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Formulation comprising Metformin in combination with DPP-4 inhibitors Disclosure Number: IPCOM000241112D
Publication Date: 2015-Mar-27
Document File: 6 page(s) / 52K

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Formulation comprising Metformin in combination with DPP-4 inhibitors

Diabetes mellitus, commonly referred to as diabetes, is a group of metabolic diseases in which there are high blood sugar levels over a prolonged period. Diabetes is due to either the pancreas not producing enough insulin or the cells of the body not responding properly to the insulin produced.

There are three main types:

  • Type 1: results from the body's failure to produce enough insulin.
  • Type 2: begins with insulin resistance, a condition in which cells fail to respond to insulin properly. As the disease progresses a lack of insulin may also develop.
  • Gestational diabetes: occurs when pregnant women without a previous history of diabetes develop a high blood glucose level.

Rates of Type 2 diabetes have increased markedly since 1960 in parallel with obesity. As of 2010 there were approximately 285 million people diagnosed with the disease compared to around 30 million in 1985.

There are several classes of anti-diabetic medications available. Metformin is generally recommended as a first line treatment as there is some evidence that it decreases mortality. It has an oral bioavailability of 50–60% under fasting conditions, and is absorbed slowly. Peak plasma concentrations (Cmax) are reached within one to three hours of taking immediate-release Metformin and four to eight hours with extended-release formulations. It is not metabolized and is cleared from the body by tubular secretion and excreted unchanged in the urine.

A second oral agent of another class may be used if Metformin is not sufficient. Other classes of medications include: sulfonylureas, nonsulfonylurea secretagogues, a-glucosidase inhibitors, thiazolidinediones, glucagon-like peptide-1 analog and dipeptidyl peptidase-4 inhibitors.

Inhibition of dipeptidyl peptidase 4 (DPP-4) is a novel treatment for Type 2 diabetes. DPP-4 inhibition prevents the inactivation of glucagon-like peptide 1 (GLP-1), which increases levels of active GLP-1. This increases insulin secretion and reduces glucagon secretion, thereby lowering glucose levels.

Drugs belonging to the class of DPP-4 inhibitors are:

  • Sitagliptin
  • Vildagliptin
  • Saxagliptin
  • Linagliptin
  • Anagliptin
  • Teneligliptin
  • Alogliptin
  • Gemigliptin
  • Dutogliptin

These are orally active compounds with a long duration, allowing once-daily administration. They improve metabolic control in Type 2 diabetes, both in monotherapy and in combination with Metformin and thiazolidinediones.

Sitagliptin was approved by the FDA on October 17, 2006, and is marketed in the US as Januvia® by Merck & Co. On April 2, 2007, the FDA approved an oral combination of Sitagliptin and Metformin marketed in the US as Janumet®.

Vildagliptin has not been approved by the FDA but is marketed in Europe as Galvus® by Novartis. The combination of Vildagliptin and Metformin is marketed for example as Eucreas® or Galvumet®.

In the following, the preparation of formulations comprising Metformin in combination with d...