Effect of combination treatment with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on incidence of cardiovascular and serious renal events: population based cohort study

Apr 25, 2024BMJ (Clinical research ed.)

Combined treatment with GLP-1 receptor agonists and SGLT-2 inhibitors linked to heart and kidney problems in a large population study

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Abstract

The combination of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors is associated with a 30% lower risk of major adverse cardiovascular events.

The combination therapy showed a 57% lower risk of serious renal events compared to glucagon-like peptide-1 receptor agonists alone.
When compared to sodium-glucose cotransporter-2 inhibitors, the combination also indicated a 29% lower risk of major adverse cardiovascular events.
Serious renal events showed a wide confidence interval when comparing the combination with sodium-glucose cotransporter-2 inhibitors, indicating less certainty in that finding.
Secondary outcomes regarding individual components of major adverse cardiovascular events also suggested similar trends, although with wider confidence intervals.

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OBJECTIVE: To determine whether the combined use of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors is associated with a decreased risk of major adverse cardiovascular events and serious renal events compared with either drug class alone among patients with type 2 diabetes, and to assess the effect of the combination on the individual components of major adverse cardiovascular events, heart failure, and all cause mortality.

DESIGN: Population based cohort study using a prevalent new-user design, emulating a trial.

SETTING: UK Clinical Practice Research Datalink linked to Hospital Episode Statistics Admitted Patient Care and Office for National Statistics databases.

PARTICIPANTS: Two prevalent new-user cohorts were assembled between January 2013 and December 2020, with follow-up until the end of March 2021. The first cohort included 6696 patients who started GLP-1 receptor agonists and added on SGLT-2 inhibitors, and the second included 8942 patients who started SGLT-2 inhibitors and added on GLP-1 receptor agonists. Combination users were matched, in a 1:1 ratio, to patients prescribed the same background drug, duration of background drug, and time conditional propensity score.

MAIN OUTCOME MEASURES: Cox proportional hazards models were fitted to estimate the hazard ratios and 95% confidence intervals of major adverse cardiovascular events and serious renal events, separately, comparing the GLP-1 receptor agonist-SGLT-2 inhibitor combination with the background drug, either GLP-1 receptor agonists or SGLT-2 inhibitors, depending on the cohort. Secondary outcomes included associations with the individual components of major adverse cardiovascular events (myocardial infarction, ischaemic stroke, cardiovascular mortality), heart failure, and all cause mortality.

RESULTS: Compared with GLP-1 receptor agonists, the SGLT-2 inhibitor-GLP-1 receptor agonist combination was associated with a 30% lower risk of major adverse cardiovascular events (7.010.3 events per 1000 person years; hazard ratio 0.70, 95% confidence interval 0.49 to 0.99) and a 57% lower risk of serious renal events (2.04.6 events per 1000 person years; hazard ratio 0.43, 0.23 to 0.80). Compared with SGLT-2 inhibitors, the GLP-1 receptor agonist-SGLT-2 inhibitor combination was associated with a 29% lower risk of major adverse cardiovascular events (7.610.7 events per 1000 person years; hazard ratio 0.71, 0.52 to 0.98), whereas serious renal events generated a wide confidence interval (1.42.0 events per 1000 person years; hazard ratio 0.67, 0.32 to 1.41). Secondary outcomes generated similar results but with wider confidence intervals. v v v v

CONCLUSIONS: In this cohort study, the GLP-1 receptor agonist-SGLT-2 inhibitor combination was associated with a lower risk of major adverse cardiovascular events and serious renal events compared with either drug class alone.

Key numbers

30%

Decrease in Major Adverse Cardiovascular Events

Compared to GLP-1 receptor agonists alone

57%

Decrease in Serious Renal Events

Compared to GLP-1 receptor agonists

29%

Decrease in Major Adverse Cardiovascular Events

Compared to SGLT-2 inhibitors

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Effect of combination treatment with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on incidence of cardiovascular and serious renal events: population based cohort study

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