Beneficial effects found with combined usage of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors

1. Compared with using only using a GLP-1 receptor agonist or an SGLT-2 inhibitor, combination therapy with both drug classes was associated with a reduced risk of major adverse cardiac events (MACEs) and serious renal events.

2. The risk of serious renal events occurring was lower among those treated with GLP-1 receptor agonist-SGLT-2 inhibitor combination therapy. 

Evidence Rating Level: 2 (Good) 

Individually, Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotranspotor-2 (SGLT-2) inhibitors have had useful effects at decreasing the risk of cardiorenal events and mortality occurring in patients with type II diabetes. However, the combined effects have not been thoroughly understood. To further study the combined effects of the drugs, a population-based cohort study was conducted using the UK Clinical Practice Research Datalink (DPRD) GOLD along with other databases. The combination drugs were compared with either drug class alone or with other antihyperglycemic drugs through the use of a prevalent new-user design, which is able to mirror a randomized controlled trial. Two cohorts were created. The first cohort compared individuals previously using a GLP-1 receptor agonist and then adding on an AGLT-2 inhibitor to individuals with continued use of a GLP-1 receptor agonist. The other cohort compared patients with previous use of an SGLT-2 inhibitor and added a GLP-1 receptor agonist to patients with continued use of an SGLT-2 inhibitor. For the primary outcomes, cardiorenal events were split into cardiovascular events (including myocardial infarction, ischemic stroke, and cardiovascular mortality) and renal events (including chronic renal disease, unspecified kidney failure, and diabetes renal complications). Compared with only using a GLP-1 receptor agonist, combining a GLP-1 receptor agonist with an SGLT-2 inhibitor as a treatment was associated with a 30% lower risk of major adverse cardiovascular events (MACE) (7.0 v 10.3 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 (2.0 v 4.6 events per 1000 person-years; hazard ratio 0.43, 0.23 to 0.80). After one year, the number needed to treat to prevent one MACE was 378 while after three years it was 131. Compared with solely using an SGLT-2 inhibitor, the combined use of GLP-1 receptor agonist-SGLT-2 inhibitor was associated with a 29% decreased risk of MACE (7.6 v 10.7 per 1000 person-years; hazard ratio 0.71, 0.52 to 0.98) and a wide confidence interval for serious renal events (1.4 v 2.0 events per 1000 person years; hazard ratio 0.67, 0.32 to 1.41). The number needed to treat one adverse cardiovascular event decreased from 221 after one year to 86 after three years. In all, using a GLP-1 receptor agonist combined with an SGLT-2 inhibitor was associated with decreased risk of major cardiovascular and renal events compared with using each drug alone in type II diabetic patients. 

Click to read the study in BMJ

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