Investigating a combination of ertugliflozin and sitagliptin in people with type 2 diabetes

This study investigated the effectiveness and safety of ertugliflozin (Steglatro) plus sitagliptin (Januvia), compared to either drug used alone, in people with type 2 diabetes (T2D). It was determined that the combination was better at controlling blood glucose levels, without increasing the risk of side effects.

When people with T2D begin drug treatment, they usually start with metformin (Glucophage). If metformin does not control blood glucose levels, a single second agent is usually added. However, this may not control blood glucose in all people. Thus, it may be useful to add two drugs.

Ertuglilflozin 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.

Sitagliptin is a dipeptidyl peptidase-4 (DPP4) inhibitor. DPP4 inhibitors prevent the breakdown of glucagon-like peptide 1 (GLP1). GLP1 is made in the intestines and released after a meal. GLP1 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.

Ertugliflozin and sitagliptin work in different ways to control blood glucose. For this reason, the combination may be better at controlling blood glucose than either alone. 

1233 adults with T2D, whose blood glucose was not controlled with metformin, were recruited for this study. They were randomly divided into different groups. Some received ertugliflozin alone (group 1). Another group received sitagliptin alone (group 2). Others received a combination of the two drugs (group 3). The participants were followed up after 6 months and 1 year.

After 6 months, HbA1c (measures average blood glucose over the last 3 months) was reduced more in group 3 than in the other groups. HbA1c decreased by 1.5% in group 3, compared to 1.0-1.1% in the other groups. Those with higher HbA1c levels at the start of the study had greater reductions in HbA1c.

After 6 months, 49.2% to 52.3% of those in group 3 had HbA1c levels less than 7.0% (demonstrates good control of blood glucose levels). Only 26.4%-32.8% of those in groups 1 or 2 had HbA1c levels less than 7% after 6 months.

Fasting blood glucose (blood glucose after a period without food or drink) was reduced more in those in group 3. Body weight and blood pressure were significantly decreased in group 3 compared to group 2. Body weight and blood pressure reductions were similar in groups 1 and 3.

Effects on blood glucose control, body weight, and blood pressure after 1 year were similar to the 6 month results.

Patients treated with ertugliflozin (alone or in combination) were more likely to experience genital infections than those treated with sitagliptin. The occurrence of symptomatic hypoglycemia (dangerously low blood glucose), urinary tract infections, and hypovolemia (low body fluid volume), was low and similar between groups.

The study concluded that a combination of ertugliflozin and sitagliptin is better at controlling blood glucose than either alone. It also concluded that the combination did not significantly increase the risk of side effects.

This study was funded by Merck & Co., in collaboration with Pfizer. These companies manufacture ertugliflozin and sitaglitpin.

Discuss the combination of ertugliflozin and sitagliptin (and similar drugs) with your physician.