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Daru : Journal of Faculty of Pharmacy,... Oct 2017Diabetes is one of the most common chronic and costly diseases worldwide and type 2 diabetes is the most common type which accounts for about 90% of cases with diabetes.... (Comparative Study)
Comparative Study Review
BACKGROUND
Diabetes is one of the most common chronic and costly diseases worldwide and type 2 diabetes is the most common type which accounts for about 90% of cases with diabetes. New medication-therapy regimens such as those containing linagliptin alone or in combination with other medications (within the category of DDP-4 inhibitors) must be evaluated in terms of efficacy and compared with other currently used drugs and then enter the medication list of the country. Hence, this study aimed to compare the clinical efficacy of the two drugs, i.e. linagliptin and sitagliptin, in patients with type 2 diabetes.
METHODS
A systematic review was conducted to identify all clinical trials published by 2015 which compared the two drugs in patients with type 2 diabetes. Using keywords such as "linagliptin", "type 2 diabetes mellitus", "sitagliptin" and related combinations, we searched databases including Scopus, PubMed, and Web of Science. The quality of the selected studies was evaluated using the Jadad score. Considering primary and secondary outcomes extracted from the reviewed studies, a network meta-analysis was used to conduct a systematic comparison between the two studied drugs.
RESULTS
This network meta-analysis included 32 studies (Linagliptin vs PLB: n = 8, Sitagliptin vs PLB: n = 13, Linagliptin + MET vs PLB + MET: n = 4, and Sitagliptin + MET vs PLB + MET: n = 7) and a total of 13,747 patients. The results showed no significant difference between linagliptin and sitagliptin in terms of key efficacy and safety outcomes such as HbA1c changes from baseline, body weight change from baseline, percentage of patients achieving HbA1c <7, and percentage of patients experiencing hypoglycemic events (p > 0.05). The results showed that the efficacy of the two drug regimens was the same.
CONCLUSIONS
Based on the results, there was no significant difference between the two drugs, i.e. linagliptin and sitagliptin, in terms of efficacy; in other words, the efficacy of the two drugs was the same. Therefore, the use of these two drugs depends on their availability and cost. Graphical abstract of the network meta-analysis performed to evaluate the alternatives under the study.
Topics: Aged; Aged, 80 and over; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Linagliptin; Male; Middle Aged; Network Meta-Analysis; Sitagliptin Phosphate; Treatment Outcome
PubMed: 29070077
DOI: 10.1186/s40199-017-0189-6 -
Clinical Therapeutics Dec 2014Although recent reports suggest an association between saxagliptin and an increased risk of admissions for heart failure, it is not clear whether dipeptidyl peptidase IV... (Review)
Review
PURPOSE
Although recent reports suggest an association between saxagliptin and an increased risk of admissions for heart failure, it is not clear whether dipeptidyl peptidase IV (DPP-IV) inhibition contributes to heart failure in high-risk patients. The purpose of this research is to understand heart failure risk among high-risk patients with type 2 diabetes.
METHODS
This is a systematic review of data published in full papers and abstract form using the terms DPP-IV inhibitors and heart failure published since October 2013. Data from insurance and hospital databases were combined with those from multiple published trials, including the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial; Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care (EXAMINE), and Vildagliptin in Ventricular Dysfunction Diabetes (VIVIDD) trial as well as pooled analyses of linagliptin and saxagliptin placebo-controlled trials to examine heart failure among patients represented in those datasets.
FINDINGS
A meta-analysis of the 9 datasets showed an increase in heart failure with dipeptidyl peptidase IV inhibitors of 15% (P = 0.017). There was no statistical heterogeneity, nor was there a statistical difference between cohort studies and randomized, controlled trials (P = 0.3), even though cohort studies alone were not significant (relative risk: 1.1; P = 0.32). Removing SAVOR-TIMI 53 data produced an insignificant increase in heart failure of 12% (P = 0.09) in the rest of the studies. In the randomized, controlled trials, the increased risk was 24% (P = 0.002). There was no statistical difference between those studies with and without baseline cardiovascular disease (P = 0.58), although the cardiovascular disease studies were borderline significant (P = 0.06). There was no publication bias.
