1.
Effects of Basal Insulin on Lipid Profile Compared to Other Classes of Antihyperglycemic Agents in Type 2 Diabetic Patients.
Rigato, M, Avogaro, A, Vigili de Kreutzenberg, S, Fadini, GP
The Journal of clinical endocrinology and metabolism. 2020;(7)
Abstract
OBJECTIVE The lipid profile represents a driver of cardiovascular risk in type 2 diabetes. The effect of chronic insulin therapy on cholesterol levels is unclear. We aim to evaluate the effect of basal insulin on lipid profile compared to other classes of antihyperglycemic agents in type 2 diabetic patients. DESIGN We performed a meta-analysis of randomized controlled trials reporting changes of lipid parameters in type 2 diabetic patients randomly assigned to basal insulin or other classes of anti-hyperglycemic agents. RESULTS The levels of total (TC) and low-density lipoprotein cholesterol (LDL-C) appeared to be significantly reduced by therapies with glucagon-like peptide-1 receptor agonists (GLP-1RA) in comparison to basal insulin (mean difference [MD] -3.80; 95% CI [-6.30 to -1.30] mg/dL, P < .001 and -4.17; 95% CI [-6.04 to -2.30] mg/dL, P < .0001), whereas no difference was detected between basal insulin and dipeptidyl peptidase-4 inhibitors (DPP4-I) or standard therapy (sulfonylurea ± metformin). Thiazolidinediones (TZD) produced a significant improvement in high-density lipoprotein cholesterol (HDL-C) (MD 3.55; 95% CI: 0.55 to 6.56 mg/dL, P = .02) but were associated with an increase in TC and LDL-C (MD 16.20; 95% CI: 9.09 to 23.31 mg/dL, P < .001 and 5.19: 95% CI: -3.00 to 13.39 mg/dL, P = .21). Basal insulin was superior to standard therapy in triglyceride reduction (MD 3.8; 95% CI: 0.99 to 6.63 mg/dL, P = .008). CONCLUSIONS GLP-1RA were superior to basal insulin in the control of TC and LDL-C. Basal insulin effectively reduced serum triglycerides. TZD led to improvement in HDL-C. DPP4-I and standard therapy did not have any significant effect on lipid levels.
2.
Sodium-Glucose Co-Transporter 2 Inhibitors Compared with Sulfonylureas in Patients with Type 2 Diabetes Inadequately Controlled on Metformin: A Meta-Analysis of Randomized Controlled Trials.
Chen, Z, Li, G
Clinical drug investigation. 2019;(6):521-531
Abstract
BACKGROUND AND OBJECTIVE When metformin is insufficient for patients with type 2 diabetes mellitus (T2DM), the optimal adjunctive therapy is unclear. This meta-analysis was to compare the efficacy and safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors with sulfonylureas (SUs) as second-line therapy in patients with T2DM inadequately controlled on metformin. METHODS We systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for randomized controlled trials comparing SGLT2 inhibitors with SUs as add-on to metformin. Our primary endpoints were glycemic control, hypoglycemia, and change in weight. We assessed pooled data using a random-effects model. RESULTS Five trials involving 4300 participants were included in our meta-analysis. Compared with SUs, SGLT2 inhibitors led to no significant reduction in changes in HbA1c (mean difference [MD] - 0.06; 95% confidence interval [CI] [- 0.12, 0.08]), but less hypoglycemia as add-on to metformin (odds ratio [OR] 0.12; 95% CI [0.07, 0.21]). SGLT2 inhibitors led to a reduction in weight by about 3.5 kg; however, SUs caused a gain in weight by about 1 kg (MD - 4.39; 95% CI [- 4.64, - 4.14]). SGLT2 inhibitors also showed a reduction in blood pressure, but increased the incidence of genital tract infections compared with SUs. Interestingly, subgroup analysis by duration of interventions showed that reduction of HbA1c from baseline was similar between the two groups at 12-52 weeks, but SGLT2 inhibitors led to a greater reduction in HbA1c at 104-208 weeks. CONCLUSIONS Despite similar glycemic efficacy in a relatively short term, SGLT2 inhibitors are more effective in the longer term than SUs as add-on to metformin. In addition, SGLT2 inhibitors produce less hypoglycemic events and lead to greater reductions in weight and blood pressure compared with SUs.
3.
Comparison of antidiabetic drugs added to sulfonylurea monotherapy in patients with type 2 diabetes mellitus: A network meta-analysis.
Qian, D, Zhang, T, Tan, X, Zheng, P, Liang, Z, Xie, J, Jiang, J, Situ, B
PloS one. 2018;(8):e0202563
Abstract
AIMS: This study aimed to investigate the efficacy and safety of dual therapy comprising sulfonylurea (SU) plus antidiabetic drugs for the treatment of type 2 diabetes mellitus (T2DM). METHODS We searched the PubMed, Cochrane library, and Embase databases for randomized clinical trials (≥24 weeks) published up to December 28, 2017. Subsequently, we conducted pairwise and network meta-analyses to calculate the odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) of the outcomes. RESULTS The final analyses included 24 trials with a total of 10,032 patients. Compared with placebo, all treatment regimens were associated with a significantly higher risk of hypoglycemia, except the combinations of SU plus sodium-glucose co-transporter-2 inhibitor (SGLT-2i) [OR, 1.35 (95% CI: 0.81 to 2.25)] or alpha-glucosidase inhibitor (AGI) [OR, 1.16 (95% CI: 0.55 to 2.44)]. Notably, the combination of SU plus glucagon-like peptide-1 receptor agonist (GLP-1RA) was associated with the most significant increase in the risk of hypoglycemia. Furthermore, all SU-based combination regimens reduced the glycated hemoglobin (HbA1c) and fasting plasma glucose levels (FPG). However, only combinations containing SGLT-2i [MD, -1.00 kg (95% CI: -1.73 to -0.27)] and GLP-1RA [MD, -0.56 kg (95% CI: -1.10 to -0.02)] led to weight loss. CONCLUSIONS Our findings highlight the importance of considering the risk of hypoglycemia when selecting antidiabetic drugs to be administered concomitantly with SU. Although all classes of antidiabetic drugs improved glucose control when administered in combination with SU, SGLT-2i might be the best option with respect to factors such as hypoglycemia and body weight.