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Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.
Palmer, SC, Tendal, B, Mustafa, RA, Vandvik, PO, Li, S, Hao, Q, Tunnicliffe, D, Ruospo, M, Natale, P, Saglimbene, V, et al
BMJ (Clinical research ed.). 2021;:m4573
Abstract
OBJECTIVE To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. DESIGN Network meta-analysis. DATA SOURCES Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. MAIN OUTCOME MEASURES Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. RESULTS 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 3 to 40 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. CONCLUSIONS In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with some differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019153180.
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Effects of Sodium-glucose Cotransporter 2 Inhibitor Monotherapy on Weight Changes in Patients With Type 2 Diabetes Mellitus: a Bayesian Network Meta-analysis.
Wang, H, Yang, J, Chen, X, Qiu, F, Li, J
Clinical therapeutics. 2019;(2):322-334.e11
Abstract
PURPOSE The aim of this study was to systematically evaluate the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor monotherapy on the weight of patients with type 2 diabetes mellitus (T2DM) and to compare different SGLT2 inhibitors with other oral glucose-lowering medications. METHODS PubMed, EMBASE, Cochrane Library, and the ClinicalTrials.gov Web site were searched for relevant randomized controlled trials. Patients with T2DM in the included studies were administered SGLT2 inhibitor monotherapy for at least 12 weeks. The primary outcome was the change in weight from baseline; the secondary outcome was the proportion of patients achieving a weight reduction ≥5%. A pairwise meta-analysis using the DerSimonian-Laird random effects model and a network meta-analysis with Bayesian Markov chain Monte Carlo random effects models were performed. FINDINGS A total of 29 randomized controlled trials (11,999 patients) with a low risk of bias were identified. The results showed that the mean weight loss ranged from -2.26 kg (95% credible interval [CrI], -2.71 to -1.76) with canagliflozin 300 mg to -0.79 kg (95% CrI, -1.54 to -0.05) with ipragliflozin 25 mg compared with metformin. Compared with linagliptin and sitagliptin, the mean weight loss ranged from -3.17 kg (95% CrI, -3.67 to -2.57) with canagliflozin 300 mg to -0.93 kg (95% CrI, -1.92 to 0.05) with ipragliflozin 25 mg. Canagliflozin 300 mg reduced weight to a greater extent than the other SGLT2 inhibitors, with a probability of 99.44%. SGLT2 inhibitors also improved the proportions of patients achieving ≥5% weight loss. The effect of SGLT2 inhibitors on weight reduction was associated with dosage. IMPLICATIONS Available evidence from randomized controlled trials suggests that SGLT2 inhibitor monotherapy exerts more beneficial effects on weight reduction than both metformin and dipeptidyl peptidase 4 inhibitors. The weight reduction effect of 300 mg canagliflozin is greater than that of most other SGLT2 inhibitors. More types of SGLT2 inhibitors in a head-to-head trial, as well as a comparison between SGLT2 inhibitors and glucagon-like peptide 1 receptor agonists, will be involved in our further research. International Prospective Register of Systematic Reviews: CRD42018089761.
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Effects of wine on blood pressure, glucose parameters, and lipid profile in type 2 diabetes mellitus: A meta-analysis of randomized interventional trials (PRISMA Compliant).
Ye, J, Chen, X, Bao, L
Medicine. 2019;(23):e15771
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Abstract
BACKGROUND Previous studies identified conflicting results about the effects of wine intake on glucose parameters and the risk of cardiovascular diseases in type 2 diabetes mellitus (T2DM). The present study further investigated the association between wine digestion and these outcomes in T2DM patients. MATERIAL AND METHODS A search of PubMed, Embase, and Scopus databases (up to November 2018) was performed for randomized interventional trials which evaluated the effect of wine on blood pressure (BP), glucose parameters and lipid profiles in T2DM people. We used a variety of tests: fixed and random effects models, Q Cochrane test and I index, Egger and Begg tests, forest plots, and sensitivity analysis in our study. RESULTS A total of 9 randomized interventional studies were included in this meta-analysis. Overall, significant association between wine intake with diastolic BP (weighted mean difference [WMD] = 0.10; 95% confidence interval [95% CI]: -0.01 to 0.20, P = .03 I = 13%) and total cholesterol (TC) (WMD = 0.16, 95% CI: 0.02-0.31, P = .03, I = 6%), whereas no noticeable differences in glucose parameters, systolic BP, low-density lipoprotein cholesterol (LDLC), triglyceride (TG) and high-density lipoprotein cholesterol (HDLC) were identified between wine and controls groups (fasting glucose [FG],WMD = -0.00, 95% CI: -0.58 to 0.58; fasting insulin [FI], -0.22, -2.09 to 1.65; HbAc1%, -0.16, -0.40 to 0.07; systolic blood pressure, 0.12, -0.05 to 0.28; LDLC, -0.02, -0.25 to 0.21; TG, -0.34, -1.31 to 0.64; HDLC, 0.22, -0.08 to 0.53]. CONCLUSION This meta-analysis revealed that moderate wine consumption among T2DM patients could reduce the level of diastolic blood pressure and TC, but not glucose parameters and other cardiovascular risk factors.