Methods of preventing progression to type 2 diabetes mellitus
Inventors
Day, Wesley • TROUPIN, Barbara
Assignees
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Publication Number
US-10058532-B2
Publication Date
2018-08-28
Expiration Date
Abstract
The present invention provides compositions and methods for delaying or preventing progression to type 2 diabetes mellitus in individuals with prediabetes and metabolic syndrome.
Core Innovation
The described invention provides a method of delaying the progression from prediabetes to diabetes in a patient. The method includes identifying a patient at risk for developing type 2 diabetes by determining that the patient has at least one specified glycemic condition, including HbA1c levels between 5.7% and 6.4%, plasma glucose levels between 7.8 mmol/L and 11 mmol/L, and blood glucose levels between 6.1 mmol/L and 7.0 mmol/L.
After identifying a patient at risk, the method administers an oral dosage form comprising immediate release phentermine and controlled release topiramate. The oral dosage form is characterized as immediate release phentermine together with controlled release topiramate, including dose combinations associated with PHEN/TPM ER regimen strengths. The regimen is presented as a way to address prediabetes and delay progression to diabetes.
The disclosed approach is further supported by described outcomes from a SEQUEL subgroup, including reduced annualized incidence of type 2 diabetes compared with placebo and correlations with the magnitude of weight loss. The document also reports improvements in glycemic and insulin sensitivity and cardiometabolic markers, reductions in inflammation markers, increased adiponectin, and mention of MetS remission and tolerability over 108 weeks with lifestyle counseling.
Claims Coverage
The partial content includes one independent claim that covers at-risk patient identification using specified glycemic thresholds and administration of an oral dosage form containing immediate release phentermine and controlled release topiramate. Dependent claims further specify formulation dose strengths and refine patient selection using MetS criteria and biomarker and marker outcome targets.
At-risk patient identification for prediabetes progression delay
Identifying a patient at risk for developing type 2 by determining the patient has at least one of the following: HbA1c levels between 5.7% and 6.4%, plasma glucose levels between 7.8 mmol/L and 11 mmol/L, or blood glucose levels between 6.1 mmol/L and 7.0 mmol/L.
Oral dosage form with immediate release phentermine and controlled release topiramate
Administering to the patient an oral dosage form comprising immediate release phentermine and controlled release topiramate.
Specific immediate-release phentermine and controlled-release topiramate dose combinations
The oral dosage form comprises specified dose combinations of immediate-release phentermine with controlled-release topiramate, including dose strengths described as 3.75 mg/23 mg, 7.5 mg/46 mg, 11.25 mg/69 mg, and 15 mg/92 mg.
Sequential oral dosage forms with distinct durations and dose strengths
Administering two sequential oral dosage forms: a first oral dosage form containing 3.75 mg immediate-release phentermine with 23 mg controlled-release topiramate for 1 to 2 weeks, and a second oral dosage form containing 7.5 mg immediate-release phentermine with 46 mg controlled-release topiramate for 3 months.
Metabolic syndrome identification using multi-criteria thresholds
Identifying a patient with MetS by determining the patient meets at least three specified clinical criteria for waist circumference, triglycerides, HDL cholesterol, blood pressure, and fasting blood glucose, including threshold- or medication-based definitions.
Inflammation and adipokine biomarker targets after administration
Achieving one or more specified biomarker changes after administering the oral dosage form, including lowering hs-CRP to below 3.0 mg/L, lowering fibrinogen to at least 400 mg/dL, and increasing adiponectin to a level higher than the patient’s pre-administration level.
Improved metabolic marker outcomes
Improving in a patient at least one selected metabolic marker including fasting glucose, fasting insulin, 2-hour post-OGTT glucose, fasting triglycerides, or HDL-C levels.
Across the independent claim and its dependents, coverage centers on identifying at-risk prediabetes patients using specified glycemic thresholds and administering an oral PHEN/TPM ER dosage form comprising immediate release phentermine and controlled release topiramate. Dependent claims further narrow formulation dose strengths, add sequential dosing concepts, refine selection using MetS multi-criteria thresholds, and specify biomarker and metabolic marker improvements.
Stated Advantages
Delays progression from prediabetes to diabetes.
Reduced annualized incidence of type 2 diabetes compared with placebo.
Greater weight loss versus placebo in the SEQUEL subgroup.
Improves glycemic and insulin sensitivity and cardiometabolic markers.
Reduces inflammation markers including hs-CRP and fibrinogen.
Increases adiponectin.
Reports MetS remission.
Tolerability over 108 weeks with lifestyle counseling.
Documented Applications
Using an oral immediate-release phentermine plus controlled-release topiramate regimen to delay progression from prediabetes to diabetes in patients identified as at risk for developing type 2.
Application of the SEQUEL subgroup outcomes for assessing effects including annualized incidence of type 2 diabetes, weight loss, glycemic and insulin sensitivity, cardiometabolic markers, inflammation markers, adiponectin, and MetS remission.
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