Combination Tablet for Initial Therapy of Type 2 Diabetes

Sitagliptin/Metformin Combo Better than Each Agent Alone

By Jill Stein

CHICAGO—New data show that the combination sitagliptin and metformin agent (Janumet) is an effective first-line treatment for patients with type 2 diabetes, producing durable and significant glycemic improvement over 54 weeks with good tolerability.

"We saw both early and sustained glycemic response with the combination treatment," lead investigator Debora Williams-Herman, MD, senior director of clinical research at Merck Research Laboratories, Rahway, NJ, said at the American Diabetes Association annual meeting. "And the fact that the tolerability of the combination was good and sustained out to 54 weeks is new and significant information."

Janumet was approved by the FDA earlier this year as the first tablet combining a dipeptidyl peptidase-4 (DPP-4) inhibitor (sitagliptin; Januvia) and metformin (Glucophage) for the treatment of type 2 diabetes.

Dr Williams-Herman presented 54-week efficacy and safety results in patients who had completed a 24-week arm of the phase 3 trial evaluating initial combination therapy with sitagliptin and metformin in patients who had inadequate glycemic control on diet and exercise. Inadequate glycemic control was defined as a hemoglobin (Hb) A_1c level between 7.5% and 11.0%.

Diabetes Care.

In the initial phase of the study ( 2007;30:1979-1987), 1091 patients were randomized to 24 weeks of treatment with sitagliptin/metformin 100/2000 mg or 100/1000 mg; metformin 2000 or 1000 mg (all administered as divided doses, twice daily); sitagliptin 100 mg/day; or placebo.

After the 24-week placebo-controlled phase ended, 748 patients continued in a 30-week, double-blind, active-controlled arm. Results at 54 weeks showed that more patients achieved target HbA_1c levels with the combination tablet than with each agent alone (Table).

"Sitagliptin with metformin is one of the combinations of oral medications for diabetes?that does not cause hypoglycemia or low blood sugar reactions while at the same time helping to drive blood sugars toward the normal range," said Barry Goldstein, MD, PhD, director of the Division of Endocrinology, Diabetes and Metabolic Diseases at Jefferson Medical College, Philadelphia. "An advantage of the?combination is that it avoids this uncomfortable and even potentially dangerous side effect while achieving aggressive glucose targets in a majority of patients."

Table. Sitagliptin/metformin, combined or alone, for type 2 diabetes, 54 wk

Patient Outcomes

Sitagliptin/metformin, mg

Metformin, mg

Sitagliptin

100/2000

100/1000

2000

1000

100 mg

HbA_1c <7.0%, %

67

48

44

25

23

HbA_1c mean change

from baseline, %

-1.9

-1.7

-1.6

-1.2

-1.4

Note: All are daily dosages.