Weight-loss therapy in type 2 diabetes effects of phentermine and topiramate extended-release


Garvey WT, Ryan DH, Bohannan NJV, et al. Weight-loss therapy in type 2 diabetes: effects of phentermine and topiramate extended-release. Diabetes Care. 2014;37(12):3309-3316.


DM-230 was a 28-week, double-blind continuation of a 28-week, phase 2, randomized, double-blind, placebo-controlled study (OB-202) assessing the efficacy and safety of combination phentermine (PHEN) and topiramate (TPM) for management of hyperglycemia among obese subjects with type 2 diabetes. This report also addresses previously unpublished data from the predefined subset of CONQUER subjects with type 2 diabetes at entry. CONQUER was a 56-week, double-blind, placebo-controlled study assessing the efficacy and safety of PHEN and TPM extended release in obese and overweight adults with two or more weight-related comorbidities. Baseline characteristics were similar across treatment arms in both studies; subjects in CONQUER had shorter duration and less severe diabetes compared with those in OB-202/DM-230.
  

Commentary Thumb Inzucchi Phentermine Plus 


Results:
 

  • At week 56 in the OB-202/DM-230 study, change in weight (ITT-LOCF) was -2.7% for placebo and -9.4% for PHEN/TPM ER 15/92 (P<0.0001 vs placebo).
  • At week 56, 65% of PHEN/TPM ER subjects had achieved ≥5% weight loss vs 24% of the placebo group (ITT-LOCF; P<0.0001).
  • A total of 37% of PHEN/TPM ER subjects had achieved ≥10% weight loss vs 9% of placebo subjects (ITT-LOCF; P=0.0004) (not shown).


In the OB-202/DM-230 study, subjects assigned to receive PHEN/TPM ER had a greater least-squares mean decrease in A1C of -1.6% vs -1.2% in the placebo group (ITT-LOCF; P<0.05). A significantly greater percentage of PHEN/TPM ER patients achieved the A1C goal of ≤7.0% compared with placebo patients (53% vs.40%; ITT-LOCF; P<0.05). A significantly greater percentage of PHEN/TPM ER patients achieved the A1c target of ≤6.5% compared with placebo patients (32% vs 16%; ITT-LOCF; P<0.05).
  
In CONQUER, differences in the achievement of A1C targets at week 56 were not significant within a subgroup of subjects with type 2 diabetes and A1C levels of >7.0% at baseline.

In both studies, treatment with PHEN/TPM ER and lifestyle modifications led to reductions in systolic blood pressure (SBP), diastolic blood pressure, and triglycerides, and increases in HDL-C. In the OB-202/DM-230 study, treatment with PHEN/TPM ER resulted in a -7.2 mm Hg LS mean reduction in SBP at week 56, which was significantly greater than the -2.4 mm Hg decrease observed with placebo (P<0.05; ITT-LOCF).
  
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In OB-202/DM-202, a greater percentage of PHEN/TPM ER-treated subjects decreased the number of antidiabetic medications taken during the study period compared with the placebo group: 18.7% vs 5.5%, respectively. Also, fewer PHEN/TPM ER-treated subjects required an increase in antidiabetic medications: 21.3% vs 29.1%
  
In CONQUER, there were greater reductions in antidiabetic medications, as well as less need to augment diabetes therapy, in the PHEN/TPM ER groups compared with the placebo group.
 


In OB-202/DM-230, the most commonly reported treatment-emergent adverse events (AEs) in the PHEN/TPM ER group that occurred more often than in the placebo group over 56 weeks were paraesthesia, constipation, and nausea. The majority of AEs were mild (placebo group 69.1%, PHEN/TPMER group 60.0%). Discontinuation of study drug due to AEs was rare, occurring in one subject from the PHEN/TPM ER group.

In CONQUER, the majority of AEs were mild to moderate in severity. Fifteen subjects (5 receiving placebo, 4 receiving PHEN/TPM ER 7.5/46, 6 receiving PHEN/TPM ER 15/ 92) reported 24 SAEs through 56 weeks. Two serious AEs (chest pain and nephrolithiasis) (PHEN/TPM ER 15/92 group) were classified as treatment related. Study drug was withdrawn, and both events were resolved. Discontinuation rates due to treatment-emergent AEs were 5.7%, 3.0%, and 12.8% for the placebo, PHEN/TPM ER 7.5/46, and PHEN/ TPM ER 15/92 groups, respectively.


Treatment with lifestyle interventions plus PHEN/TPM ER resulted in weight loss among obese/overweight subjects with type 2 diabetes, which was sustained for 1 year. Nearly two-thirds of subjects achieved ≥5% weight loss in the OB-202/DM-203. PHEN/TPM ER-assisted weight loss was accompanied by improvements in glycemic control, along with less need for conventional glucose-lowering medications.

All slides available for download in the Slide Library.

The combination of phentermine and topiramate is not FDA approved for the treatment of hyperglycemia, dyslipidemia, or hypertension in the United States.

ITT=intention to treat; LOCF=last observation carried forward; PHEN=phentermine; TPM ER=topiramate extended release

Related content: 

Silvio E. Inzucchi, MD, on Phentermine Plus Topiramate for Weight Loss in Type 2 Diabetes 

Obesity Week 2014 full coverage 

Vivian A. Fonseca, MD, on Type 2 Diabetes Prevention in SEQUEL 

SEQUEL: Longer-Term Safety, Efficacy of Phentermine + Topiramate for Weight Reduction Among Overweight or Obese Individuals with Cardiometabolic Disease 

CONQUER: Safety, Efficacy of Phentermine + Topiramate for Weight Reduction Among Overweight or Obese Individuals with Weight-Related Comorbidities 

EQUATE: Phentermine/Topiramate Combination Is Greater Than the Sum of Its Parts 

  

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. 

November 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: 12/10/2014