Combination treatment with phentermine-topiramate extended release (ER) and a digitally enhanced lifestyle intervention (DELI) results in a significant and sustained weight reduction, as well as a decrease in cardiovascular disease (CVD) risk, in adults with obesity, reports a study.
“In adults with obesity, adding phentermine-topiramate-ER to a DELI led to significantly greater weight loss and a decrease in estimated CVD risk compared with DELI and placebo,” the researchers said.
A 12-month, randomized, double-blind, placebo-controlled trial was conducted at a single tertiary academic centre in the UC from June 2020 to June 2022.
Eighty adults with obesity (BMI ≥30 kg/m2) participated in the DELI program, which consisted of in-person and telehealth modalities, dietary and physical activity goals, and use of a smartphone application integrated with digital devices (ie, Apple Watch and Bluetooth-enabled weight scale and blood pressure monitor).
The research team randomized participants 1:1 to receive either phentermine-topiramate-ER (n=42) or placebo (n=38) in addition to the DELI.
Participants who received phentermine-topiramate-ER lost a mean of 10.82 kg at 3 months compared with 4.04 kg among those who received placebo (mean difference ‒6.78 kg; p=0.002). At 12 months, weight loss was 15.32 kg with phentermine-topiramate-ER vs 5.85 kg with placebo (mean difference ‒9.48 kg; p<0.001). [Obesity 2026;34:524-536]
In addition, participants in the phentermine-topiramate-ER group showed a 3.35-percent decrease in the estimated atherosclerotic CVD risk relative to baseline (p=0.004).
Antiobesity agents
The weight loss seen in this study was much greater than that reported in previous studies with phentermine-topiramate-ER and close to the outcomes of newer antiobesity medications (AOMs), such as semaglutide. [Lancet 2011377:1341-1352; Obesity 2012;20,:330-342; N Engl J Med 2021;384:989-1002; JAMA Network Open 2022;5:e2231982]
In the CONQUER trial, participants lost 8.1 kg with phentermine-topiramate-ER 7.5/46 mg at 56 weeks relative to 1.4 kg with placebo.
“This substantial difference in weight loss could be attributed to the hybrid visit modality (remote and in-person) and the incorporation of digital devices to provide actionable feedback based on patients' data, which can lead to better adherence, as suggested by other studies,” the researchers said. [Diabetes 2024;26:2521-2523; Behav Sci 2024;14:480]
Previous trials have also demonstrated greater weight loss outcomes with AOMs combined with intense lifestyle interventions, but these involved nearly 30 visits during their study length, compared with only 15 hybrid visits in the current study. [Obesity 2011;19:110-120; Obesity 2019;27:75-86]
“Interestingly, in this study, as well as in previous trials of AOMs plus intense lifestyle interventions, participants assigned to placebo also achieved greater weight loss than in trials with less-intense lifestyle interventions,” the researchers said.
“This difference suggests that the weight loss achieved with AOMs could be enhanced by implementing a DELI program that can be adapted to different healthcare settings and patient-specific needs,” they added. [NEJM Evidence 2022;1:EVIDoa2200014]
“Further studies are warranted to determine whether a DELI provides an additive or synergistic benefit when combined with pharmacologic weight loss therapies and to evaluate the impact on physical activity, caloric intake, adverse events, and treatment adherence,” the researchers said.