SGLT2 Inhibitors Can Reduce Cardiometabolic Risk in People with Diabetes Using Metformin

Data from a matched comparator study using UK primary care electronic health record data offers clinicians with new insight into the apparent reductions in cardiorenal risk observed with adding SGLT2 inhibitors into treatment algorithms for people with type 2 diabetes already using metformin.

Results of the study, which compared metformin users prescribed SGLT2 inhibitors to those not using an SGLT2 inhibitor, indicate those starting an SGLT2 inhibitor had a 44% reduction in risk of all-cause mortality, a 50% reduction in risk of severe renal disease, and a 25% reduction in risk of the study’s composite cardiovascular outcome compared to those who did not start use an SGLT2 inhibitor during the study period, with these apparent risk reductions irrespective of baseline chronic kidney disease.

“These results confirm that the benefits of SGLT2 inhibitors in patients with type 2 diabetes observed in clinical trials are applicable to populations at low CV risk in real-world settings, thereby supporting an increasing role of SGLT2 inhibitors in diabetes care,” investigators wrote.

As trial after trial has come forth purporting the cardiorenal protective benefits of SGLT2 inhibitor use in various populations, the research interest has begun to shift to implementation science and whether these benefits translate to real-world populations. Citing an interest in exploring the effects of agents within the class outside of the clinical trial setting, the current study was designed by investigators as a matched comparators study to compare risk of multiple adverse outcomes among patients with diabetes using metformin based on whether or not they initiated therapy with an SGLT2 inhibitor.

Using primary care electronic health care records, investigators created 2 cohorts of patients with diabetes, with 12,978 SGLT2 inhibitors and 44,286 nonusers identified for inclusion in the study. Using these patients, investigators planned to Cox regression models to assess associations between use of SGLT2 inhibitors and multiple outcomes of interest. For the purpose of analysis, outcomes of interest included a composite cardiovascular outcome, severe renal disease, and all-cause mortality. Investigators defined the composite cardiovascular outcome as nonfatal myocardial infarction, nonfatal ischemic stroke requiring hospitalization, and cardiovascular death.

Investigators pointed out the mean age and sex distribution as well as prevalence of comorbidities and frailty were similar between the study cohorts. The mean follow-up was 2.3 years for the SGLT2 inhibitor cohort and 2.1 years for the nonuser cohort.

Upon analysis, results indicated new users of SGLT2 inhibitors had a 25% reduction in risk of the composite cardiovascular outcome (HR, 0.75 [95% CI, 0.61-0.93]), a 45% reduction in risk of severe renal disease (HR, 0.55 [95% CI, 0.46-0.67]), and a 44% reduction in risk of all-cause mortality (HR, 0.56 [95% CI, 0.49-0.63]). Investigators pointed out these risk reductions were similar across groups defined by presence of baseline chronic kidney disease. Additionally, investigators pointed out the reduction in risk was observed for nonfatal ischemic stroke (HR, 0.51 [95% CI, 0.36-0.74]) but not for nonfatal myocardial infarction (HR, 0.98 [95% CI, 0.74-1.28]).

“Our results indicate that among individuals with type 2 diabetes on metformin, use of SGLT2 is associated with significant CV, renal and survival benefits under normal conditions of use, confirming findings from RCTs on this topic,” investigators concluded. “However, it is important to be aware of the level of unmet need that still exists in this patient population, as shown in the high incidence of CV and renal outcomes in this present study, especially among those with concurrent CKD.”

This study, “Cardiovascular and renal outcomes among patients with type 2 diabetes using SGLT2 inhibitors added to metformin: a population-based cohort study from the UK,” was published in BMJ Open Diabetes Research & Care.