Study Shows Januvia(TM) (sitagliptin) Offered Significant Blood Sugar-Lowering Efficacy In Combination With Insulin In Type 2 Diabetes

Main Category: Diabetes
Article Date: 11 Jun 2009 - 3:00 PDT

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A new investigational study presented at the American Diabetes Association (ADA) 69th Annual Scientific Sessions showed that 'Januvia' (sitagliptin), when added to ongoing insulin therapy with or without metformin, significantly improved blood sugar control.[i] Applications to use 'Januvia' and 'Janumet'* (sitagliptin/metformin) in combination with insulin have been accepted for review by the European Medicines Agency (EMEA) and by the U.S. Food and Drug Administration (FDA) and are currently under review.

"Due to the progressive nature of the disease, over time most type 2 diabetes patients require multiple drugs to achieve glycemic control," said John Amatruda, M.D., Senior Vice President and Franchise Head, Diabetes and Obesity, Merck & Co., Inc. "If approved for use with insulin, sitagliptin and the fixed-dose combination of sitagliptin and metformin will be additional options for patients with type 2 diabetes who are taking insulin and whose blood sugar is not at goal."

* Note, 'Janumet' is not available in some countries yet, such as the UK.

Sitagliptin is a highly selective, once-daily DPP-4 inhibitor that enhances a natural body system called the incretin system, to help regulate blood sugar by increasing levels of active GLP-1 and GIP hormones; it inhibits DPP-4 over 24 hours.[ii] The fixed dose combination of sitagliptin and metformin targets all three key defects of diabetes: insulin deficiency from pancreatic beta cells, insulin resistance, and overproduction of glucose by the liver.[iii] Sitagliptin is the first approved medicine in the DPP-4 inhibitor class of oral treatments. It has been approved in over 80 countries and to-date, there have been more than 11.1 million prescriptions dispensed worldwide.[iv]

Study of addition of sitagliptin to ongoing insulin therapy with or without metformin1

In a 24-week study of 564 patients on long-acting, intermediate-acting or pre-mixed insulin, with or without metformin, the addition of sitagliptin (n=281) reduced HbA1c** by 0.6 percent (p<0.001) relative to placebo (n=283) from a mean baseline HbA1c of 8.7 percent (mean change from baseline -0.6 percent with sitagliptin, 0.0 percent with placebo). Additionally, 13 percent of patients taking sitagliptin with insulin therapy achieved the American Diabetes Association HbA1c goal of less than 7.0 percent compared to 5 percent of patients taking placebo (p<0.001). The addition of sitagliptin also significantly (p<0.001) reduced fasting plasma glucose (FPG) by 0.8 mmol/L (-15.0 mg/dl) and 2-hour postprandial glucose (PPG) by 2.0 mmol/L (-36.1 mg/dl) versus placebo.1

The primary efficacy endpoint of the study was change in HbA1c from baseline; analyses were based on all patients who received at least one dose of study treatment and who had both a baseline and at least one post-baseline HbA1c measurement.1

A higher incidence of adverse events was reported with the addition of sitagliptin compared to placebo due mainly to an increased incidence of hypoglycaemia (15.5 percent vs. 7.8 percent, respectively). The incidence of severe hypoglycaemic events was 0.6 percent with sitagliptin vs. 0.3 percent with placebo. There was no change from baseline in body weight in either treatment group.1

About sitagliptin

Sitagliptin is a member of a class of oral anti-hyperglycaemic agents called dipeptidyl peptidase 4 (DPP-4) inhibitors and is licensed for the treatment of type 2 diabetes in combination with either metformin and/or a sulphonylurea, or in certain patients, with a PPARy agonist (i.e. thiazolidinedione), when diet and exercise plus the other agent(s) do not provide adequate glycaemic control. Sitagliptin enhances the body's own ability to lower blood sugar levels by increasing the levels of the body's own active incretins, called GLP-1 and GIP. 2

The recommended dose of sitagliptin is 100mg once daily, with or without food, for all approved indications.2

Sitagliptin should not be used in patients with moderate or severe renal impairment or in patients with hepatic insufficiency and is contraindicated in patients with hypersensitivity to the active substances or to any of the excipients. The drug should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, or in woman who are lactating or pregnant. 2

References

[i] Vilsboll T, Rosenstock JM, Yki-Jarvinen H et al. Sitagliptin, a selective DPP-4 inhibitor, improves glycemic control when added to insulin, with or without metformin, in patients with type 2 diabetes. Data presented at ADA Congress 2009, New Orleans

[ii] JANUVIA European Public Assessment Report (EPAR), Product Information, 19/09/2008 Januvia-H-C-722-N-06

[iii] JANUMET European Public Assessment Report (EPAR), Product Information, 10/12/2008 Janumet BMS-H-C-861-IA-05.

[iv] IMS Health, NPA™ Weekly, TRxs, week-ending October 20, 2006 through week-ending May 22, 2009 Data on file, Merck & Co

Source
Merck, Sharp & Dohme

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