Tirzepatide shows success in maintaining weight loss in obese adults

A recent study published in the Journal of the American Medical Association evaluated the effects of tirzepatide on maintaining weight reduction in obese adults.

Obesity is a severe, progressive, chronic, and relapsing disease, and lifestyle interventions are the cornerstone to managing it. Nonetheless, sustaining weight loss achieved through caloric restriction is challenging. Thus, adjunctive anti-obesity medications are recommended to promote weight loss, facilitate weight maintenance, and improve outcomes.

Evidence suggests that anti-obesity medications, such as orlistat, naltrexone/bupropion, glucagon-like peptide 1 (GLP-1) receptor agonists, and phentermine/topiramate, may help maintain weight loss. Tirzepatide combines GLP-1 and glucose-dependent insulinotropic polypeptide agonism, producing synergistic effects on food intake, appetite, and metabolic function.

Study: Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity. Image Credit: kurhan / Shutterstock

About the study

In the present study, researchers investigated the effects of continued treatment with tirzepatide on maintaining weight loss in overweight or obese individuals. This trial, SURMOUNT-4, was a randomized withdrawal study conducted in the United States, Argentina, Taiwan, and Brazil between March 29, 2021, and May 18, 2023.

The trial included a 36-week open-label lead-in tirzepatide treatment period, followed by a 52-week placebo-controlled double-blind period. Eligible participants were adults aged 18 or older with a body mass index (BMI) ≥ 30 kg/m2 or 27 kg/m2 and at least one weight-related complication (cardiovascular disease, sleep apnea, hypertension, or dyslipidemia).

Individuals with diabetes or planned/prior surgery for obesity and those on weight loss medications within the past three months were excluded. Tirzepatide was administered as a subcutaneous injection once a week. During the lead-in period, the tirzepatide dose was incremented by 2.5 mg every four weeks until the maximum tolerated dose (10 or 15 mg) was achieved.

At the end of 36 weeks, participants were randomized to continue treatment with the maximum tolerated dose of tirzepatide or switch to a placebo for 52 weeks. The primary endpoint was the percent change in body weight between weeks 36 and 88. Secondary endpoints were weight maintenance, regain, and changes in cardiometabolic risk factors.

Findings

Overall, 783 participants were enrolled in the lead-in period. Of these, 113 individuals were excluded from randomization due to adverse events, withdrawal, and protocol deviation, among other reasons. In total, 670 participants were randomized to continue treatment with the maximum tolerated dose of tirzepatide or receive a placebo.

Most randomized individuals were female and White. The average duration of obesity was 15.5 years. Nearly 70% of participants had at least one weight-related complication. Dyslipidemia and hypertension were the most prevalent weight-related complications. Clinical characteristics and demographics were similar between groups.

During the 36-week lead-in period, the average weight loss was 20.9% among randomized participants. Furthermore, BMI and waist circumference decreased, whereas patient-reported outcomes, lipid levels, glycemic parameters, and blood pressure improved. The average percent change in weight from weeks 36 to 88 was -5.5% with tirzepatide and 14% with placebo.

At week 88, a significantly higher percentage of tirzepatide recipients maintained at least 80% of the weight loss achieved during the lead-in period. Besides, continuing tirzepatide treatment beyond the lead-in period decreased the risk of returning to > 95% baseline weight by 98% for those who lost ≥ 5% body weight since week 0.

Continued treatment was associated with significant improvements in BMI, glycated hemoglobin, fasting glucose, blood pressure, insulin, and lipid levels by week 88. Tirzepatide treatment was associated with improvements in BMI, patient-reported outcomes, and cardiometabolic parameters throughout the study (from week 0).

Overall, 81% of participants had at least one treatment-emergent adverse event during the lead-in period. Nausea, diarrhea, constipation, and vomiting were the most common adverse events. In the double-blind period, 60.3% of tirzepatide recipients and 55.8% of placebo recipients reported at least one adverse event.

Gastrointestinal disorders and coronavirus disease 2019 (COVID-19) were the most common in the double-blind period. Sixteen participants in the lead-in period and ten during the double-blind period experienced serious adverse events. One death occurred during the lead-in period and two in the double-blind period. The investigators deemed these deaths unrelated to the study drug.

Conclusions

The findings emphasize continuing therapy to sustain weight reduction and prevent weight regain in overweight and obese adults. Although placebo recipients ended the study with a substantial decrease in body weight, improvements in cardiometabolic parameters were reversed. In sum, after attaining weight reduction during the 36-week lead-in period, adults who continued the treatment with the maximum tolerated dose of tirzepatide for one year showed superior weight maintenance compared to placebo recipients.

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