Initial Therapy With Janumet™ Provided Significantly Greater Blood Sugar Lowering Compared To Metformin Alone In Type 2 Diabetes

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

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New data presented at the American Diabetes Association (ADA) 69th Annual Scientific Sessions showed that initial treatment with 'Janumet'* (sitagliptin/metformin) provided significantly greater blood sugar improvements in drug-naïve** patients with type 2 diabetes, compared with metformin alone.[i]

"In this study, initial combination therapy with the fixed-dose combination sitagliptin and metformin for the treatment of type 2 diabetes helped patients achieve blood sugar goals more effectively than metformin alone," said Barry J. Goldstein, M.D., Ph.D., Vice President of Clinical Research, Diabetes and Obesity, Merck & Co., Inc.

Maintenance of combination therapy may not be appropriate for all patients. These management options are left to the discretion of the physician.

*Note, initial therapy with 'Janumet' is not currently licensed and the fixed-dose combination drug is not currently available in some countries, 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 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]

Initial therapy with a fixed dose sitagliptin and metformin*1

This large, randomised, double-blind study of initial therapy with a fixed dose combination of sitagliptin and metformin, compared to metformin alone, involved 1,250 drug-naïve patients** with a mean HbA1c*** baseline of 9.8 percent. Patients were randomized to sitagliptin/metformin (50/1,000 mg twice daily) or metformin (1,000 mg twice daily) for 44 weeks. The primary study hypotheses were addressed after 18 weeks. After 18 weeks, patients taking fixed dose combination of sitagliptin and metformin as initial therapy achieved mean HbA1c reductions from baseline of 2.4 percent (n=560), compared with 1.8 percent for patients taking metformin alone (n=566), a significant between-group difference of 0.6 percent (p<0.001).1

Significantly more patients taking fixed dose combination of sitagliptin and metformin as initial therapy achieved the International Diabetes Federation (IDF) goal of 6.5 percent, compared with patients taking metformin alone (32 percent vs. 16 percent, respectively; p<0.001). The primary efficacy endpoint of the study was HbA1c change from baseline at 18 weeks; 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 measurement.1

The incidence of overall clinical adverse experiences was similar in both groups. Prespecified adverse events of special interest included hypoglycaemia and selected gastrointestinal-related adverse experiences (abdominal pain, nausea, vomiting, and diahorrhea). In this study, the incidence of hypoglycaemia was not significantly different between the groups (2.1 percent for sitagliptin and metformin; 1.8 percent for metformin; p=0.686).1 Patients taking fixed dose combination of sitagliptin and metformin, compared to patients taking metformin alone, had significantly lower incidences of abdominal pain (1.1% vs. 3.8%, respectively; p=0.002) and diahorrhea (12.0% vs. 16.8%, respectively; p=0.015), with similar incidences of nausea (5.6% and 6.3%, respectively; p=0.622) and vomiting (2.9% and 2.6%, respectively; p=0.735). Patients in both groups experienced weight loss of 1.6 kg from baseline.1

About sitagliptin/metformin

The combination of sitagliptin, a DPP-4 inhibitor, and metformin, a mainstay of diabetes therapy is indicated as an adjunct to diet and exercise to improve glycaemic control in patients with type 2 diabetes inadequately controlled on diet and exercise plus metformin alone or those already being treated with the combination of sitagliptin and metformin. The drug combination is also indicated for use in combination with a sulfonylurea (SU) as an adjunct to diet and exercise in patients inadequately controlled on metformin and an SU. The dose of antihyperglycaemic therapy with sitagliptin/metformin should be individualised on the basis of the patient's current regimen, effectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100mg sitagliptin.3

Sitagliptin/metformin is contraindicated in patients with: hypersensitivity to the active substances or to any of the excipients; diabetic ketoacidosis or diabetic pre-coma; moderate and severe renal impairment or abnormal creatinine clearance, acute conditions with the potential to alter renal function; acute or chronic disease which may cause tissue hypoxia; hepatic impairment; acute alcohol intoxication; alcoholism and lactation. This drug combination should not be used in patients with type 1 diabetes.3

Patients taking sitagliptin/metformin in combination with a sulfonylurea, a medication known to cause hypoglycaemia, may be at a higher risk of hypoglycaemia to those patients taking sitagliptin/metformin alone. Therefore, a reduction in the dose of the sulfonylurea may be required.3

References

[i] Reasner C, Olansky L, Seck TL et al. Initial therapy with the fixed-dose combination of sitaglitptin and metformin (Janumet™) in patients with type 2 diabetes mellitus provides superior glycemic control and hemoglobin A1C goal attainment with lower rates of abdominal pain and diarrhea versus metformin alone. 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., Inc.

Source
Merck, Sharp & Dohme

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