Prevention of type 2 diabetes in subjects with prediabetes and metabolic syndrome treated with phentermine and topiramate extended release


Garvey WT, Ryan DH, Henry R, et al. Prevention of type 2 diabetes in subjects with prediabetes and metabolic syndrome treated with phentermine and topiramate extended release. Diabetes Care. 2014;37:912-921. 


This subanalysis of the SEQUEL study demonstrated a greater than 70% reduction in type 2 diabetes incidence among patients treated with phentermine (PHEN) and topiramate (TPM) extended release (ER) compared with those who received placebo.

  

Commentary Thumb Fonseca T2D Prevention 

Primary endpoint
Percent weight loss from baseline at Week 108, the study’s primary endpoint, was as follows (least-squares mean):

  • PHEN 7.5 mg plus TPM 46 mg qd plus lifestyle modifications (n=115): -10.9% (P<0.0001 vs placebo)
  • PHEN 15 mg plus TPM 92 mg qd plus lifestyle modifications (n=201): -12.1% (P<0.0001 vs placebo)
  • Placebo qd plus lifestyle modifications (n=159) : -2.5%

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SEQUEL Subanalysis Percent Weight Loss from Baseline at Wk 108 Primary Endpoint   
SEQUEL Subanalysis: Percent Weight Loss
From Baseline at Wk 108 Primary Endpoint
 

Type 2 diabetes incidence
The annualized incidence of type 2 diabetes at Week 108, a prespecified secondary endpoint, was as follows:

  • PHEN 7.5 mg plus TPM 46 mg qd plus lifestyle modifications (n=115): 1.8, a 70.5% reduction vs placebo (P<0.05)
  • PHEN 15 mg plus TPM 92 mg qd plus lifestyle modifications (n=201): 1.3, a 78.7% reduction vs placebo (P<0.05)
  • Placebo qd plus lifestyle modifications (n=159): 6.1

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SEQUEL Subanalysis Annualized Incidence of Type 2 Diabetes at Wk 108   
SEQUEL Subanalysis: Annualized Incidence of
Type 2 Diabetes at Wk 108
 

Among subjects with prediabetes and metabolic syndrome, respectively, annualized reduction in type 2 diabetes incidence rates were as follows:

  • Prediabetes
    • PHEN 7.5 mg plus TPM 46 mg qd plus lifestyle modifications (n=83): 1.8, a 48.6% reduction vs placebo
    • PHEN 15 mg plus TPM 92 mg qd plus lifestyle modifications (n=129): 0.4, an 88.6% reduction vs placebo (P=0.0125 vs placebo)
    • Placebo qd plus lifestyle modifications (n=103): 3.5
     
  • Metabolic syndrome
    • PHEN 7.5 mg plus TPM 46 mg qd plus lifestyle modifications (n=105): 1.5, a 76.6% reduction vs placebo (P=0.0093 vs placebo)
    • PHEN 15 mg plus TPM 92 mg qd plus lifestyle modifications (n=190): 1.3, a 79.7% reduction vs placebo (P=0.0007 vs placebo)
    • Placebo qd plus lifestyle modifications (n=151): 6.4  
     

Greater weight loss was associated with greater reduction in incidence of type 2 diabetes, regardless of treatment group. Weight loss at 108 weeks and annualized type 2 diabetes incidence rates (P<0.05 vs <5% weight loss for all comparisons):

  • <5%: 6.3
  • ≥5% to >10%: 1.3
  • ≥10% to >15%: 1.3
  • ≥15%: 0.9

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SEQUEL Subanalysis Reduction of Type 2 Diabetes Incidence Related to Greater Weight Loss   
SEQUEL Subanalysis: Reduction of Type 2 Diabetes
Incidence Related to Greater Weight Loss
 

Cardiometabolic risk factors and additional parameters
Improvements in cardiometabolic risk factors, specifically triglycerides, HDL-C, fasting glucose, fasting insulin, and 2-h post-OGTT glucose, were also seen in PHEN/TPM ER-treated subjects vs those who received placebo. No significant differences in blood pressure were seen with PHEN/TPM ER vs placebo. A significantly greater percentage of subjects who received PHEN/TPM ER had metabolic syndrome remission vs placebo (P=0.0001).

PHEN/TPM ER was well tolerated; more subjects in the treatment groups experienced paresthesia, sinusitis, dry mouth, constipation, headache, and dysgeusia compared with subjects who received placebo. 

About this study
This subanalysis of the SEQUEL study examined reduction in progression of type 2 diabetes and/or cardiometabolic disease in a cohort of subjects with prediabetes or metabolic syndrome treated with PHEN/TPM ER plus lifestyle modifications. SEQUEL was a 52-week extension of CONQUER; CONQUER was 56-week, randomized, double-blind study examining PHEN/TPM ER plus lifestyle modifications for weight loss in overweight/obese adults (BMI 27-45 kg/m2) with ≥2 weight-related comorbidities.* Subjects received PHEN 7.5 mg plus TPM 46 mg qd plus lifestyle modifications (n=115), PHEN 15 mg plus TPM 92 mg qd plus lifestyle modifications (n=201), or placebo qd plus lifestyle modifications (n=159). The primary endpoint was percent weight loss from baseline at 108 weeks.

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SEQUEL Subanalysis Design   
SEQUEL Subanalysis: Design

*Central adiposity, dyslipidemia, hypertension, or type 2 diabetes

PHEN/TPM ER is not approved to prevent and/or reduce the progression of type 2 diabetes or cardiometabolic disease by the U.S. Food and Drug Administration.

ER=extended release; PHEN=phentermine; TPM=topiramate

 
 
 
  

Any pharmacologic agents discussed are approved for use in the United States by the U.S. Food and Drug Administration (FDA) unless otherwise noted. Consult individual prescribing information for approved uses outside of the United States. 

May 2014 

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

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Last Modified: 8/4/2014