Compositions and methods for treating metabolic disorders
Inventors
Baron, Alain D. • Fineman, Mark S. • Beeley, Nigel R. A.
Assignees
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Publication Number
US-11974971-B2
Publication Date
2024-05-07
Expiration Date
Abstract
Methods for improving the gastrointestinal tolerability of biguanide compounds and for treating metabolic disorders and/or inducing weight loss in patients in need thereof, particularly in individuals having a contraindication for treatment with biguanide compounds, are provided comprising administering delayed release formulations of such biguanide compounds, including metformin, targeted to the small intestine.
Core Innovation
The invention relates to treating a metabolic disorder in a patient having a condition that contraindicates treatment with a biguanide compound by administering an oral delayed-release formulation of a biguanide compound selected from metformin, phenformin, buformin, or imeglimin, or a salt thereof. The delayed-release formulation releases the biguanide compound downstream of duodenum to one or more regions of intestine.
The metabolic disorder comprises a hyperglycemic condition, a disorder of lipid metabolism, or both a hyperglycemic condition and a disorder of lipid metabolism. The delayed-release formulation has bioavailability no more than 80% of the bioavailability of the biguanide compound in an immediate-release composition having the same amount of biguanide compound.
The resulting circulating plasma concentration of the biguanide compound is below about 1 µg/mL. The contraindicating condition is a gastrointestinal condition caused by biguanide administration, wherein the gastrointestinal condition is nausea, vomiting, or dyspepsia, or is dizziness, headache, or renal impairment.
Claims Coverage
The claim coverage includes one independent claim with four inventive features.
Downstream-of-duodenum oral delayed-release biguanide formulation
Administering an oral delayed-release formulation of a biguanide compound selected from metformin, phenformin, buformin, or imeglimin, or a salt thereof, wherein the delayed-release formulation releases the biguanide compound downstream of duodenum to one or more regions of intestine.
Bioavailability capped versus immediate release
The delayed-release formulation has a bioavailability no more than 80% of the bioavailability of the biguanide compound in an immediate-release composition having the same amount of biguanide compound.
Resulting circulating plasma concentration below about 1 µg/mL
The resulting circulating plasma concentration of the biguanide compound is below about 1 µg/mL.
Treat metabolic disorder despite specified contraindicating conditions
The method treats a metabolic disorder comprising a hyperglycemic condition, a disorder of lipid metabolism, or both, in a patient having a contraindicating condition limited to nausea, vomiting, dyspepsia, dizziness, headache, or renal impairment.
The claim coverage centers on treating hyperglycemic and/or lipid metabolism disorders using an oral delayed-release biguanide formulation that releases downstream of the duodenum, has no more than 80% bioavailability relative to immediate release, and results in circulating plasma concentrations below about 1 µg/mL, for patients with specified contraindicating conditions.
Stated Advantages
Improved GI tolerability reported for delayed-release metformin versus immediate-release.
Reduced systemic metformin exposure reported for delayed-release metformin versus immediate-release.
Preserved meal-enhanced gut hormone responses (e.g., GLP-1 and PYY) reported with delayed-release metformin.
Glucose/insulin effects reported as preserved with delayed-release metformin.
Documented Applications
Treating a metabolic disorder in a patient having a condition that contraindicates treatment with a biguanide compound, including hyperglycemic conditions and/or disorders of lipid metabolism, where contraindication is due to gastrointestinal condition caused by biguanide administration (nausea, vomiting, or dyspepsia) and/or dizziness, headache, or renal impairment.
Comparing delayed-release versus immediate-release metformin with pharmacokinetic and pharmacodynamic assessment, including reduced systemic exposure with preserved meal-enhanced gut hormone responses and glucose/insulin effects.
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