FDA Approvals: Janumet

[Admin]

April 12, 2007 — The US Food and Drug Administration (FDA) has approved sitagliptin plus metformin HCl tablets for use as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are not adequately controlled with either component alone or those already being treated with the drug combination.

Sitagliptin Plus Metformin HCl Tablets (Janumet) for Management of Type 2 Diabetes

On March 30, the FDA approved sitagliptin plus metformin HCl tablets (Janumet; Merck & Co Inc) for use with diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus who are inadequately controlled with either component alone or who are already receiving both components separately.

Sitagliptin is a dipeptidyl peptidase 4 (DPP-4) inhibitor and acts by increasing the body's active incretin hormone levels, thereby triggering the pancreas to increase insulin and signaling the liver to stop glucose production. Adding sitagliptin to an insulin sensitizer such as metformin therefore addresses the 3 key defects of type 2 diabetes: insulin resistance, ?-cell dysfunction, and ?-cell dysfunction.

Approval of the combination product was based on data from a 24-week double-blind study (n = 701) in which patients were randomized to receive add-on treatment with either 100 mg of sitagliptin (n = 453) or placebo (n = 224) after an initial run-in period of metformin monotherapy (minimum dosage, 1500 mg/day). Pioglitazone rescue was used for those who did not meet specific glycemic goals during the study.

Results showed that the addition of sitagliptin to metformin yielded significant improvements from baseline in mean hemoglobin A1c levels (-0.7% vs -0.0%; change = -0.7%; 95% confidence interval [CI], -0.8% to -0.5%; P < .001). In the study, more than twice as many patients receiving sitagliptin add-on therapy achieved a hemoglobin A1c goal of less than 7% compared with those receiving metformin alone (47% vs 18%; P < .001).

Use of the combination product also provided 24-hour glucose response, as demonstrated by significant improvements in fasting plasma glucose (-17 vs +9 mg/dL; change = -25 mg/dL; 95% CI, -31 to -20 mg/dL) and 2-hour postprandial glucose levels (-62 vs -11 mg/dL; change = -51 mg/dL; 95% CI, -61 to -41 mg/dL), compared with metformin alone (P < .001, both). Rescue glycemic therapy was required only by 5% of patients receiving sitagliptin plus metformin compared with 14% of those receiving metformin alone.

Use of sitagliptin plus metformin was associated with mean weight loss from baseline similar to that of metformin monotherapy (1.5 vs 1.3 lb), with no increased risks for hypoglycemia (1.3% vs 2.1%), edema (0.9% vs 1.3%), or gastrointestinal (GI) adverse events (11.6% vs 9.7%). Adverse GI events included diarrhea (2.4% vs 2.5%), abdominal pain (2.2% vs 3.8%), nausea (1.3% vs 0.8%), and vomiting (1.1% vs 0.8%). The most commonly reported adverse event occurring with an incidence of 5% or greater in the sitagliptin/metformin group compared with those receiving metformin alone was nasopharyngitis.

Sitagliptin/metformin tablets are available in 50-mg/500-mg and 50-mg/1000-mg formulations and generally should be administered twice daily with meals. Individualized dosing is recommended based on the patient's current regimen, efficacy, and tolerability; gradual dose escalation is recommended to reduce the GI effects of metformin. Daily doses should not exceed 100 mg of sitagliptin and 2000 mg of metformin.

For patients inadequately controlled with metformin alone, the usual starting dosage of the combination product should be 50 mg of sitagliptin twice daily plus the usual metformin dose. Those receiving 850 mg of metformin twice daily initially should receive 50 mg of sitagliptin and 1000 mg of metformin twice daily.

Patients who are inadequately controlled with sitagliptin alone should receive an initial dosage of 50 mg of sitagliptin and 500 mg of metformin twice daily and then titrated up to 50 mg of sitagliptin and 1000 mg of metformin twice daily as needed. Those taking sitagliptin monotherapy that has been dose-adjusted for renal insufficiency should not receive the combination product.