IMPLICATIONS
There are data from studies using sitagliptin, saxagliptin, and alogliptin showing that these agents may increase the risk of hospitalization for heart failure. More data are required for a definitive conclusion.
Topics: Adamantane; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Heart Failure; Hospitalization; Humans; Nitriles; Piperidines; Pyrrolidines; Sitagliptin Phosphate; Uracil; Vildagliptin
PubMed: 25453730
DOI: 10.1016/j.clinthera.2014.10.009 -
Scientific Reports Jan 2016A meta-analysis was conducted to assess the clinical efficacy and safety of dulaglutide in patients with type 2 diabetes mellitus (T2DM). Medline, Embase, Cochrane... (Meta-Analysis)
Meta-Analysis Review
A meta-analysis was conducted to assess the clinical efficacy and safety of dulaglutide in patients with type 2 diabetes mellitus (T2DM). Medline, Embase, Cochrane Library and www. clinicaltrials. gov (up to February 15(th), 2015) were searched. Randomized controlled trials comparing dulaglutide to other drugs for T2DM were collected. Twelve RCTs were included, and the overall bias was low. As the monotherapy, compared with control (placebo, metformin and liraglutide), dulaglutide resulted in a significant reduction in HbA1c (WMD, -0.68%; 95% CI, -0.95 to -0.40), FPG (WMD, -0.90 mmol/L; 95% CI, -1.28 to -0.52), a similar risk of hypoglycemia (7.8% vs. 10.6%), less body weight loss (WMD, 0.51 kg; 95% CI, 0.27 to 0.75). As an add-on intervention with oral antihyperglycemic medication (OAM) and insulin, compared with control (placebo, sitagliptin, exenatide, liraglutide and glargine), dulaglutide lowered HbA1c (WMD, -0.51%; 95% CI, -0.68 to -0.35) and body weight significantly (WMD, -1.30 kg, 95% CI, -1.85 to -1.02) notably, and elicited a similar reduction in FPG (WMD, -0.19 mmol/L; 95% CI, -1.20 to 0.82), an similar incidence of hypoglycemia (24.5% vs. 24.5%). This meta-analysis revealed the use of dulaglutide as a monotherapy or an add-on to OAM and lispro appeared to be effective and safe for adults with T2DM.
Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Insulin; Insulin Glargine; Liraglutide; Metformin; Patient Safety; Peptides; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Sitagliptin Phosphate; Treatment Outcome; Venoms
PubMed: 26742577
DOI: 10.1038/srep18904 -
Hormone and Metabolic Research =... Jul 2020Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease. However, the treatment is limited. The aim of this meta-analysis... (Meta-Analysis)
Meta-Analysis
Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease. However, the treatment is limited. The aim of this meta-analysis was to evaluate the effects and safety of sitagliptin, a selective inhibitor of dipeptidyl peptidase-4 (DPP-4I), in treating NAFLD. Studies were sourced from electronic databases including PubMed, CENTRAL (Cochrane Controlled Trials Register), Embase, Medline, Web of Science, Clinical Trials, and CNKI to identify all randomized controlled clinical trials (RCTs) and non-RCTs in adult patients with NAFLD. Key outcomes were changes in serum levels of liver enzymes and improvement in hepatic histology and fat content measured by imaging or liver biopsy. Stata14.0 and RevMan5.3 were used for the meta-analysis. Seven studies with 269 NAFLD patients were included. Compared to the control group, sitagliptin treatment improved serum gamma-glutamyl transpeptidase (GGT) levels in the RCT subgroup (SMD = 0.79, 95% CI: 0.01-1.58). However, there was no significant improvement in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels following sitagliptin treatment. Four of the included studies performed liver imaging, but sitagliptin treatment did not result in a significant reduction in liver fat content. Only five participants developed sitagliptin-related gastrointestinal discomfort. Our study suggests that sitagliptin effects individuals with NAFLD by improving serum GGT. Although sitagliptin is safe and well tolerated in NAFLD patients, it exerts no beneficial effects on liver transaminase and liver fat content in these patients.
