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


Suetonia C Palmer 1, Britta Tendal 2, Reem A Mustafa 3 4, Per Olav Vandvik 5, Sheyu Li 6 7, Qiukui Hao 8, David Tunnicliffe 9, Marinella Ruospo 10, Patrizia Natale 9 10, Valeria Saglimbene 10, Antonio Nicolucci 11, David W Johnson 12, Marcello Tonelli 13, Maria Chiara Rossi 11, Sunil V Badve 14, Yeoungjee Cho 12, Annie-Claire Nadeau-Fredette 15, Michael Burke 16, Labib I Faruque 17, Anita Lloyd 17, Nasreen Ahmad 17, Yuanchen Liu 17, Sophanny Tiv 17, Tanya Millard 2, Lucia Gagliardi 18 19, Nithin Kolanu 20, Rahul D Barmanray 21, Rita McMorrow 22, Ana Karina Raygoza Cortez 23, Heath White 2, Xiangyang Chen 6, Xu Zhou 24, Jiali Liu 25, Andrea Flores Rodríguez 23, Alejandro Díaz González-Colmenero 23, Yang Wang 26, Ling Li 25, Surya Sutanto 27, Ricardo Cesar Solis 23, Fernando Díaz González-Colmenero 23, René Rodriguez-Gutierrez 23, Michael Walsh 28 29, Gordon Guyatt 4, Giovanni F M Strippoli 30 10

Main idea: In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with notable 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.


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: Randomized controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose-lowering treatment. Studies were screened independently by two reviewers for eligibility.

Random effects network meta-analysis was carried out. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors) and very high risk (cardiovascular disease and kidney disease) 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. Little or no evidence was found for the effect 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. See interactive decision support tool (!%) for all outcomes.


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