New Post-Hoc Analyses Show Januvia™ (sitagliptin) Provided Significant Blood Sugar Lowering Sustained Over Two Years

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

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New post-hoc analyses, presented at the American Diabetes Association (ADA) 69th Annual Scientific Sessions, of data pooled from studies of 104 weeks in duration showed 'Januvia' (sitagliptin), when taken alone* (2 studies) or in combination with metformin (2 studies), provided significant blood sugar lowering, which was sustained over two years.[i]

"These analyses show that, among patients who completed two years of follow up, sitagliptin maintained the mean HbA1c** levels at the goal of less than 7.0 percent," said Barry Goldstein, M.D., VP and Franchise Head, Diabetes and Obesity, Merck & Co., Inc. "It is encouraging to see data demonstrating sustained safety and efficacy of sitagliptin in patients with type 2 diabetes."

*Note, sitagliptin monotherapy is not currently licensed in the EU.

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]

Efficacy with Sitagliptin Over 2 Years*1

In a post-hoc pooled analysis of data from two clinical trials evaluating sitagliptin as monotherapy, HbA1c** over time was examined in 147 patients with a baseline HbA1c of 7.5 to 10.0 percent who were not taking any diabetes treatment at the screening visit. The mean HbA1c in the cohort of patients (n=32) completing two years of sitagliptin monotherapy decreased from a baseline of 8.3 to 6.9 percent.1

Because diabetes is a progressive disease, the studies had established criteria to specify when patients should start additional antihyperglycaemic therapy or discontinue from the studies, and these criteria became stricter over time. These criteria included measurements of fasting plasma glucose (FPG) and HbA1c. The post-hoc statistical analysis excluded data from patients who had missing HbA1c and after they had started additional medicines.1

Overall, 67 out of 147 patients (46%) in the monotherapy group received glycaemic rescue medication or discontinued treatment because patients did not meet the progressively stricter glycaemic criteria and/or did not meet the investigator's expectations of glycaemic improvement over the two years of study.1

Similarly, in a post-hoc pooled analysis of data from two clinical trials evaluating the addition of sitagliptin to metformin therapy, HbA1c over time was examined in 852 patients with a baseline HbA1c of 7.0 to 10.0 percent who were taking metformin only (>/=1500 mg/day) at the screening visit. The mean HbA1c in the group (n=347) completing two years of treatment with sitagliptin as add-on therapy decreased from a baseline of 7.7 to 6.9 percent.1

In this study, 283 out of 852 patients (33%) in the group that added sitagliptin to metformin received glycaemic rescue medication or discontinued treatment due to lack of efficacy (i.e. patients not meeting the progressively stricter, protocol-specified glycaemic criteria and/or not meeting the investigator's expectations of glycaemic improvement) over the 2 years.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. The drug 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. This medicine 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] Williams-Herman D., et al. Long-term Efficacy with Sitagliptin As Monotherapy or Add-on Therapy to Metformin: Improvement in Glycemic Control over 2 Years in Patients with Type 2 Diabetes. ADA poster, June 2009.

[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., Inc.

Source
Merck, Sharp & Dohme