Topics: Aged; Clinical Trials as Topic; Female; Humans; Hypoglycemic Agents; Liver; Liver Function Tests; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Sitagliptin Phosphate; Treatment Outcome
PubMed: 32559768
DOI: 10.1055/a-1186-0841 -
PloS One 2014Incretin-based therapies which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are recommended by several... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Incretin-based therapies which include glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are recommended by several practice guidelines as second-line agents for add-on therapy to metformin in patients with type 2 diabetes (T2DM) who do not achieve glycemic control with metformin plus lifestyle interventions alone. The purpose of this study is to perform a systematic review with meta-analysis of existing head to head studies to compare the efficacy and safety of GLP-1 analogues with DPP-4 inhibitors.
METHODS
We performed a systematic review and meta-analysis of head-to-head studies to compare GLP-1 analogues with DPP-4 inhibitors in the management of type 2 diabetes. A random effects model was selected to perform the meta-analyses, results were expressed as weighted mean differences for continuous outcomes and relative risks for dichotomous outcomes, both with 95% confidence intervals, and with I2 values and P values as markers of heterogeneity.
RESULTS
Four head-to-head randomized controlled studies with 1755 patients were included. Compared to sitagliptin, GLP-1 analogues are more effective in reducing HbA1C (weight mean difference -0.41%, 95% CI -0.51 to -0.31) and body weight (weight mean difference -1.55 kg, 95% CI -1.98 to -1.12). Conversely, GLP-1 analogues are associated with a higher incidence of gastrointestinal adverse events compared to sitagliptin: nausea (relative risk 3.14, 95% CI 2.15 to 4.59), vomiting (relative risk 2.60, 95% CI 1.48 to 4.56), diarrhea (relative risk 1.82, 95% CI 1.24 to 2.69), and constipation (relative risk 2.50, 95% CI 1.33 to 4.70).
CONCLUSIONS
The result of this meta-analysis demonstrates that compared to sitagliptin, GLP-1 analogues are more effective for glycemic control and weight loss, but have similar efficacy in reducing blood pressure and lipid parameters, however, GLP-1 analogues are associated with a higher incidence of gastrointestinal adverse events and a similar incidence of hypoglycemia compared to sitagliptin.
Topics: Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Fasting; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Lipids; Pyrazines; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; Treatment Outcome; Triazoles
PubMed: 25089625
DOI: 10.1371/journal.pone.0103798 -
Drug Research Nov 2021Sitagliptin is known as an antidiabetic agent inhibiting the dipeptidyl peptidase-4. Although sitagliptin may influence weight, controversial results have been reported,... (Meta-Analysis)
Meta-Analysis
Effects of Sitagliptin as Monotherapy and Add-On to Metformin on Weight Loss among Overweight and Obese Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.
BACKGROUND
Sitagliptin is known as an antidiabetic agent inhibiting the dipeptidyl peptidase-4. Although sitagliptin may influence weight, controversial results have been reported, and there is no general agreement on this issue. Therefore, this study assessed the effect of sitagliptin as monotherapy and add-on therapy to metformin on weight reduction in overweight or obese cases with type 2 diabetes.
METHODS
We reviewed the following databases to identify all relevant papers published until 1st April 2021: Web of Science, MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials Cochrane Library, and Google Scholar. The research included all clinical trials investigating the effect of sitagliptin in obese or overweight adult patients with type 2 diabetes without any language restriction.
