In another 12-week study, participants with an average starting HbA1c level of 7.8% were divided into four sitagliptin groups with different dose sizes and a placebo group. The group that received 100 mg once daily had the greatest average reduction in HbA1c level, 0.56%.
The three other studies tested daily doses of either 100 mg or 200 mg of sitagliptin over a period of 12–24 weeks. These studies showed average reductions in HbA1c level of 0.60% to 1.05%. Sitagliptin used alone to treat Type 2 diabetes generally lowered HbA1c levels 0.77% more than a placebo did.
Sitagliptin was also tested in combination with other drugs in four major trials. Three of the trials used sitagliptin combined with one other drug. These include studies that compared sitagliptin plus pioglitazone (Actos) with pioglitazone alone, and ones that compared sitagliptin plus metformin with both metformin alone and glipizide plus metformin. The studies ranged in length from 24 to 52 weeks. When sitagliptin was combined with metformin and with pioglitazone, the average HbA1c level of participants decreased by 0.65% and 0.70% more, respectively, than in those who took metformin alone and pioglitazone alone. When sitagliptin plus metformin was compared with glipizide plus metformin, there was no significant difference in reduction of HbA1c levels; both groups experienced an average drop of 0.67% (from an average starting HbA1c level of 7.5%).
Sitagliptin was also tested in combination with both glimepiride and metformin. (Like glipizide, glimepiride stimulates the pancreas to release more insulin.) In this study, participants were divided into four treatment groups, receiving either glimepiride only, sitagliptin and glimepiride, metformin and glimepiride, or sitagliptin, metformin, and glimepiride. Compared with glimepiride alone, the addition of sitagliptin reduced the average HbA1c level by 0.6% more, and compared with metformin plus glimepiride, the addition of sitagliptin caused a drop of 0.9% more.
Based on all of the studies mentioned, the recommended dose of sitagliptin is 100 mg taken once daily, either alone or in combination with metformin, a sulfonylurea drug such as glipizide or glimepiride, or a thiazolidinedione such as pioglitazone. It should be noted that these recommendations were created prior to the new warnings that thiazolidinediones may lead to an increased rate of heart problems, notably congestive heart failure. Sitagliptin is also available in a combination pill with metformin (Janumet) in two dose sizes.
Pros and cons
As the studies that were just described show, sitagliptin tends to lower HbA1c levels about as much as glipizide (and in some cases, not quite as much). It is not automatically clear, then, how sitagliptin should fit into diabetes treatment. The American Diabetes Association has not said in a definitive way how DPP-4 inhibitors should be used; it simply states that they may play a role in diabetes care. This is due to the relatively few studies done on sitagliptin compared with the wealth of information available for other drugs, as well as the newness of the data on sitagliptin.
Yet sitagliptin does have potential advantages over other drugs, as well as known disadvantages and side effects. One disadvantage is that compared with placebo, sitagliptin causes a small weight gain (about 1 pound on average). used in combination with metformin, however, it is associated with a loss of 5.5 pounds on average, compared with a gain of 2 pounds from the combination of metformin and glipizide.
Since sitagliptin is metabolized, or broken down, primarily by the kidneys and only metabolized by the liver to a small extent, the potential for it to interact with other drugs is relatively low; this finding has been confirmed in studies that have directly tested drug interactions in humans. However, this also means that the dose size of sitagliptin may need to be reduced for people in the later stages of kidney disease.