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