Combination SGLT2, GLP-1 therapy lowers risk for adverse CV outcomes in type 2 diabetes
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Combined use of an SGLT2 inhibitor and GLP-1 receptor agonist is associated with reduced odds for major adverse cardiac and cerebrovascular events and heart failure in adults with type 2 diabetes, according to study findings.
In an analysis of data from more than 300,000 adults with type 2 diabetes registered in three medical databases in England and Wales, the use of an SGLT2 inhibitor alone or combined SGLT2 inhibitor and GLP-1 receptor agonist therapy was associated with lower odds for major adverse cardiac and cerebrovascular events (MACCE) and heart failure (HF) compared with other treatment regimens, and those who were on a GLP-1 receptor agonist alone had lower odds for HF.
“American Diabetes Association and European Association for the Study of Diabetes guidelines were recently updated to reflect current evidence, with a new recommendation to use SGLT2 inhibitors and GLP-1 receptor agonists in high-risk patients,” Alison K. Wright, BSc, MSc, PhD, research associate in the division of diabetes, endocrinology and gastroenterology at the University of Manchester School of Medical Sciences, and colleagues wrote in a study published in Diabetes Care. “The guidelines highlight that no studies have assessed cardiovascular disease or renal benefits in low-risk patients with type 2 diabetes. We show that in primary prevention, use of these agents is associated with lower odds of MACCE for SGLT2 inhibitors and HF for SGLT2 inhibitors and GLP-1 receptor agonists, and that combination therapy could be especially useful to prevent MACCE.”
Researchers conducted a nested case-control study of data from three medical record databases: the Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases in England, and the Secure Anonymised Information Linkage (SAIL) Databank in Wales. Adults with type 2 diabetes prescribed a noninsulin diabetes medication from January 1998 to July 2018 who started at least one new class of medication between when SGLT2 inhibitors became available in the U.K. in November 2012 until the end of the study in July 2018 were included (n = 440,089). MACCE and HF were identified from primary care, hospital and mortality records. Diabetes medications were classified as combined SGLT2 and GLP-1 regimens, GLP-1 receptor agonists alone, SGLT2 inhibitors alone, other combination regimens excluding GLP-1 receptor agonists and SGLT2 inhibitors, other monotherapies or no medication.
SGLT2s, combination therapy lowers CVD risk
After excluding those with prior CVD, the study cohort had an unadjusted MACCE incidence rate of 18.1 per 1,000 person-years. Excluding those with a history of HF, the unadjusted incidence rate for HF was 13.9 per 1,000 person-years.
Of 18,490 adults who had a MACCE, 3.2% used an SGLT2 inhibitor, 2.5% used a GLP-1 receptor agonist and 0.3% used a combination of SGLT2 inhibitors and GLP-1 receptor agonists. Treatment with an SGLT2 inhibitor (adjusted OR = 0.82; 95% CI, 0.73-0.92) or a combined SGLT2 inhibitor and GLP-1 receptor agonist regimen (aOR = 0.7; 95% CI, 0.5-0.98) was associated with a lower likelihood for MACCE compared with other treatment regimens.
GLP-1, SGLT2 use lower HF risk
Of 17,428 adults who had HF, 2.8% used a GLP-1 receptor agonist, 1.7% used an SGLT2 inhibitor and 0.2% used both. Combination SGLT2 inhibitor and GLP-1 receptor agonist therapy (aOR = 0.43; 95% CI, 0.28-0.64), use of an SGLT2 inhibitor alone (aOR = 0.49; 95% CI, 0.42-0.58) and use of a GLP-1 receptor agonist alone (aOR = 0.82; 95% CI, 0.71-0.95) were associated with lower odds for HF compared with other diabetes medications.
“Ideally, confirmation of these results is needed before they can be incorporated into clinical decision-making frameworks,” the researchers wrote. “These data call for trials to evaluate the efficacy and cost-effectiveness of these interventions and their combination in the primary prevention setting. In view of the practical and economic issues associated with traditional trial designs, performing adequately powered pragmatic trials embedded within health care systems would be an attractive option.”
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