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

Jan 14, 2021BMJ (Clinical research ed.)

Comparing SGLT-2 inhibitors and GLP-1 receptor agonists for type 2 diabetes: review and analysis of clinical trials

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Abstract

A network meta-analysis of 764 trials involving 421,346 patients found that and reduced all-cause mortality and cardiovascular events in patients with type 2 diabetes.

Both SGLT-2 inhibitors and GLP-1 receptor agonists are associated with lower rates of all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure.
SGLT-2 inhibitors are linked to a greater reduction in hospital admissions for heart failure compared to GLP-1 receptor agonists.
GLP-1 receptor agonists are associated with a greater reduction in non-fatal strokes than SGLT-2 inhibitors, which showed no effect on this outcome.
SGLT-2 inhibitors are linked to a higher incidence of genital infections, while GLP-1 receptor agonists may cause severe gastrointestinal events, though this finding has lower certainty.
Evidence suggests that both drug classes may lower body weight, but certainty is low.
No significant effects were found for limb amputation, blindness, eye disease, neuropathic pain, or health-related quality of life.

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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 or 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.

Key numbers

40 fewer per 1000 patients

Reduction in All-Cause Mortality

Absolute benefit over five years for very high-risk patients

58 fewer per 1000 patients

Reduction in Hospital Admissions for Heart Failure

Absolute benefit over five years for very high-risk patients

25 fewer per 1000 patients

Reduction in Non-Fatal Stroke

Absolute benefit over five years for very high-risk patients

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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

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