RESULTS
In total, eighteen randomized controlled trials with 2009 participants were included in our meta-analysis. Results showed supplementation of sitagliptin has led to weight loss for sitagliptin treated (MD -0.99; 95% CI; (-1.87, -0.12); p=0.026)) and sitagliptin+metformin treated groups (MD -1.09; 95% CI; (-1.69, -0.49); p<0.001)). Also, the intervention has influenced body mass index in sitagliptin treated (MD -0.23; 95% CI; (-0.45, 0.02); p=0.033)) and sitagliptin+metformin treated groups (MD -0.52; 95% CI; (-0.96, 0.08); p=0.020)) comparing to placebo.
CONCLUSION
Our results demonstrated that sitagliptin administration with or without metformin might reduce the body weight and body mass index if these drugs are taken for more than 6 months.
Topics: Adult; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Metformin; Obesity; Overweight; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; Weight Loss
PubMed: 34388848
DOI: 10.1055/a-1555-2797 -
Journal of Cardiovascular Medicine... May 2022Lipid abnormalities often occur in patients with diabetes mellitus and the coexistence of diabetes mellitus and dyslipidaemia will increase the risk of cardiovascular... (Meta-Analysis)
Meta-Analysis
AIM
Lipid abnormalities often occur in patients with diabetes mellitus and the coexistence of diabetes mellitus and dyslipidaemia will increase the risk of cardiovascular diseases. However, the specific effects of sitagliptin on lipid control remain elusive in diabetic patients. The aim of this meta-analysis is to investigate the effects of sitagliptin alone or with other antidiabetic agents on serum lipid control.
METHODS
PubMed, Cochrane Library, Embase and the ClinicalTrials.gov website were systematically searched from 2006 (the first year that sitagliptin entered market) to 16 January 2021. Eligible studies were randomized clinical trials (RCTs) of sitagliptin including outcomes of serum total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein cholesterol (LDL-C).
RESULTS
A total of 14 RCTs with 2654 patients were identified. Treatment with sitagliptin alone or in combination with other antidiabetic agents significantly reduced serum TC [mean difference (MD) = -5.52 95% confidence interval (95% CI), -7.88 to -3.15; P < 0.00001] and LDL-C (MD = -0.07; 95% CI, -0.14 to 0.00; P < 0.00001) in patients with type 2 diabetes. No statistical significances were found in serum triglycerides (MD = 1.53; 95% CI, -8.22 to 11.28; P = 0.76) or HDL-C (MD = 0.65; 95% CI, -1.59 to 0.29; P = 0.18). Subgroup analyses suggest that sitagliptin can significantly decrease serum LDL-C, TC and triglyceride levels compared with placebo alone, and no statistical significance was found in comparison with the serum HDLC levels.
CONCLUSION
Sitagliptin alone or in combination with other antidiabetic agents significantly reduces serum TC and LDL-C in patients with type 2 diabetes mellitus, while no significant difference was observed in serum triglycerides or HDL-C.
Topics: Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Sitagliptin Phosphate; Triglycerides
PubMed: 35486682
DOI: 10.2459/JCM.0000000000001270 -
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 -
Diabetes, Obesity & Metabolism Jul 2015To determine which non-insulin glucose-lowering treatment regimens are most appropriate in people with type 2 diabetes who choose to fast during Ramadan. (Meta-Analysis)
Meta-Analysis Review
Safety and effectiveness of non-insulin glucose-lowering agents in the treatment of people with type 2 diabetes who observe Ramadan: a systematic review and meta-analysis.
AIM
To determine which non-insulin glucose-lowering treatment regimens are most appropriate in people with type 2 diabetes who choose to fast during Ramadan.
METHODS
Electronic databases were searched for randomized controlled trials (RCTs) and observational studies that compared non-insulin glucose-lowering agents in people with type 2 diabetes fasting during Ramadan. Those studies which reported hypoglycaemia, weight and glycated haemoglobin (HbA1c) change were included. Data were pooled using random effects models.
