Practice Update: Diabetes

ADA 2017 9

SGLT2 Inhibitors are Associated with Reduced Cardiovascular Disease in Patients with Type 2 Diabetes The new medication class, sodium-glucose transporter-2 (SGLT2) inhibitors, has been associated with lower rates of death and hospitalization for heart failure in patients with type 2 diabetes, both with and without existing cardiovascular disease, and regardless of the specific SGLT2 inhibitor used. T his outcome of the population-based Hospitalization for Heart Failure and Death inNewUsers of SGLT2 Inhibitors

matching, baseline characteristics were balanced between groups, and 306,156 patients, >150,000 person years (100,947 person years for SGLT2 inhibitors; 89,208 person years for other glucose-lowering drugs) and 950 new heart failure events were analyzed. Hazard ratios for heart fail- ure, death, and the composite of death or heart failure were estimated by country and pooled as a weighted average. An association between SGLT2 inhibitors and lower rates of death due to heart fail- ure and hospitalization for heart failure was seen in all five participating countries. Fur- thermore, the benefits of SGLT2 inhibitor treatments were consistent regardless of the type of SGLT2 inhibitor used, which var- ied from country to country. SGLT2 inhibitors vs other glucose-lowering drugs were associated with 31% lower rates of heart failure in patients with existing and 45% without existing cardiovascular dis- ease (hazard ratio 0.69, 95% confidence interval 0.59–0.80; hazard ratio 0.55, 95% confidence interval 0.34–0.88). Similar results were seen for death and death due to heart failure regardless of whether patients had a history of cardiovascular disease. All patients treatedwith SGLT2 inhib- itors were less likely to suffer heart failure or subsequent death vs patients receiving other glucose-lowering drugs. Dr Cavender concluded, “Results of this study offer further evidence regarding the to week 24 and adverse events. At 24-weeks, alirocumab reduced LDL-C significantly, by 49% vs placebo and improved other lipid parameters as well. Further, 80% of patients reached rec- ommended target LDL-C levels with alirocumab 75 mg. Dr Leiter concluded that co-administration of alirocumab and insulin was safe and the incidence of adverse events was generally similar between alirocumab and placebo. Additionally, alirocumab was well tolerated and did not affect glucose control. Results were comparable to those seen in previ- ous ODYSSEY trials. This study also evaluated the effect of ali- rocumab on some newer lipid parameters that will enable a better understanding of

potential of SGLT2 inhibitors to improve outcomes in patients with diabetes. While our results were striking in their similar- ity to a prior randomized study evaluating the benefit of SGLT2 inhibitors in patients with diabetes and known cardiovascular disease, the results went one step further to show that SGLT2 inhibition may benefit patients with diabetes regardless of whether they harbor known cardiovascular disease. It is also important to note the significant difference in the particular SGLT2-inhib- itor used in each country. This difference suggested that benefits seen with SGLT2 inhibitors were likely a class effect. Research has shown that patients with diabetes are at 30% higher risk of heart failure vs patients without diabetes. These findings suggested that use of SGLT2 inhibitors may provide the opportunity to reduce the incidence of heart failure among patients with diabetes.” Ongoing randomized clinical trials with SGLT2 inhibitors are likely to provide con- siderable additional information regarding their clinical effectiveness. As a follow-up to this study, the effectiveness of SGLT2 inhib- itors on other important clinical events are being further evaluated. Such evaluation will broaden the study’s focus on associations between other drugs for patients with diabe- tes and a history of cardiovascular events. www.practiceupdate.com/c/54675 the effect of alirocumab on atherogenic diabetic dyslipidemia. Atherogenic diabetic dyslipidemia is caused by insulin resist- ance primarily, and is characterized by high serum triglycerides, elevated LDL levels, low HDL levels, and postprandial lipemia. Dr Leiter concluded, “Results of the ODYS- SEY DM-Insulin study provided valuable information on the efficacy and safety of alirocumab in this high cardiovascular risk group and will help guide clinical deci- sion-making beyond statin therapy.” Results on the efficacy and safety of aliro- cumab in patients with type 1 diabetes will be reported at a later date. www.practiceupdate.com/c/54540 PracticeUpdate Editorial team.

in Patients With and Without Cardiovascular Disease (CVD-REAL) trial was reported at This outcome of the international phase 3, rand- omized, double-blind, placebo-controlled ODYSSEY-DM Insulin Trial was reported at the American Diabetes Association’s 77th Scientific Sessions, from June 9–13. Matthew A. Cavender, MD, MPH, of the University of North Carolina School of Med- icine in Chapel Hill, explained that SGLT2 is a protein responsible for glucose regula- tion. SGLT2 inhibitors reduce renal glucose reabsorption by causing excess blood glu- cose to be expelled through urine. The CVD-REAL study analyzed outcomes of 306,156 patients with type 2 diabetes from the US, UK, Norway, Sweden, and Denmark who were treated with SGLT2 inhibitors. Using data from clinical practice, Dr Cav- ender and colleagues compared rates of heart failure and death in patients with and without prior cardiovascular disease vs heart failure rates in new users of SGLT2 inhibitors and other glucose-lowering drugs. Data on heart failure and subse- quent death rates were collected using medical records, medical claims, electronic health records, and national registers. Propensity scores were used to match patients treated with SGLT2 inhibitors and other glucose-lowering drugs. After Dr Leiter presented results of patients with type 2 diabetes (n = 441, LDL-C ≥70 mg/dL (1.81 mmoL/L). They were taking either tak- ing the maximum tolerated statin dose or were unable to tolerate any statin. Addi- tionally, they harbored atherosclerotic cardiovascular disease or at least one other cardiovascular risk factor. Patients were randomized to either an injection of 75 mg of alirocumab (n = 294) or placebo (n = 147) injection once every 2 weeks. Patients in the alirocumab group whose LDL-C was ≥70 mg/dL at 8 weeks received a blinded dose increase to 150 mg at week 12. Primary endpoints were the difference between treatment arms in percentage change of calculated LDL-C from baseline

PracticeUpdate Editorial team.

VOL. 1 • NO. 2 • 2017