Study Shows Combination Therapy With Januvia™ And Pioglitazone Offered Improved Blood Sugar-Lowering Efficacy Compared To Pioglitazone Alone

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

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New investigational data presented at the American Diabetes Association (ADA) 69th Annual Scientific Sessions showed that initial combination therapy with 'Januvia' (sitagliptin) and pioglitazone* substantially improved blood sugar control. [i]

"The results of this investigational study of sitagliptin as initial combination therapy with pioglitazone continues to extend the range of diabetes treatment regimens with which sitagliptin demonstrates significant blood sugar-lowering efficacy," said John Amatruda, M.D., SVP and Franchise Head, Diabetes and Obesity, Merck & Co., Inc. *Note, initial therapy with a combination of pioglitazone and sitagliptin is not currently licensed.

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 blood 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 initial combination therapy with sitagliptin and pioglitazone*1

A total of 497 patients with baseline HbA1c [1]* levels of 8.0 to 12.0 percent (mean baseline of 9.5 percent) received sitagliptin 100 mg once daily and pioglitazone 30 mg once daily or pioglitazone 30 mg once daily alone. The primary endpoint was HbA1c change from baseline at week 24. In this 24-week randomized, double-blind, placebo-controlled trial, initial treatment with sitagliptin and pioglitazone provided an HbA1c reduction of 2.4 percent from baseline (n=251) compared with 1.5 percent with pioglitazone alone (n=246), a between-group difference of 0.9 percent (p<0.001). Additionally, 38 percent of patients treated with sitagliptin and pioglitazone achieved the International Diabetes Federation (IDF) HbA1c goal of 6.5 percent at 24 weeks compared with 14 percent of patients given pioglitazone alone (p<0.001).1

The study also assessed changes in HbA1c based on patients' baseline HbA1c levels. Patients with a baseline HbA1c of 10.0 percent or more achieved a mean HbA1c reduction of 3.0 percent from baseline with sitagliptin and pioglitazone (n=99), compared with 2.1 percent for pioglitazone alone (n=88). Patients with a baseline HbA1c of less than 10.0 percent had an HbA1c reduction of 2.0 from baseline (n=152), compared with 1.1 percent for pioglitazone alone (n=158).1

Fasting plasma glucose (FPG) was significantly reduced (p<0.001) with sitagliptin in combination with pioglitazone (-63.0 mg/dL) compared to pioglitazone monotherapy (-40.2 mg/dL). Two hour postprandial glucose (PPG) was significantly reduced (p<0.001) with sitagliptin in combination with pioglitazone (113.6 mg/dL) compared to pioglitazone monotherapy (-68.9 mg/dL).1

Efficacy analyses were based on the full analysis set population, consisting of all randomised patients who received at least one dose of study treatment and who had both a baseline and at least one post-baseline measurement .1

Initial combination therapy with sitagliptin and pioglitazone demonstrated similar incidences of hypoglycaemia compared to pioglitazone alone (1.1 percent vs. 0.8 percent, respectively), gastrointestinal adverse events (5.7 percent vs. 6.9 percent, respectively), and oedema (2.7 percent vs. 3.5 percent, respectively). There was a larger mean increase from baseline in body weight in patients treated with sitagliptin plus pioglitazone than in those treated with pioglitazone alone (3.0 kg for the combination vs. 1.9 kg for pioglitazone, p=0.005).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] 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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