1.
Efficacy and safety of liraglutide in type 2 diabetes mellitus patients complicated with coronary artery disease: A systematic review and meta-analysis of randomized controlled trials.
Wang, L, Xin, Q, Wang, Y, Chen, Z, Yuan, R, Miao, Y, Zhang, G, Cong, W
Pharmacological research. 2021;:105765
Abstract
To evaluate the efficacy and safety of liraglutide in patients with Type 2 Diabetes Mellitus (T2DM) complicated with Coronary Artery Disease (CAD), we searched PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese VIP Information (VIP), Wanfang Database and Chinese Biomedical Literature database (CBM) for relevant randomized controlled trials (RCTs) from inception to 7 October 2020. A total of 18 RCTs including 1557 patients with T2DM complicated with CAD were included. Meta-analysis revealed liraglutide reduced hemoglobin A1c (HbA1c) (WMD = -0.67; 95% CI[-0.94 to -0.39]; P < 0.00001), fasting plasma glucose (FPG) (WMD = -0.80; 95% CI[-1.06 to -0.54]; P < 0.00001) and 2 h plasma glucose (2hPG) (WMD = -1.64; 95% CI[-2.12 to -1.16]; P<0.00001); improved left ventricular ejection fraction(LVEF) (WMD = 4.79; 95% CI[4.08-5.51]; P < 0.00001), left ventricular end-diastolic diameter (LVEDD) (WMD = -5.70; 95% CI[-6.67 to -4.72]; P<0.00001), E/A (WMD = 0.13; 95% CI[0.11-0.14]; P < 0.00001) and left ventricular posterior wall thickness (LVPWT) (WMD = -1.86; 95% CI[-2.16 to -1.55]; P < 0.00001); reduced total cholesterol (TC) (WMD = -0.48; 95% CI[-0.56 to -0.39]; P < 0.00001), triglycerides (TG) (WMD = -0.42; 95% CI[-0.59 to -0.26]; P < 0.00001), low-density lipoprotein cholesterol (LDL-C) (WMD = -0.41; 95% CI[-0.55 to -0.26]; P < 0.00001), and increased high-density lipoprotein cholesterol (HDL-C) (WMD = -0.19; 95% CI[0.13-0.24]; P = 0.0005). As for safety assessment, liraglutide did not increase the incidence of hypoglycemia (OR = 0.75, 95% CI[0.32-1.77], P = 0.51) and gastrointestinal (OR = 1.15, 95% CI[0.72-1.85], P = 0.55) events. Consequently, liraglutide had favorable effects on blood glucose, cardiac function, lipid profile and an acceptable safety profile.
2.
Liraglutide as Adjunct to Insulin Treatment in Patients with Type 1 Diabetes: A Systematic Review and Meta-analysis.
Dimitrios, P, Michael, D, Vasilios, K, Konstantinos, S, Konstantinos, I, Ioanna, Z, Konstantinos, P, Spyridon, B, Asterios, K
Current diabetes reviews. 2020;(4):313-326
Abstract
BACKGROUND A few Randomized Controlled Trials (RCTs) have evaluated the use of liraglutide in Type 1 Diabetes (T1D). Through the present systematic review and meta-analysis, we aim at critically appraising and summarizing those RCTs, providing precise effect estimates. METHODS We searched major databases and grey literature from their inception to October 2018, for RCTs with a duration ≥ 12 weeks, comparing liraglutide with placebo or any other comparator as adjunct to insulin in patients with T1D, investigating major efficacy and safety endpoints. This review is reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. RESULTS We included 5 trials with 2,445 randomized participants. Liraglutide provided modest reductions in HbA1c, with liraglutide 1.8 mg producing the greatest decrease (MD = -0.24%, 95% CI -0.32 to -0.16, I2=0%). Significant weight reduction, up to 4.87 kg with liraglutide 1.8 mg was also observed (95% CI -5.31 to -4.43, I2=0%). Decrease in total daily insulin dose, primarily driven by a decrease in bolus insulin requirements, was demonstrated. Liraglutide decreased non-significantly the odds for severe hypoglycemia (OR=0.80, 95% CI 0.57-1.14, I2=0%), while it increased significantly the odds for gastrointestinal adverse events (for nausea, OR=4.70, 95% CI 3.68-6.00, I2=37%, and for vomiting, OR=2.50, 95% CI 1.54-4.72, I2=27%). A significant increase in heart rate was also demonstrated. No association with diabetic ketoacidosis or malignancies was identified. CONCLUSION In patients with T1D, liraglutide might prove be an adjunct to insulin, improving glycemic control, inducing body weight loss and decreasing exogenous insulin requirements and severe hypoglycemia.
