# Addition of Phentermine‐Topiramate to a Digitally Enhanced Lifestyle Intervention: A Double‐Blind Randomized Clinical Trial

## TL;DR

Adding phentermine-topiramate to a digital lifestyle program significantly improved weight loss and reduced heart disease risk in people with obesity.

## Contribution

This study shows that combining phentermine-topiramate with a digitally enhanced lifestyle intervention leads to greater weight loss and cardiovascular benefits than either approach alone.

## Key findings

- Participants taking phentermine-topiramate lost significantly more weight than those on placebo at 3 and 12 months.
- The drug combination reduced estimated atherosclerotic cardiovascular disease risk by 3.35% compared to baseline.
- Weight loss with the digital program plus phentermine-topiramate exceeded results from prior trials without the digital intervention.

## Abstract

This study compared the effects of phentermine‐topiramate‐ER (mid‐dose 7.5/46 mg) versus placebo on weight loss and cardiovascular disease (CVD) risk outcomes when used as an adjunct to a digitally enhanced lifestyle intervention (DELI).

We conducted a 12‐month, randomized, double‐blind, placebo‐controlled trial at a single tertiary academic center in the United States (June 2020–June 2022). Eighty participants with obesity (BMI ≥ 30 kg/m2) were enrolled in the DELI program, consisting of in‐person and telehealth modalities, dietary and physical activity goals, and use of a smartphone application integrated with digital devices (Apple Watch and Bluetooth‐enabled weight scale and blood pressure monitor). Participants were randomized 1:1 to receive either phentermine‐topiramate‐ER (n = 42) or placebo (n = 38) in addition to the DELI.

At 3 months, the phentermine‐topiramate group lost a mean of 10.82 kg versus 4.04 kg in the placebo group (mean difference −6.78 kg; p = 0.002). At 12 months, weight loss was 15.32 kg versus 5.85 kg, respectively (mean difference −9.48 kg; p < 0.001). Participants receiving phentermine‐topiramate‐ER experienced a 3.35% reduction in the estimated atherosclerotic CVD risk compared to baseline (p = 0.004).

Phentermine‐topiramate‐ER, when combined with a DELI, produced significant and sustained weight loss and reduced CVD risk in adults with obesity.

ClinicalTrials.gov: NCT04408586

What is already known?○The use of digital strategies—such as telehealth visits, activity trackers, and mobile applications—in weight loss interventions has increased in recent years.○Prior studies have shown modest and heterogeneous effects of these strategies on weight loss outcomes, and few have evaluated their combination with pharmacotherapy.
What does this study add?○In adults with obesity, adding once‐daily phentermine–topiramate‐ER (mid‐dose 7.5/46 mg) to a digitally enhanced lifestyle intervention (DELI) produced significantly greater weight loss compared with placebo at 3, 6, 9, and 12 months and reduced estimated atherosclerotic cardiovascular disease risk at 12 months.○The weight loss achieved with a DELI plus phentermine–topiramate‐ER exceeded that reported in prior phentermine–topiramate trials without DELI.
How might these results change the direction of research or the focus of clinical practice?○Incorporating a DELI into obesity management could amplify the effects of both pharmacologic and lifestyle‐only approaches while improving cardiometabolic outcomes.○Future studies should directly compare a DELI with traditional lifestyle programs, evaluate its combination with other obesity medications, and assess cost‐effectiveness and scalability across health care settings.

What is already known?○The use of digital strategies—such as telehealth visits, activity trackers, and mobile applications—in weight loss interventions has increased in recent years.○Prior studies have shown modest and heterogeneous effects of these strategies on weight loss outcomes, and few have evaluated their combination with pharmacotherapy.

The use of digital strategies—such as telehealth visits, activity trackers, and mobile applications—in weight loss interventions has increased in recent years.

Prior studies have shown modest and heterogeneous effects of these strategies on weight loss outcomes, and few have evaluated their combination with pharmacotherapy.

What does this study add?○In adults with obesity, adding once‐daily phentermine–topiramate‐ER (mid‐dose 7.5/46 mg) to a digitally enhanced lifestyle intervention (DELI) produced significantly greater weight loss compared with placebo at 3, 6, 9, and 12 months and reduced estimated atherosclerotic cardiovascular disease risk at 12 months.○The weight loss achieved with a DELI plus phentermine–topiramate‐ER exceeded that reported in prior phentermine–topiramate trials without DELI.

In adults with obesity, adding once‐daily phentermine–topiramate‐ER (mid‐dose 7.5/46 mg) to a digitally enhanced lifestyle intervention (DELI) produced significantly greater weight loss compared with placebo at 3, 6, 9, and 12 months and reduced estimated atherosclerotic cardiovascular disease risk at 12 months.

The weight loss achieved with a DELI plus phentermine–topiramate‐ER exceeded that reported in prior phentermine–topiramate trials without DELI.

How might these results change the direction of research or the focus of clinical practice?○Incorporating a DELI into obesity management could amplify the effects of both pharmacologic and lifestyle‐only approaches while improving cardiometabolic outcomes.○Future studies should directly compare a DELI with traditional lifestyle programs, evaluate its combination with other obesity medications, and assess cost‐effectiveness and scalability across health care settings.

Incorporating a DELI into obesity management could amplify the effects of both pharmacologic and lifestyle‐only approaches while improving cardiometabolic outcomes.

Future studies should directly compare a DELI with traditional lifestyle programs, evaluate its combination with other obesity medications, and assess cost‐effectiveness and scalability across health care settings.