SGLT-2 vs. GLP-1: Cardiovascular Outcomes in Adults with Type 2 Diabetes

Cardiovascular events decline for patients using which antidiabetic medication, SGLT-2 or GLP-1?

Life threatening cardiovascular events can take place with uncontrolled type 2 diabetes, including death, heart failure, stroke, and myocardial infarction. Patients can also suffer from acute kidney disease. The purpose of this study is to compare the use of two antidiabetic medications, SGLT-2 inhibitor and GLP-1 receptor agonist, as it pertains to cardiovascular events.  Previous studies, Dapagliflozin Effect on Cardiovascular Events (DECLARE) and Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) documented cardiovascular benefits for both medications.  Another analysis performed on Italian outpatients with diabetes found benefits in glycemic control, HbA1c, blood pressure, and body weights were comparable. The authors stated that no clinical trials determine which drug is more effective in type 2 patients to protect them from cardiovascular events.  

This study was an observational, retrospective study. The purpose was to determine the cardiovascular outcomes of type 2 diabetes patients taking SGLT2i or GLP-1RA during 2014-2018.  The population was selected from the North-East Italy region using databases to identify the patients. The primary outcome was the three-point major adverse cardiovascular events (3P-MACE):  myocardial infarction, stroke, or death.  The secondary endpoints consisted of the 3P-MACE, hospitalization for heart failure (HF), arterial revascularizations, and other cardiovascular causes for hospitalization.   

The participants matched using a 1:1 propensity score matching. The logistic regression model estimated propensity scores. Univariate tests determine the propensity score matching effectiveness, using Chi-square for the binary variables, and Mann-Whitney’s U tests for the other variables. The authors analyzed the patient’s laboratory tests, fasting glucose, HbA1c, cholesterol, and triglycerides. Hazard ratios were analyzed using a Cox regression. The study included four thousand two-hundred and ninety-eight matched with SGLT2i; nine hundred and sixty-two were presented with laboratory data.  For the GLP-1RA, four-thousand two hundred and ninety-eight with only eight hundred with laboratory data. The SGLT2i patients newly started either dapagliflozin, empagliflozin, or canagliflozin.  The GLP-1RA patients were on either liraglutide, exenatide, dulaglutide, or lixisenatide.  

The patients’ average age was 63 years old, with a higher percentage of male versus female patients. These patients had diabetes for an average of 9.5 years. Many of the patients had hypertension, dyslipidemia but there was low occurrence of cardiovascular disease. 3P-MACE events occurred in 257 patients (114 events in the SGLT2i group and 143 events in the GLP-1RA group). Incidences are seen in 21.8 events/100 person-years in SGLT2i patients compared to 27.9 in GLP-1RA patients. The Cox proportional hazard ratio was reported as statistically significant with HR of 0.78 (95% CI 0.61 – 0.99; P-value 0.043). The secondary outcomes presented with similar results; all were showing less in the SGLT2i group: myocardial infarction; HR 0.72; 95% CI 0.53-0.98; P-value 0.035, heart failure; HR 0.59; 95% CI 0.35 – 0.99; P-value 0.048, and hospitalization for CVD HR 0.82 CI 0.82; 95% CI 0.69-0.99; P-value 0.037. These results are all significantly inclusive to SGLT2i. The study results were reported for as treated and intention to treat. From the 3P-MACE, all were in favor of SGlT2i except for stroke, as it was better controlled in GLP-1RA. Changes seen in blood pressure, triglycerides, and cholesterol were significantly favored in SGLT2i. Data collected for adverse effects reported two diabetic ketoacidosis cases in both groups; ten amputations in the SGLT2i group and only six in the GLP-1RA group. Acute kidney incidence occurred more in the GLP-1RA group.   

The authors concluded that patients with type 2 diabetes showed a lowered rate of cardiovascular events when starting SGLT2i therapy compared to GLP-1RA. For all the endpoints besides stroke, SGLT2i was significantly superior over GLP-1RA, as seen for myocardial infarction and hospitalization for heart failure. The limitations of the study were that it was not randomized with a control population and confounding indications. The authors stated this study “provides medium-level evidence that SGLT2i may be more effective than GLP-1RA in preventing cardiovascular events in Type 2 diabetes patients seen during routine care, few of who had pre-existing cardiovascular disease, and who had been previously treated with a complex regimen of glucose-lowering medications.”  Future studies need to be conducted using a randomized control trial to randomize the population.  

Practice Pearls 

• The antidiabetic medication class of SGLT2 inhibitors may lower type 2 diabetes patients’ cardiovascular events. 
• Controlling type 2 diabetes with antidiabetic medications reduces patient hypertension, blood glucose, and cholesterol. 
• SGLT2 inhibitors may reduce hospitalization of type 2 diabetes patients. 

Longato E, Di Camillo B, Sparacino G, et al. Cardiovascular outcomes of type 2 diabetic patients treated with SGLT-2 inhibitors versus GLP-1 receptor agonists in real-life BMJ Open Diabetes Research and Care 2020;8:e001451. doi: 10.1136/bmjdrc-2020-001451 

Tarshay Boyd, PharmD. Candidate, LECOM School of Pharmacy