3.
A meta-analysis comparing clinical effects of short- or long-acting GLP-1 receptor agonists versus insulin treatment from head-to-head studies in type 2 diabetic patients.
Abd El Aziz, MS, Kahle, M, Meier, JJ, Nauck, MA
Diabetes, obesity & metabolism. 2017;(2):216-227
Abstract
AIMS: To study differences in clinical outcomes between initiating glucagon-like peptide-1 receptor agonist (GLP-1 RAs) vs insulin treatment in patients with type 2 diabetes treated with oral glucose-lowering medications (OGLM). METHODS Prospective, randomized trials comparing GLP-1 RA and insulin treatment head-to-head as add-on to OGLM were identified (PubMed). Differences from baseline values were compared for HbA1c, fasting plasma glucose, bodyweight, blood pressure, heartrate and lipoproteins. Proportions of patients reporting hypoglycaemic episodes were compared. RESULTS Of 712 publications identified, 23 describing 19 clinical trials were included in the meta-analysis. Compared to insulin, GLP-1 RAs reduced HbA1c more effectively (Δ -.12%, P < .0001). Basal insulin was more effective in reducing fasting plasma glucose (Δ -1.8 mmol/L, P < .0001). GLP-1 RAs reduced bodyweight more effectively (Δ -3.71 kg; P < .0001). The proportion of patients experiencing hypoglycaemic episodes was 34% lower with GLP-1 RAs ( P < .0001), with a similar trend for severe hypoglycaemia. Systolic blood pressure was lower and heartrate was higher with GLP-1 RAs ( P < .0001). Triglycerides and LDL cholesterol were significantly lower with GLP-1 RAs. Long-acting GLP-1 RAs were better than short-acting GLP-1 RAs in reducing HbA1c and fasting glucose, but were similar regarding bodyweight. CONCLUSIONS Slightly better glycaemic control can be achieved by adding GLP-1 RAs to OGLM as compared to insulin treatment, with added benefits regarding bodyweight, hypoglycaemia, blood pressure and lipoproteins. These differences are in contrast to the fact that insulin is prescribed far more often than GLP-1 RAs.
4.
Impact of diabetes duration on achieved reductions in glycated haemoglobin, fasting plasma glucose and body weight with liraglutide treatment for up to 28 weeks: a meta-analysis of seven phase III trials.
Seufert, J, Bailey, T, Barkholt Christensen, S, Nauck, MA
Diabetes, obesity & metabolism. 2016;(7):721-4
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Abstract
This meta-analysis of seven randomized, placebo-controlled studies (total 3222 patients) evaluated whether type 2 diabetes (T2D) duration affects the changes in blood glucose control and body weight that can be achieved with liraglutide and placebo. With liraglutide 1.2 mg, shorter diabetes duration was associated with a significantly greater, but clinically non-relevant, difference in glycated haemoglobin (HbA1c) reduction (p < 0.05), i.e. a 0.18% (1.96 mmol/mol) reduction in HbA1c per 10 years shorter diabetes duration. With liraglutide 1.8 mg, shorter diabetes duration was associated with a small but statistically significant trend for greater fasting plasma glucose (FPG) reduction (p < 0.05), i.e. a 0.38 mmol/l reduction in FPG per 10 years shorter diabetes duration. Neither the liraglutide 1.8 mg nor placebo results showed a significant association between HbA1c and diabetes duration and neither the liraglutide 1.2 mg nor placebo results showed a significant association between FPG and diabetes duration. Likewise, neither liraglutide nor placebo showed a significant association between change in weight and diabetes duration. These results suggest diabetes duration has a clinically negligible effect on achievable blood glucose control and weight outcomes with liraglutide and placebo in patients with T2D.