Sun Pharma's Dapagliflozin, Glimepiride, Metformin FDC Fails to Secure CDSCO Panel Nod Over Safety, Utility Concerns
New Delhi: Expressing doubts over the clinical utility of administering such a small dose of Glimepiride once daily, especially considering over the adverse events linked with the proposed combination presented by Sun Pharma Laboratories, the Subject Expert Committee (SEC) functional under the Central Drugs Standard Control Organization (CDSCO) has denied the approval of the proposed antidiabetic fixed dose combination (FDC) of Dapagliflozin Propanediol eq. to Dapagliflozin 10 mg/10 mg plus Glimepiride IP 0.5 mg/0.5 mg plus Metformin Hydrochloride IP (extended release) 500 mg/1000 mg film coated tablet.
This came after the drug major Sun Pharma Laboratories presented the proposal, along with justification for bioequivalence (BE) and Phase III clinical trial (CT) waiver before the committee.
Dapagliflozin inhibits the sodium-glucose cotransporter 2(SGLT2), which is primarily located in the proximal tubule of the nephron. SGLT2 facilitates 90% of glucose reabsorption in the kidneys, and so its inhibition allows for glucose to be excreted in the urine. This excretion allows for better glycemic control and potentially weight loss in patients with type 2 diabetes mellitus.
Glimepiride is a sulfonylurea drug used to treat type 2 diabetes mellitus. Glimepiride stimulates the secretion of insulin granules from the pancreatic beta cells and improves the sensitivity of peripheral tissues to insulin to increase peripheral glucose uptake, thus reducing plasma blood glucose levels and glycated hemoglobin (HbA1C) levels.
Metformin is a biguanide antihyperglycemic used in conjunction with diet and exercise for glycemic control in type 2 diabetes mellitus. Metformin reduces hepatic production of glucose, decreases the intestinal absorption of glucose, and enhances insulin sensitivity by increasing both peripheral glucose uptake and utilization.
At the recent SEC meeting for endocrinology and metabolism, the expert panel reviewed the proposal presented by the drug major Sun Pharma Laboratories for an antidiabetic fixed dose combination of Dapagliflozin Propanediol eq. to Dapagliflozin 10 mg/10 mg plus Glimepiride IP 0.5 mg/0.5 mg plus Metformin Hydrochloride IP (ER) 500 mg/1000 mg film-coated tablet along with the justification for bioequivalence (BE) and Phase III clinical trial (CT) waiver.
Following a thorough discussion, the committee opined, "Utility of this small dose of Glimepiride once daily, considering the Adverse Events of this combination, is questionable."
Hence, in line with the above, the committee did not recommend approval of the proposed fixed-dose combination (FDC).
