Library, and ClinicalTrials.gov were searched; randomized controlled trials comparing the efficacy of sitagliptin versus that of GLP-1 receptor agonists in obese/overweight patients with T2DM were included. The mean BMI of participants for each study was ≥30 kg/m. We conducted a meta-analysis according to the methods specified in the Cochrane Handbook for Systematic Reviews of Interventions. RevMan 5.1 software was used to perform the meta-analysis. The Cochrane Q test and I statistics were used to estimate the heterogeneity among studies. The results are expressed as the mean difference (MD) or risk ratio (RR) with 95% confidence intervals.
RESULTS
A total of 8 eligible studies were included in our meta-analysis. Compared with GLP-1 receptor agonists, sitagliptin was less effective at reducing HbA1c (0.42 [0.27, 0.56]), FPG (0.78 [0.36, 1.19]), PPG (2.61 [1.35, 3.87]), and body weight (1.42 [0.71, 2.14]). Conversely, there were no significant differences in SBP reduction (0.38 [-1.14, 1.89]), DBP reduction (-0.30 [-1.00, 0.39]), and hypoglycemic risk (1.09 [0.50, 2.35]).
CONCLUSION
For obese/overweight patients, sitagliptin may exert a less potent effect on HbA1C, FPG, PPG, and weight reduction than GLP-1 receptor agonists, but these drugs had a similar efficacy in reducing blood pressure; furthermore, there was no significant difference in hypoglycemic risk.
Topics: Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemia; Hypoglycemic Agents; Obesity; Sitagliptin Phosphate
PubMed: 31490412
DOI: 10.1097/MD.0000000000017081 -
The Cochrane Database of Systematic... Sep 2018Diabetes is the commonest cause of chronic kidney disease (CKD). Both conditions commonly co-exist. Glucometabolic changes and concurrent dialysis in diabetes and CKD... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diabetes is the commonest cause of chronic kidney disease (CKD). Both conditions commonly co-exist. Glucometabolic changes and concurrent dialysis in diabetes and CKD make glucose-lowering challenging, increasing the risk of hypoglycaemia. Glucose-lowering agents have been mainly studied in people with near-normal kidney function. It is important to characterise existing knowledge of glucose-lowering agents in CKD to guide treatment.
OBJECTIVES
To examine the efficacy and safety of insulin and other pharmacological interventions for lowering glucose levels in people with diabetes and CKD.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 12 February 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
All randomised controlled trials (RCTs) and quasi-RCTs looking at head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in people with diabetes and CKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m) were eligible.
DATA COLLECTION AND ANALYSIS
Four authors independently assessed study eligibility, risk of bias, and quality of data and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI).
MAIN RESULTS
Forty-four studies (128 records, 13,036 participants) were included. Nine studies compared sodium glucose co-transporter-2 (SGLT2) inhibitors to placebo; 13 studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; 2 studies compared glucagon-like peptide-1 (GLP-1) agonists to placebo; 8 studies compared glitazones to no glitazone treatment; 1 study compared glinide to no glinide treatment; and 4 studies compared different types, doses or modes of administration of insulin. In addition, 2 studies compared sitagliptin to glipizide; and 1 study compared each of sitagliptin to insulin, glitazars to pioglitazone, vildagliptin to sitagliptin, linagliptin to voglibose, and albiglutide to sitagliptin. Most studies had a high risk of bias due to funding and attrition bias, and an unclear risk of detection bias.Compared to placebo, SGLT2 inhibitors probably reduce HbA1c (7 studies, 1092 participants: MD -0.29%, -0.38 to -0.19 (-3.2 mmol/mol, -4.2 to -2.2); I = 0%), fasting blood glucose (FBG) (5 studies, 855 participants: MD -0.48 mmol/L, -0.78 to -0.19; I = 0%), systolic blood pressure (BP) (7 studies, 1198 participants: MD -4.68 mmHg, -6.69 to -2.68; I = 40%), diastolic BP (6 studies, 1142 participants: MD -1.72 mmHg, -2.77 to -0.66; I = 0%), heart failure (3 studies, 2519 participants: RR 0.59, 0.41 to 0.87; I = 0%), and hyperkalaemia (4 studies, 2788 participants: RR 0.58, 0.42 to 0.81; I = 0%); but probably increase genital infections (7 studies, 3086 participants: RR 2.50, 1.52 to 4.11; I = 0%), and creatinine (4 studies, 848 participants: MD 3.82 μmol/L, 1.45 to 6.19; I = 16%) (all effects of moderate certainty evidence). SGLT2 inhibitors may reduce weight (5 studies, 1029 participants: MD -1.41 kg, -1.8 to -1.02; I = 28%) and albuminuria (MD -8.14 mg/mmol creatinine, -14.51 to -1.77; I = 11%; low certainty evidence). SGLT2 inhibitors may have little or no effect on the risk of cardiovascular death, hypoglycaemia, acute kidney injury (AKI), and urinary tract infection (low certainty evidence). It is uncertain whether SGLT2 inhibitors have any effect on death, end-stage kidney disease (ESKD), hypovolaemia, fractures, diabetic ketoacidosis, or discontinuation due to adverse effects (very low certainty evidence).Compared to placebo, DPP-4 inhibitors may reduce HbA1c (7 studies, 867 participants: MD -0.62%, -0.85 to -0.39 (-6.8 mmol/mol, -9.3 to -4.3); I = 59%) but may have little or no effect on FBG (low certainty evidence). DPP-4 inhibitors probably have little or no effect on cardiovascular death (2 studies, 5897 participants: RR 0.93, 