Improvements in Glycemic Parameters Associated With Magnitude of Weight Loss (WL) in Overweight/Obese Subjects Receiving Phentermine and Topiramate Extended-Release (PHEN/TPM ER) Over 2 Years

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 660-676-Clinical Obesity Treatment
Clinical
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-663
Lawrence J Cheskin*1 and Charles H Bowden2
1Johns Hopkins Weight Management Center, Baltimore, MD, 2VIVUS, Inc., Mountain View, CA
In obese and overweight individuals, WL can significantly improve glycemic control, with benefits increasing with greater degrees of WL.  PHEN/TPM ER demonstrated significant WL and improvements in glycemia in obese/overweight (body mass index ≥27 and ≤45 kg/m2) adults with ≥2 weight-related comorbidities in the 56-week CONQUER study and its 52-week extension, SEQUEL. This post hoc analysis assessed long-term improvements in glycemia based on magnitude of WL, regardless of dose (<5%, n=258; ≥5 to <10%, n=155; ≥10% to <15%, n=116; and ≥15%, n=146) in the SEQUEL population (ITT-LOCF). This analysis included subjects with or without diabetes. Subjects maintained their randomization to lifestyle modifications plus placebo (PBO; n=227), PHEN 7.5mg/TPM ER 46mg (7.5/46; n=153), or PHEN 15mg/TPM ER 92mg (15/92; n=295) for a total of 108 weeks. At CONQUER baseline, fasting glucose (FG; mean 109.2mg/dL), fasting insulin (FI; mean 17.4μIU/mL), and HbA1c (mean 6.0%) levels were similar across all WL categories. At week 108, PHEN/TPM ER led to significant mean absolute WL vs PBO: -2.1kg, -9.6kg, and -10.9kg for PBO, 7.5/46, and 15/92, respectively (P<.0001 vs PBO, all comparisons). Significant improvements in glycemic parameters were seen in all WL categories ≥5% vs <5% at week 108: least-squares (LS) mean change for those achieving WL of <5%, ≥5% to <10%, ≥10% to <15%, and ≥15%, respectively, for HbA1c (%) were 0.2, -0.1, -0.2, and -0.3 (P<.0001 vs <5%, all comparisons); for FG (mg/dL) were 4.4, -4.0, -10.0, and -12.8 (P<.0001 vs <5%, all comparisons); and for FI (μIU/mL) were -1.1, -4.1, -7.6, and -9.0 (P≤.0007 vs <5%, all comparisons). Across treatment groups, regression analysis revealed that for every 5% WL, HbA1c declined by 0.1%, FG declined by 3.8mg/dL, and FI declined by 2.2μIU/mL (P<.0001 vs baseline, all comparisons). Similarly, for every 4.5kg WL, HbA1c decreased by 0.1%, FG by 3.2mg/dL, and FI by 2.0μIU/mL (P<.0001 vs baseline, all comparisons). The percentage of subjects with a net change in antidiabetic medications (medications added minus medications discontinued) was +7.3% for <5%, +2.6% for ≥5% to <10%, -0.9% for ≥10% to <15%, and, -2.0% for ≥15% WL. Common adverse events were dry mouth, paraesthesia, and constipation. The findings suggest that sustained WL may lead to long-term glycemic improvements in obese and overweight individuals, with glycemic benefits increasing with the magnitude of WL.

 Dr Cheskin is a stockholder and member of the National Advisory Board of VIVUS, Inc.

Disclosure: LJC: , Vivus USA, , Medifast, Inc., Medical Advisory Board Member, Vivus USA, Medical Advisory Board Member, Medifast, Inc. CHB: Employee, Vivus USA.

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Funding for editorial assistance was provided by VIVUS, Inc.