Can exenatide and dapagliflozin reduce weight, blood pressure, and triglycerides?

This study examined the effects of dapagliflozin (Farxiga) and exenatide (Byetta) in different groups of people with type 2 diabetes (T2D). It was determined that a combination of the drugs reduces weight, blood pressure, and triglycerides (type of fat found in the blood) more than either alone. The greatest reductions were seen in people who started with high weight, high blood pressure, and normal triglyceride levels.

Metformin (Glucophage) is the first drug given to most people with T2D. Eventually, many people with T2D will need more than one therapy.

Exenatide is a glucagon-like peptide 1 receptor agonist (GLP1RA). Glucagon-like peptide 1 (GLP1) is made in the intestines and released after a meal. GLP-1 stimulates the release of insulin (the hormone that lowers blood glucose) and inhibits the release of glucagon (hormone that raises blood glucose). These hormonal changes control blood glucose levels. GLP1RAs are drugs that mimic the effects of GLP1.

Dapagliflozin is an SGLT2 inhibitor. SGLT2 is a protein in the kidneys that is important in controlling blood glucose levels. It allows glucose to re-enter the blood from the kidneys. SGLT2 inhibitors are a type of treatment that prevents this.

People with T2D are at increased risk of developing cardiovascular diseases, which can cause heart attacks and strokes. People who are also overweight or obese, who have high blood pressure, or high triglycerides (type of fat in the blood) are at an even higher risk. Therapies that reduce weight, blood pressure, and triglycerides may also reduce the risk of cardiovascular disease. Exenatide and dapagliflozin have both been shown to do this, in addition to their effects on glucose levels. However, it is not clear how different groups of people with T2D are affected.

Just under 600 adults with T2D, who were already being treated with metformin, were recruited for this study. They were divided into 3 groups. Group 1 received exenatide and dapagliflozin in addition to their normal metformin. Group 2 received only exenatide and metformin. Group 3 received only dapagliflozin and metformin. They were followed up after 28 weeks of treatment.

People in group 1 lost more weight than people in groups 2 and 3. In each group, more weight was lost by people who were obese at the start of the study than people who were overweight at the start of the study.

Blood pressure was reduced more in group 1 than in groups 2 and 3. People in groups 1 and 2 who had high blood pressure at the start of the study had greater reductions in blood pressure than people who had normal blood pressure at the start. People with normal or high blood pressure in group 3 had similar reductions in blood pressure.

Triglycerides were reduced the most in group 1, followed by group 2. The smallest reductions were seen in group 3. In group 3, dapagliflozin did not reduce triglycerides in people who had high triglycerides at the start of the study. In all groups, people with normal triglycerides had greater reductions than people with high triglycerides.

The study concluded that the combination of dapagliflozin and exenatide reduced weight, blood pressure, and triglycerides, more than either drug alone. The greatest reductions were seen in people with high weight, high blood pressure, and normal triglycerides. 

This study was funded by AstraZeneca, the manufacturers of dapagliflozin and exenatide. Only a small number of participants had normal weight, normal blood pressure, and normal triglyceride levels. This may have limited comparisons.

Discuss the effects of dapagliflozin and exenatide on weight, blood pressure, and triglycerides with your physician.