RESULTS
A total of 16 studies were included: 9 RCTs and 7 observational studies. There was evidence that dipeptidyl peptidase-4 (DPP-4) inhibitors led to fewer hypoglycaemic events compared with sulphonylureas. Sitagliptin significantly reduced the number of patients with ≥1 hypoglycaemic episodes during Ramadan [risk ratio (RR) 0.48, 95% confidence interval (CI) 0.36, 0.64; p > 0.0001]. This was not replicated in the RCTs of vildagliptin, but a significant reduction was found in the observational studies (RR 0.28, 95% CI 0.10, 0.75; p = 0.01) with high heterogeneity (I(2) = 86.7%). Significant reductions in HbA1c and weight were seen in the observational studies of vildagliptin versus sulphonylureas. The use of liraglutide led to significant weight loss (-1.81 kg, 95% CI -2.91, -0.71; p = 0.001) compared with sulphonylureas. Pioglitazone significantly increased weight compared with placebo (3.48 kg, 95% CI 2.82, 4.14; p < 0.0001).
CONCLUSIONS
The analysis supports the use of DPP-4 inhibitors during Ramadan rather than sulphonylureas for reduction in hypoglycaemia without a cost to diabetes control and weight. The glucagon-like peptide (GLP)-1 agonist liraglutide provides clinical benefits, but more studies are required. RCTs of DPP-4 inhibitors compared with GLP-1 agonists and novel therapies including the sodium-glucose co-transporter 2 and α-glucosidase inhibitors are needed to inform evidence-based guidelines.
Topics: Adamantane; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Holidays; Humans; Hypoglycemia; Hypoglycemic Agents; Islam; Liraglutide; Nitriles; Observational Studies as Topic; Pioglitazone; Pyrrolidines; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; Sulfonylurea Compounds; Thiazolidinediones; Vildagliptin; Weight Loss
PubMed: 25777247
DOI: 10.1111/dom.12462 -
Journal of Diabetes and Its... Sep 2017Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes mellitus. There are also reports of an effect of these drugs in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes mellitus. There are also reports of an effect of these drugs in reducing inflammation through inhibition of tumor necrosis factor-α (TNF-α) that is an important mediator for several inflammatory processes. The present systematic review and meta-analysis were performed to evaluate the effect of DPP-4 inhibitors on circulating TNF-α levels in T2DM patients.
METHODS
A systematic review and a meta-analysis were undertaken on all controlled trials of DPP-4 inhibitors that included measurement of TNF-α. The search included PubMed-Medline, Scopus, ISI Web of Knowledge and Google Scholar databases. Quantitative data synthesis was performed using a random-effects model, with standardized mean difference (SMD) and 95% confidence interval (CI) as summary statistics. Meta-regression and leave-one-out sensitivity analysis were performed to assess the modifiers of treatment response.
RESULTS
Eight eligible articles (6 with sitagliptin and 2 with vildagliptin) comprising 9 treatment arms were selected for this meta-analysis. Meta-analysis suggested a significant reduction of circulating TNF-α concentrations following treatment with DPP-4 inhibitors (SMD: -1.84, 95% CI: -2.88, -0.80, p=0.001). The effect size was robust in the sensitivity analysis and not mainly driven by a single study. A subgroup analysis did not suggest any significant difference between the TNF-α-lowering activity of sitagliptin (SMD: -1.49, 95% CI: -2.89, -0.10) and vildagliptin (SMD: -2.80, 95% CI: -4.98, -0.61) (p=0.326).
CONCLUSION
This meta-analysis of the 8 available controlled trials showed that DPP-4 inhibition in patients with type 2 diabetes mellitus was associated with significant reductions in plasma TNF-α levels with no apparent difference between sitagliptin and vildagliptin.
Topics: Adamantane; Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hypoglycemic Agents; Nitriles; Pyrrolidines; Sitagliptin Phosphate; Tumor Necrosis Factor-alpha; Vildagliptin
PubMed: 28647512
DOI: 10.1016/j.jdiacomp.2017.05.016