(95 % CI)
 
Sitagliptin 100 mg once daily added to ongoing metformin therapy%

(N=453)

8.0

-0.7†
 -0.7†‡

(-0.8, -0.5)
 
Sitagliptin 100 mg once daily added to ongoing glimepiride + metformin therapy%

(N=115)

8.3

-0.6†
 -0.9†‡

(-1.1, -0.7)
 
Sitagliptin 100 mg once daily added to ongoing rosiglitazone + metformin therapy (N=170)

Week 18

Week 54
 
8.8

8.8

-1.0†

-1.0†
 

-0.7†‡

(-0.9, -0.5)

-0.8

(-1.0, -0.5)
 
Sitagliptin 100 mg once daily added to ongoing insulin + metformin therapy %

(N=223)
 
8.7
 
-0.7
 -0.5

(-0.7, -0.4)
 
Initial Therapy (twice daily)%:

Sitagliptin 50 mg + metformin 500 mg

(N=183)
 
8.8

-1.4†
 -1.6†‡

(-1.8, -1.3)
 
Initial Therapy (twice daily)%:

Sitagliptin 50 mg + metformin 1,000 mg

(N=178)
 

8.8
 

-1.9†
 -2.1†‡

(-2.3, -1.8)
 

* All Patients Treated Population (an intention-to-treat analysis).

Least squares means adjusted for prior antihyperglycaemic therapy status and baseline value.

p< 0.001 compared to placebo or placebo + combination treatment.

HbA1c (%) at week 24.

Least squares mean adjusted for insulin use at Visit 1 (pre-mixed vs. non-pre-mixed [intermediate- or long-acting]), and baseline value.

In a 52-week study, comparing the efficacy and safety of the addition of sitagliptin 100 mg once daily or glipizide (a sulphonylurea agent) in patients with inadequate glycaemic control on metformin monotherapy, sitagliptin was similar to glipizide in reducing HbA1c (-0.7 % mean change from baselines at week 52, with baseline HbA1c of approximately 7.5 % in both groups). The mean glipizide dose used in the comparator group was 10 mg per day with approximately 40 % of patients requiring a glipizide dose of  5 mg/day throughout the study. However, more patients in the sitagliptin group discontinued due to lack of efficacy than in the glipizide group. Patients treated with sitagliptin exhibited a significant mean decrease from baseline in body weight (-1.5 kg) compared to a significant weight gain in patients administered glipizide (+1.1 kg). In this study, the proinsulin to insulin ratio, a marker of efficiency of insulin synthesis and release, improved with sitagliptin and deteriorated with glipizide treatment. The incidence of hypoglycaemia in the sitagliptin group (4.9 %) was significantly lower than that in the glipizide group (32.0 %).

Metformin

Metformin is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose. It does not stimulate insulin secretion and therefore does not produce hypoglycaemia.

Metformin may act via three mechanisms:

- by reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis

- in muscle, by modestly increasing insulin sensitivity, improving peripheral glucose uptake and utilisation

- by delaying intestinal glucose absorption

Metformin stimulates intracellular glycogen synthesis by acting on gl