Do SGLT2 inhibitors with or without metformin improve heart and kidney health?

This review looked at how SGTL2 inhibitors with or without metformin (Glucophage) affect heart and kidney health for patients with type 2 diabetes (T2D). It found that these medications improve cardiovascular and kidney outcomes, whether or not patients are also taking metformin.

SGLT2 inhibitors are a group of T2D medications, including canagliflozin (Invokana) and empagliflozin (Jardiance). These medications alter the way the kidneys process glucose (sugar). The kidneys separate plasma, which includes wastes and excess fluids, from the rest of the blood. Then, glucose and other nutrients in the plasma are absorbed back into the blood. SGLT2 inhibitors block glucose from being reabsorbed, so it passes out of the body in the urine.

Over time, high blood glucose from T2D can damage the kidneys. SGLT2 inhibitors reduce kidney damage. These medications also reduce heart attack and stroke for patients with T2D.

SGLT2 inhibitors are not often the first medication prescribed for T2D. The first treatment is typically metformin, which reduces how much glucose the liver produces and alters how the body responds to glucose. It is not clear whether taking metformin at the same time affects the heart and kidney benefits of SLGT2 inhibitors.

This review included six studies of 51,743 patients with T2D and/or heart failure. Depending on which study, between 21% and 82% of patients were taking metformin. Half of the patients received an SLGT2 inhibitor, and half received a placebo (inactive pill) for comparison. The patients were followed for between 2.4 and 4.2 years.

SGLT2 inhibitors reduced the risk of worsening kidney function by 42% for patients who were also taking metformin. For patients who were not taking metformin, SGLT2 inhibitors reduced this risk by 37%.

Patients had a lower risk of heart attack, stroke, or other major cardiovascular events when taking SGLT2 inhibitors. The risk was 7% lower for those taking metformin, and 18% lower for those not taking metformin.

This review found that SGLT2 inhibitors improve heart and kidney health for patients with T2D, whether or not they are already taking metformin. The authors suggest that SGLT2 inhibitors may be appropriate as a first-line treatment for patients with both T2D and heart disease.

Most of the patients studied had T2D for an extended period. It is not clear whether these results apply to patients recently diagnosed with T2D.