Can novel non-insulin therapies for patients with type 2 diabetes prevent heart disease?

This study examined how frequent heart disease is among patients taking different non-insulin medications for type 2 diabetes (T2D). The results showed that certain medications significantly reduced the risk of patients developing heart disease and other complications of T2D.

Heart disease is a serious complication in patients with T2D. Heart disease can lead to heart attacks and is linked to a higher risk of strokes. Some studies have shown that recent non-insulin therapies for T2D may also reduce the risk of developing heart disease. However, it is difficult to know how effective each therapy is as they are usually used in combination with other drugs. 

These recent therapies include sodium-glucose transporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitor (DPP-4i), and glucagon-like peptide-1 agonists (GLP-1a). An understanding of the effects of these therapies on heart disease may be useful for patients at a higher risk of heart disease.

Data from 118,341 patients with T2D were analyzed. 57,293 patients received sulfonylurea medications. 41,045 patients received DPP-4i. 12,796 patients received GLP-1a. 7,207 patients received SGLT-2i. All patients also received metformin (Glucophage). Patients were followed for an average of 10 months.

Overall, 1046 patients had a heart or blood vessel complication. Patients receiving DPP-4i had a 21% lower risk of developing complications than those taking a sulfonylurea. Compared to sulfonylurea, this risk was 35% lower in GLP-1a users and 39% lower in SGLT-2i users. 

The total number of patients who had heart failure, a stroke, or heart surgery was 2256 patients.  Patients receiving DPP-4i had a 19% lower risk of developing heart failure, stroke, or heart surgery than those taking a sulfonylurea. Compared to sulfonylurea, this risk was 28% lower in those taking GLP-1a and 38% lower in those taking SGLT-2i.

Overall, 4899 other side effects were reported. These included hypoglycemia (dangerously low blood glucose levels), pancreas inflammation, urinary tract infections, genital yeast infections, or lower limb amputation. The risk of side effects was lower in GLP-1a (by 16%), DPP-4i (by 26%), and SGLT-2i (by 32%) users compared to patients receiving sulfonylurea. 

The authors concluded that SGLT-2i, GLP-1a, and DPP-4i reduced the risk of developing heart disease, stroke, and other side effects compared to sulfonylurea.

The study was limited by its short follow-up. There were not equal numbers of patients receiving each therapy. These results do not account for which drugs control blood glucose best or if patients had an active lifestyle. Patients receiving SGLT-2i and GLP-1a therapies were receiving a mix of different brands.