Sitagliptin+Metformin Effective in Type 2 Diabetes

Mean HbA1c change from baseline was -2.9%, for patients with an HbA1c value greater than 11%. Initial combination therapy with sitagliptin and metformin is effective in improving glycemic control in patients with type 2 diabetes mellitus, according to the results of a study.

 "Initial antihyperglycemic monotherapy is often unsuccessful at getting patients with type 2 diabetes to glycemic goals, and as the glycemic targets recommended by standard guidelines are lowered, even fewer patients will achieve the goal with single agent treatment," write Barry J. Goldstein, MD, PhD, from the Jefferson Medical College in Philadelphia, Pennsylvania, from the Sitagliptin 036 Study Group. "Sitagliptin, an oral and highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, represents a novel therapeutic approach for the treatment of patients with type 2 diabetes…. Since sitagliptin and metformin lower glucose concentrations through different, but potentially complementary mechanisms, the initial combination of sitagliptin and metformin should provide effective, potentially additive, glycemic control."

The objective of this 24-week, placebo-controlled, parallel-group study was to evaluate the efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes mellitus and inadequate glycemic control with diet and exercise.

In this double-blind trial, 1091 patients with type 2 diabetes mellitus and HbA1c values of 7.5% to 11% were randomized to 1 of 6 daily treatments: 100 mg of sitagliptin and 1000 mg of metformin (S100/M1000), 100 mg of sitagliptin and 2000 mg of metformin (S100/M2000), 1000 mg of metformin (M1000), 2000 mg of metformin (M2000; all as divided doses administered twice daily), 100 mg of sitagliptin every day (S100), or placebo.

In the randomized patients, the mean baseline HbA1c value was 8.8%. The placebo-subtracted HbA1c change from baseline was -2.07% (S100/M2000), -1.57% (S100/M1000), -1.30% (M2000), -0.99% (M1000), and -0.83% (S100; P < .001 for comparisons vs placebo and for coadministration vs respective monotherapies). In the S100/M2000 group, the proportion of patients who achieved HbA1c values less than 7% and less than 6.5% was 66% and 44%, respectively (P < .001 vs S100 or M2000).

In the open-label cohort treated with S100/M2000, the within-group mean HbA1c change from baseline was -2.9%. The incidence of hypoglycemia was low (0.5% – 2.2%) across active treatment groups and was not significantly different from that seen in the placebo group (0.6%). The incidence of gastrointestinal adverse experiences was similar for coadministration therapies compared with their respective metformin monotherapies.

"The initial combination of sitagliptin and metformin provided substantial and additive glycemic improvement and was generally well-tolerated in patients with T2DM," the authors write. "As with other antihyperglycemic agents including sitagliptin, patients with more severe baseline hyperglycemia (ie, HbA1c value ≥ 9%) had the largest reductions with coadministration of sitagliptin and metformin."

Practice Pearls

• In adults with type 2 diabetes mellitus who have inadequate glycemic control with diet and exercise regimens, initial sitagliptin and metformin combination therapy results in greater improvement in HbA1c and greater incidence of HbA1c values less than 7% over time and vs monotherapy.
• Sitagliptin and metformin combination therapy has similar incidence of adverse effects vs metformin monotherapy and low incidence of hypoglycemia in patients with type 2 diabetes mellitus. High-dose metformin combination or monotherapy is associated with gastrointestinal adverse effects.

Diabetes Care. Published online May 7, 2007.

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