Tilläggsbehandling med SGLT2-hämmare och GLP-1-receptoragonister hos patienter med typ 2-diabetes och risk för hjärt- och kärlsjukdom eller njursjukdom

Här sammanfattar och kommenterar SBU en systematisk översikt som publicerades i BMJ i början av 2021. 

https://www.sbu.se/sv/publikationer/sbu-kommentar/sbuk202207/

Översiktens fråga

Vilka effekter har tillägg av SGLT2-hämmare och GLP-1-receptoragonister till befintlig diabetesbehandling hos patienter med olika risknivåer för hjärt- och kärlsjukdom eller njursjukdom?

SBU:s svar

Översiktsförfattarna sammanfattar att behandling med antingen SGLT2-hämmare eller GLP-1-receptoragonister, som tillägg till befintlig diabetesbehandling, minskar dödlighet, icke fatal hjärtinfarkt samt njursvikt (hög tillförlitlighet). Den absoluta positiva effekten av läkemedlen varierade väsentligt beroende på risknivå vid behandlingsstart. SBU konstaterar att denna tolkning av det vetenskapliga underlaget är relevant.

Vem skriver vi för

I första hand riktar sig denna kommentar till beslutsfattare och receptförskrivande läkare.

Kommenterad systematisk översikt och nätverksmetaanalys:

Palmer SC, Tendal B, Mustafa RA, Vandvik PO, Li S, Hao Q, et al. 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. BMJ. 2021;372:m4573. Available from:

https://doi.org/10.1136/bmj.m4573

Research

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

BMJ 2021; 372 doi: https://doi.org/10.1136/bmj.m4573 (Published 13 January 2021)Cite this as: BMJ 2021;372: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.

Utdrag ur artikeln

Discussion

Principal findings

This network meta-analysis provides high certainty evidence that SGLT-2 inhibitors and GLP-1 receptor agonists, when added to other diabetes treatment, reduce mortality, non-fatal myocardial infarction, kidney failure, and serious hyperglycaemia.

In the absence of head-to-head trials, we also found high certainty evidence for notable differences between SGLT-2 inhibitors and GLP-1 receptor agonists; SGLT-2 inhibitors reduced admission to hospital for heart failure more than GLP-1 receptor agonists, whereas GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect).

Differential effects of SGLT-2 inhibitors and GLP-1 receptor agonists on other patient important outcomes included lower body weight and increased quality of life, albeit with small absolute differences. Harms also differed.

SGLT-2 inhibitors caused genital infection, and GLP-1 receptor agonists might increase severe gastrointestinal events. Importantly, the absolute benefits for cardiovascular and renal outcomes varied substantially for patients, depending on their absolute cardiovascular risk (very low to very high; https://magicevidence.org/match-it/200820dist/#!/) Taken together, the results have clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by our systematic review.

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https://www.bmj.com/content/372/bmj.m4573

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