New One-Year Data Show Investigational Use of Initial Combination Therapy with Sitagliptin and Metformin Significantly Improves Blood Glucose Control in Patients with Type 2 Diabetes Compared With Metformin Alone

- Additional Data Offer Insight into Complementary Effect of Sitagliptin and Metformin on Blood Glucose Levels -

Initial combination therapy with sitagliptin and metformin provides significant and sustained improvement in blood sugar control compared to metformin alone, over a one-year period.1a Up to 67% of patients¨ with type 2 diabetes on sitagliptin and metformin initial combination therapy achieved an HbA1c of <7% at 54 weeks, compared to only 44% on metformin alone, according to new data presented at the 43rd Annual Meeting of the European Association for the Study of Diabetes (EASD). 1b

The study demonstrated a mean HbA1c reduction from baseline of 1.8% in patients treated with the initial combination of sitagliptin 50mg/metformin 1000mg twice daily. 1c Mean HbA1c reductions from baseline were 1.4% in patients treated with sitagliptin 50mg/metformin 500mg twice daily, 1.3% in patients treated with metformin 1000mg twice daily, 1.0% in patients treated with metformin 500mg twice daily, and 0.8% in patients treated with sitagliptin 100mg once daily for up to 54 weeks.1d  

A patient’s starting HbA1c level is an important predictive factor of the magnitude of HbA1c reduction in response to anti-hyperglycaemic therapy.  In a subgroup analysis of patients grouped by severity of HbA1c at baseline, treatment with sitagliptin 50mg/metformin 1000mg twice daily demonstrated larger mean HbA1c reductions from baseline with higher baseline HbA1c.1e A mean reduction of 3.1% was seen in patients with baseline HbA1c of 10% or more, while reductions of 2.2%, 1.7%, and 1.0% were seen with baseline HbA1c values of ≥9 to <10%, ≥8 to <9%, and <8%, respectively.1f

The incidence of hypoglycemia (1.1%-2.7%) was low across treatment groups. The incidences of gastrointestinal adverse experiences were similar for the combination groups compared with the respective metformin monotherapy groups.1g

Professor Anthony Barnett, Professor of Medicine, Birmingham Heartlands & Solihull NHS Trust, comments: “In the UK many patients with type 2 diabetes remain above the recommended HbA1c level. These investigational data are promising, showing sustained glycaemic improvements up to one year, including in the most severe patients. The study provides additional evidence to show that sitagliptin is an effective and well-tolerated treatment.”

[This study examined the investigational use of initial combined sitagliptin and metformin therapy in type 2 diabetes. Sitagliptin is not currently approved for initial combination use with metformin in the UK.2a Since metformin is administered twice daily, in this study sitagliptin was given as 50 mg twice daily to allow for co-administration of the two treatments. The UK approved dose for sitagliptin is 100mg once daily.]

Sitagliptin, a Selective DPP-4 Inhibitor, and Metformin have Complementary Effects to Increase Active GLP-1 Concentrations3a

Data from a separate study revealed that the different mechanisms of action of sitagliptin and metformin, when used in combination in healthy adults, have a complementary effect on levels of glucagon-like peptide-1 (GLP-1).3b This aspect of the mechanism of action of metformin used in combination with sitagliptin was previously unknown.

A randomised, placebo-controlled, double-blind, 4-period crossover study was conducted in 16 healthy adults.3c In each 2-day treatment period, subjects received one of four treatments;  once-daily sitagliptin 100mg, twice-daily metformin 500mg, co-administration of sitagliptin and metformin, or placebo.3d  

When taken separately, sitagliptin and metformin increased overall post-meal active GLP-1 levels by 1.95- and 1.76-fold respectively (p<0.001) compared with placebo.3e When administered together, sitagliptin and metformin increased active GLP-1 levels by 4.12-fold (p<0.001) compared with placebo.3f  

In contrast to active GLP-1 levels, which were increased by both drugs, the levels of total GLP-1 (both active and inactive GLP-1) were increased by metformin only and not by sitagliptin.3gActive GIP concentrations increased with sitagliptin, and sitagliptin plus metformin, but were unchanged with metformin alone.3h

These observations are consistent with the effect of sitagliptin on raising active GLP-1 levels by reducing its clearance, and suggest that metformin acts in a different manner to increase active GLP-1 levels.3i This study provides evidence that the two drugs may have complementary effects on GLP-1.3j

GLP-1 plays an important role in regulating the body’s blood sugar levels.  When food is consumed, GLP-1 is released by the gastrointestinal tract to stimulate the pancreatic beta cells to secrete insulin, a hormone that helps the body to use glucose for energy.  GLP-1 also suppresses the release of glucagon from the pancreatic alpha cells, which, in turn, signals the liver to reduce its production of sugar.

Sitagliptin is the first DPP-4 inhibitor available in the United Kingdom, currently licensed as an add-on therapy to metformin or a thiazolidinedione, in patients with type 2 diabetes when the single agent alone plus diet and exercise do not provide adequate glycaemic control.2b

– ENDS –

For further information, please contact:


Francesca McNeil

Cohn & Wolfe
Office: 020 7331 5350
Francesca_McNeil@uk.cohnwolfe.com

Georgie Griffith
Office: 020 7331 5369
Mob: 07813 158025
Georgie_griffith@uk.cohnwolfe.com   

Louise Barr (on site)
Merck Sharp & Dohme Limited
Mob: 07974 444 495
louise_barr@merck.com

Helen Wright (office)
Office: 01992 452550
helen_wright@merck.com

¨ 50.4% of the 1,091 patients in the study were treatment-naïve, while 49.6% had received previous mono- or combination therapy with oral anti-hyperglycaemic agents.

Notes to Editors
This press release contains "forward-looking statements" about product development, product potential or about financial performance based on current expectations of the management of Merck & Co., Inc.  No forward-looking statement can be guaranteed, and actual results may differ materially from those projected.  Merck & Co., Inc. undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.

For UK full prescribing information, including Clinical Particulars and Pharmacological Properties, please refer to the Summary of Product Characteristics accompanying this press release.  If the SPC is missing, please contact any of the individuals listed at the end of this release for a copy.

'Januvia'® is a Registered Trademark of Merck & Co., Inc., Whitehouse Station, New Jersey, USA.

Merck Sharp & Dohme Limited (MSD) is the UK subsidiary of Merck & Co., Inc., of Whitehouse Station, New Jersey, USA, a leading research-based pharmaceutical company that discovers, develops, manufactures and markets a wide range of innovative pharmaceutical products to improve human health.

References:

1.  Williams-Herman D., Johnson J., Lunceford J.  Initial combination therapy with sitagliptin and metformin provides effective and durable glycaemic control over 1 year in patients with type 2 diabetes (T2DM): A pivotal Phase III clinical trial. (Abstract number #0113). Presented at the 43rd Annual Meeting of the European Association for the Study of Diabetes (EASD) 2007, Amsterdam, Netherlands.

2.  'Januvia' (sitagliptin). Summary of Product Characteristics. MSD UK, 2007

3.  Migoya E., Miller J., Larson P. et al. Sitagliptin, a selective DPP-4 inhibitor, and metformin have complementary effects to increase active GLP-1 concentrations. (Abstract number #0111). Presented at the 43rd Annual Meeting of the European Association for the Study of Diabetes (EASD) 2007, Amsterdam, Netherlands.

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