Because both sitagliptin and metformin are substantially excreted by the kidneys and metformin accumulation is linked to an increasing risk for lactic acidosis, the combination product is contraindicated in patients with renal disease/dysfunction (serum creatinine levels ? 1.5 mg/dL [men] or ? 1.4 mg/dL [women]) or abnormal creatinine clearance secondary to shock, acute myocardial infarction, and septicemia.

The FDA advises that renal function be assessed and verified as normal prior to initiation of sitagliptin/metformin therapy and at least annually thereafter; increased testing frequency is advised for elderly patients and others at increased risk for renal impairment. Cationic drugs (eg, amiodarone, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin) that are eliminated by renal tubular secretion should be used with caution because of their potential interference with metformin clearance.

Because of the risk for acute alteration of renal function associated with intravascular administration of iodinated contrast materials, sitagliptin/metformin should be discontinued temporarily in patients undergoing certain radiologic studies.

Sitagliptin/metformin therapy also should be avoided in patients with clinical or laboratory evidence of hepatic disease because impaired hepatic function can significantly limit the ability to clear lactate. The FDA notes that whereas the reported incidence of lactic acidosis in metformin-treated patients is low (about 0.03 cases/1000 patient-years), the associated mortality rate is approximately 50% (about 0.015 fatal cases/1000 patient-years). For patients with the condition, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin.

Sitagliptin 25-, 50-, and 100-mg tablets (Januvia; Merck & Co Inc) previously were approved by the FDA for use with diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus; they can be used as monotherapy or in combination with metformin or thiazolidinediones if additional control is required.

http://www.fda.gov/cder/foi/label/2007/022044lbl.pdf

[Love]

April 12, 2007 — The US Food and Drug Administration (FDA) has approved sitagliptin plus metformin HCl tablets for use as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are not adequately controlled with either component alone or those already being treated with the drug combination.

Sitagliptin Plus Metformin HCl Tablets (Janumet) for Management of Type 2 Diabetes

On March 30, the FDA approved sitagliptin plus metformin HCl tablets (Janumet; Merck & Co Inc) for use with diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus who are inadequately controlled with either component alone or who are already receiving both components separately.

Sitagliptin is a dipeptidyl peptidase 4 (DPP-4) inhibitor and acts by increasing the body's active incretin hormone levels, thereby triggering the pancreas to increase insulin and signaling the liver to stop glucose production. Adding sitagliptin to an insulin sensitizer such as metformin therefore addresses the 3 key defects of type 2 diabetes: insulin resistance, ?-cell dysfunction, and ?-cell dysfunction.

Approval of the combination product was based on data from a 24-week double-blind study (n = 701) in which patients were randomized to receive add-on treatment with either 100 mg of sitagliptin (n = 453) or placebo (n = 224) after an initial run-in period of metformin monotherapy (minimum dosage, 1500 mg/day). Pioglitazone rescue was used for those who did not meet specific glycemic goals during the study.

Results showed that the addition of sitagliptin to metformin yielded significant improvements from baseline in mean hemoglobin A1c levels (-0.7% vs -0.0%; change = -0.7%; 95% confidence interval [CI], -0.8% to -0.5%; P < .001). In the study, more than twice as many patients receiving sitagliptin add-on therapy achieved a hemoglobin A1c goal of less than 7% compared with those receiving metformin alone (47% vs 18%; P < .001).

Use of the combination product also provided 24-hour glucose response, as demonstrated by significant improvements in fasting plasma glucose (-17 vs +9 mg/dL; change = -25 mg/dL; 95% CI, -31 to -20 mg/dL) and 2-hour postprandial glucose levels (-62 vs -11 mg/dL; change = -51 mg/dL; 95% CI, -61 to -41 mg/dL), compared with metformin alone (P < .001, both). Rescue glycemic therapy was required only by 5% of patients receiving sitagliptin plus metformin compared with 14% of those receiving metformin alone.

