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

AbstractObjectiveTo 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.DesignNetwork meta-analysis.Data sourcesMedline, Embase, and Cochrane CENTRAL up to 11 Augus...

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Veröffentlicht in:BMJ (Online) Jg. 372; S. m4573
Hauptverfasser: Palmer, Suetonia C, Tendal, Britta, Mustafa, Reem A, Vandvik, Per Olav, Li, Sheyu, Hao, Qiukui, Tunnicliffe, David, Ruospo, Marinella, Natale, Patrizia, Saglimbene, Valeria, Nicolucci, Antonio, Johnson, David W, Tonelli, Marcello, Rossi, Maria Chiara, Badve, Sunil V, Cho, Yeoungjee, Nadeau-Fredette, Annie-Claire, Burke, Michael, Faruque, Labib I, Lloyd, Anita, Ahmad, Nasreen, Liu, Yuanchen, Tiv, Sophanny, Millard, Tanya, Gagliardi, Lucia, Kolanu, Nithin, Barmanray, Rahul D, McMorrow, Rita, Raygoza Cortez, Ana Karina, White, Heath, Chen, Xiangyang, Zhou, Xu, Liu, Jiali, Rodríguez, Andrea Flores, González-Colmenero, Alejandro Díaz, Wang, Yang, Li, Ling, Sutanto, Surya, Solis, Ricardo Cesar, Díaz González-Colmenero, Fernando, Rodriguez-Gutierrez, René, Walsh, Michael, Guyatt, Gordon, Strippoli, Giovanni F M
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England British Medical Journal Publishing Group 13.01.2021
BMJ Publishing Group LTD
BMJ Publishing Group Ltd
Schlagworte:
Agonists
Amputation
Bias
Blindness
Body weight
Cardiovascular disease
Cardiovascular diseases
Cardiovascular Diseases - epidemiology
Cerebral infarction
Clinical trials
Congestive heart failure
Diabetes
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - drug therapy
Diabetic neuropathy
Estimates
Eye diseases
GLP-1 receptor agonists
Glucagon
Glucagon-like peptide 1
Glucagon-Like Peptide-1 Receptor Agonists
Glucose
Hemoglobin
Humans
Hypoglycemic Agents - adverse effects
Hypoglycemic Agents - therapeutic use
Kidney diseases
Meta-analysis
Mortality
Myocardial infarction
Patients
Peptides
Placebos
Quality of life
Randomized Controlled Trials as Topic
Renal failure
Renal Insufficiency - epidemiology
Risk factors
Sodium-glucose cotransporter
Sodium-Glucose Transporter 2 Inhibitors - adverse effects
Sodium-Glucose Transporter 2 Inhibitors - therapeutic use
Standard deviation
Systematic review
ISSN:1756-1833, 0959-8138, 1756-1833
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Zusammenfassung:AbstractObjectiveTo 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.DesignNetwork meta-analysis.Data sourcesMedline, Embase, and Cochrane CENTRAL up to 11 August 2020.Eligibility criteria for selecting studiesRandomised 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 measuresFrequentist 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.Results764 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.ConclusionsIn 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 registrationPROSPERO CRD42019153180.
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ISSN:1756-1833
0959-8138
1756-1833
DOI:10.1136/bmj.m4573