0.77 to 1.11; I = 0%) and weight (2 studies, 210 participants: MD 0.16 kg, -0.58 to 0.90; I = 29%; moderate certainty evidence). Compared to placebo, DPP-4 inhibitors may have little or no effect on heart failure, upper respiratory tract infections, and liver impairment (low certainty evidence). Compared to placebo, it is uncertain whether DPP-4 inhibitors have any effect on eGFR, hypoglycaemia, pancreatitis, pancreatic cancer, or discontinuation due to adverse effects (very low certainty evidence).Compared to placebo, GLP-1 agonists probably reduce HbA1c (7 studies, 867 participants: MD -0.53%, -1.01 to -0.06 (-5.8 mmol/mol, -11.0 to -0.7); I = 41%; moderate certainty evidence) and may reduce weight (low certainty evidence). GLP-1 agonists may have little or no effect on eGFR, hypoglycaemia, or discontinuation due to adverse effects (low certainty evidence). It is uncertain whether GLP-1 agonists reduce FBG, increase gastrointestinal symptoms, or affect the risk of pancreatitis (very low certainty evidence).Compared to placebo, it is uncertain whether glitazones have any effect on HbA1c, FBG, death, weight, and risk of hypoglycaemia (very low certainty evidence).Compared to glipizide, sitagliptin probably reduces hypoglycaemia (2 studies, 551 participants: RR 0.40, 0.23 to 0.69; I = 0%; moderate certainty evidence). Compared to glipizide, sitagliptin may have had little or no effect on HbA1c, FBG, weight, and eGFR (low certainty evidence). Compared to glipizide, it is uncertain if sitagliptin has any effect on death or discontinuation due to adverse effects (very low certainty).For types, dosages or modes of administration of insulin and other head-to-head comparisons only individual studies were available so no conclusions could be made.
AUTHORS' CONCLUSIONS
Evidence concerning the efficacy and safety of glucose-lowering agents in diabetes and CKD is limited. SGLT2 inhibitors and GLP-1 agonists are probably efficacious for glucose-lowering and DPP-4 inhibitors may be efficacious for glucose-lowering. Additionally, SGLT2 inhibitors probably reduce BP, heart failure, and hyperkalaemia but increase genital infections, and slightly increase creatinine. The safety profile for GLP-1 agonists is uncertain. No further conclusions could be made for the other classes of glucose-lowering agents including insulin. More high quality studies are required to help guide therapeutic choice for glucose-lowering in diabetes and CKD.
Topics: Cause of Death; Diabetes Mellitus; Diabetic Nephropathies; Dipeptidyl-Peptidase IV Inhibitors; Glipizide; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Sitagliptin Phosphate; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Thiazolidinediones
PubMed: 30246878
DOI: 10.1002/14651858.CD011798.pub2 -
BMJ Open Oct 2017To assess the effectiveness of sitagliptin compared to sulfonylureas as add-on to metformin in adults with type 2 diabetes mellitus from both randomised controlled... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To assess the effectiveness of sitagliptin compared to sulfonylureas as add-on to metformin in adults with type 2 diabetes mellitus from both randomised controlled trials (RCTs) and 'real-world' non-randomised studies.
METHODS AND ANALYSES
We conducted a systematic review of EMBASE, MEDLINE, CENTRAL and grey literature for RCTs and non-randomised studies. We reported outcomes relating to change in HbA1c, fasting glucose, weight, blood pressure and lipids from baseline and need for treatment change. No study investigating macrovascular and microvascular diabetes complications was found. Meta-analysis was used where studies were sufficiently homogenous.
RESULTS
Seven RCTs and five non-randomised studies were eligible for inclusion from 1335 articles retrieved. Meta-analysis of three homogenous RCTs revealed a statistically significant decrease in weight with sitagliptin when compared to sulfonylureas (weighted mean difference (WMD) -2.05 kg; 95% CI -2.38 to -1.71); however, a similar change from baseline in HbA1c (WMD 0.05; 95% CI -0.03 to 0.12), fasting glucose (WMD 0.11; 95% CI -0.08 to -0.29), blood pressure, lipids and the proportion achieving HbA1c <7% by study end (OR 0.98; 95% CI 0.85 to 1.13) was observed.Non-randomised studies identified consisted of four prospective and one retrospective cohort study. Three of these five studies were of moderate/high quality, and results though less precise suggested similar real-world comparative glycaemic and weight effectiveness for both treatments. Data from two cohort studies suggested that treatment change (HR 0.65; 95% CI 0.57 to 0.73) and insulin initiation (HR 0.76; 95% CI 0.65 to 0.90) were less likely among those prescribed sitagliptin; however, inadequate reporting of HbA1c at time of treatment change made interpreting results challenging.
CONCLUSION
Sitagliptin users experienced modest weight loss compared to gain with sulfonylureas; however, this difference was around 2 kg, which may not be of major clinical significance for most individuals. Similar change was observed across most other effectiveness outcomes reported. Further studies are needed to address longer-term effectiveness outcomes for sitagliptin compared to sulfonylureas as add-on to metformin.
PROSPERO REGISTRATION NUMBER
CRD42016033983.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Metformin; Middle Aged; Outcome Assessment, Health Care; Sitagliptin Phosphate; Sulfonylurea Compounds; Weight Loss; Young Adult
PubMed: 29084794
DOI: 10.1136/bmjopen-2017-017260