Use of sitagliptin plus metformin was associated with mean weight loss from baseline similar to that of metformin monotherapy (1.5 vs 1.3 lb), with no increased risks for hypoglycemia (1.3% vs 2.1%), edema (0.9% vs 1.3%), or gastrointestinal (GI) adverse events (11.6% vs 9.7%). Adverse GI events included diarrhea (2.4% vs 2.5%), abdominal pain (2.2% vs 3.8%), nausea (1.3% vs 0.8%), and vomiting (1.1% vs 0.8%). The most commonly reported adverse event occurring with an incidence of 5% or greater in the sitagliptin/metformin group compared with those receiving metformin alone was nasopharyngitis.

Sitagliptin/metformin tablets are available in 50-mg/500-mg and 50-mg/1000-mg formulations and generally should be administered twice daily with meals. Individualized dosing is recommended based on the patient's current regimen, efficacy, and tolerability; gradual dose escalation is recommended to reduce the GI effects of metformin. Daily doses should not exceed 100 mg of sitagliptin and 2000 mg of metformin.

For patients inadequately controlled with metformin alone, the usual starting dosage of the combination product should be 50 mg of sitagliptin twice daily plus the usual metformin dose. Those receiving 850 mg of metformin twice daily initially should receive 50 mg of sitagliptin and 1000 mg of metformin twice daily.

Patients who are inadequately controlled with sitagliptin alone should receive an initial dosage of 50 mg of sitagliptin and 500 mg of metformin twice daily and then titrated up to 50 mg of sitagliptin and 1000 mg of metformin twice daily as needed. Those taking sitagliptin monotherapy that has been dose-adjusted for renal insufficiency should not receive the combination product.

Because both sitagliptin and metformin are substantially excreted by the kidneys and metformin accumulation is linked to an increasing risk for lactic acidosis, the combination product is contraindicated in patients with renal disease/dysfunction (serum creatinine levels ? 1.5 mg/dL [men] or ? 1.4 mg/dL [women]) or abnormal creatinine clearance secondary to shock, acute myocardial infarction, and septicemia.

The FDA advises that renal function be assessed and verified as normal prior to initiation of sitagliptin/metformin therapy and at least annually thereafter; increased testing frequency is advised for elderly patients and others at increased risk for renal impairment. Cationic drugs (eg, amiodarone, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin) that are eliminated by renal tubular secretion should be used with caution because of their potential interference with metformin clearance.

Because of the risk for acute alteration of renal function associated with intravascular administration of iodinated contrast materials, sitagliptin/metformin should be discontinued temporarily in patients undergoing certain radiologic studies.

Sitagliptin/metformin therapy also should be avoided in patients with clinical or laboratory evidence of hepatic disease because impaired hepatic function can significantly limit the ability to clear lactate. The FDA notes that whereas the reported incidence of lactic acidosis in metformin-treated patients is low (about 0.03 cases/1000 patient-years), the associated mortality rate is approximately 50% (about 0.015 fatal cases/1000 patient-years). For patients with the condition, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin.

Sitagliptin 25-, 50-, and 100-mg tablets (Januvia; Merck & Co Inc) previously were approved by the FDA for use with diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus; they can be used as monotherapy or in combination with metformin or thiazolidinediones if additional control is required.

http://www.fda.gov/cder/foi/label/2007/022044lbl.pdf

Hi i have been doing some research on this drug and comparing it to acomplia for weight loss, we are going to study the results on 14 patients, 7 taking each drug for 6 months and are going to monitor the success. I will post back my results. THanks for the article.

[drbalo]

Interesting! Hope to see the result of your study soon! Please remember to post. 

[John flower]

I would have titled this"Fenny Pharmacy you're On Notice"but i decided on a generic title instead.


Fenny pharmacy in case your are wondering is on Newark Avenue between Barrow and Grove street.It was Carry Drugs for quite some time until it was purchased last year by a new owner.

Last fall i purchased a pregnancy test form them only to find out that it was expired( i returned it and got my money back.).My wife went there last night to buy Tums and they had an expiration date of June 2006.Since we have only been to Fenny Pharmacy twice, and both times the products we wanted were expired, I can only guess that many of their products are past their due date.


http://www.drugdelivery.ca/

[fioricetlive]

IT is a very useful information. I have read it very carefully and thank you for it.

[naturalimmunity]

"Love" still didn't post the results of his research!