Benefits of GLP1 RA and SGLT-2 Inhibitors in Type 2 Patients

GLP1 RA and SGLT-2 were compared to evaluate coronary health disease reduction in patients with type 2 diabetes.

Diabetes is one of the chronic health conditions associated with more complications as patients age. This condition can lead to cardiovascular events, renal problems, blindness, amputations, nerve damage if left untreated, or if it is not well managed. Cardiovascular events are at the top of the list as severe complications, and are the primary cause of death in patients with type 2 diabetes. Data indicates that cardiovascular events in patients with diabetes can be up to 3 times more fatal than in those without diabetes. About 30% of patients with type 2 diabetes already have established cardiovascular disease. Identifying ways to maintain a controlled condition for decreasing these events’ risk is crucial for the patients. Challenges come when clinicians need to decide on the best treatment for type 2 diabetes patients. From the long list of current medications to treat type 2 diabetes, the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) are two classes of drugs that have shown some benefit in terms of cardiovascular diseases. 

In a recent observational retrospective study, clinicians evaluated the changes over time in cardiovascular risk in patients diagnosed with type 2 diabetes using GLP1-RAs and SGLT-2 inhibitors. Data from 2000 participants from Rome, Italy, was analyzed from September 2019 to February 2020. They included 321 patients starting on GLP1-RAs or SGLT-2 inhibitors with a visit record after six months of starting the medication. The baseline time was determined to be the first day the patient took the drug. Some data collection occurred after 6, 12, and 24 months of starting the medications, including HbA1C, lipid profile, blood pressure, smoking habits, comorbidities, uric acid, creatinine, and eGFR. As the primary outcome, they evaluated the risk of any cardiovascular event. Secondary outcomes included stroke, fatal stroke, and deadly coronary artery disease. 

There are a few cardiovascular risk assessments but, in this study, they used the U.K. Prospective Diabetes Study Risk Engine (UKPDS-RE) score to evaluate the long-term (10-year) cardiovascular risk. Some variables taken into consideration by the UKPDS-RE score include age, disease duration, gender, presence or absence of atrial fibrillation, ethnicity, smoking status, HbA1C, systolic blood pressure, total cholesterol, and HLD cholesterol. Categories of CHD risk were defined with tertiles first (mild or <11%), second (moderate or 12%-20%), and third (severe or ≥21%). As part of statistical analysis, they used t-tests, the Kruskal-Wallis test, the Fisher test, and a 90% power. Based on baseline scores and the number of patients, they predicted a 3% reduction in primary endpoints after one year of taking the medication. 

From the 321 patients included in the study, 174 started on GLP-1 RAs while 138 started on SGLT-2 inhibitors. None of these patients had previous cardiovascular disease diagnosed at baseline. Of the 321 patients, a higher percentage of women took GLP-1 RA than SGLT-2 Inhibitors (49% vs. 33%; p<0.004). Patients taking GLP-1 RA had lower HbA1C than those taking SGLT-2 inhibitors (8.0% vs. 8.7%; p<0.001). Also, these patients had a higher BMI (35.29 vs. 32.34 kg/m2; p<0.001). Clinicians observed that GLP-1 RA was more frequently prescribed in subjects with a history of carotid artery stenosis (21% vs. 8%; p<0.001). 

The 10-year risk of any coronary health disease decreased significantly in both GLP-1 RA (p=0.037) and SGLT-2 inhibitors (p<0.001). This outcome was observed at 6-month follow-up, and evaluations at 12 and 24-month reported the same trend (p<0.001). The clinicians adjusted the data for changes in statin medications and antihypertensive medications. In the study, coronary health disease risk improved in the severe risk category (p<0.001) but not in the mild or moderate categories. They observed a significant reduction of fatal coronary health diseases in patients taking SGLT-2 inhibitors only (p<0.001), but the stroke risk was significantly decreased in both groups at 6-month evaluation. 

Overall, the risk of coronary health diseases decreased significantly in both groups at six and 12-month evaluation (p<0.001) but lost significance at 24-month evaluation (p<0.067). A significant reduction in HbA1C and lipid panel components (except with the increase in HDL) was observed while patients were on SGLT-2 inhibitors and GLP-1 RA. Clinicians observed a reduction in uric acid levels and blood pressure only in patients taking SGLT-2 inhibitors. It was also reported that a higher percentage of patients taking SGLT-2 discontinued the medication after one year of use (9.3% vs. 2.4%; p<0.0009) due to inefficacy or side effects. 

The fact that this study had a small sample and was conducted in Europe limits generalizability. More studies should be performed with the U.S. population. The data reported in this observational study is similar to other studies. They reported an overall class benefit in reducing coronary health disease in both SGLT-2 inhibitors and GLP-1 RA. 

Practice Pearls: 

• GLP-1 RA and SGLT-2 inhibitors are associated with decreased coronary health disease risk. 
• Patients with higher UKPDS-RE scores reflected a more pronounced reduction over time in coronary health disease events. 
• Both drug classes can be considered for patients with a higher risk of cardiovascular diseases, and drug selection should be personalized. 

D’Onofrio, L, et al. Decrease of Coronary Heart Disease Risk with GLP1-Receptor Agonists or SGLT-2 Inhibitor’s Therapy in Patients with Type 2 Diabetes in Primary Cardiovascular Prevention: A 24 Months Follow-up Study. Diabetes Research and Clinical Practice (2021) 173.  

Lee, M, et al. How Do SGLT2 (Sodium-Glucose Cotransporter 2) Inhibitors and GLP-1 (Glucagon-Like Peptide-1) Receptor Agonists Reduce Cardiovascular Outcomes?: Completed and Ongoing Mechanistic Trials. Arterioscler Thromb Vasc Biol (2020); 40(3):506-522.  

Bertoccini, L. et al. GLP-1 Receptor Agonist and SGLT2 Inhibitors for the Treatment of Type 2 Diabetes: New Insight and Opportunities for Cardiovascular Protection. Adv Expo Med Biol (2021) 1307:193-212.  

Laura Martínez López, PharmD. Candidate 2021, Lake Erie College of Osteopathic Medicine, College of Pharmacy