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Tirzepatide shows success in maintaining weight reduction in obese adults

A recent study published within the Journal of the American Medical Association evaluated the consequences 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 reduction achieved through caloric restriction is difficult. Thus, adjunctive anti-obesity medications are beneficial to advertise weight reduction, facilitate weight maintenance, and improve outcomes.

Evidence suggests that anti-obesity medications, equivalent to orlistat, naltrexone/bupropion, glucagon-like peptide 1 (GLP-1) receptor agonists, and phentermine/topiramate, may help maintain weight reduction. 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

In regards to the study

In the current study, researchers investigated the consequences of continued treatment with tirzepatide on maintaining weight reduction in chubby or obese individuals. This trial, SURMOUNT-4, was a randomized withdrawal study conducted in the US, 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 the very least one weight-related complication (heart problems, sleep apnea, hypertension, or dyslipidemia).

Individuals with diabetes or planned/prior surgery for obesity and people on weight reduction medications inside the past three months were excluded. Tirzepatide was administered as a subcutaneous injection once every week. Through the lead-in period, the tirzepatide dose was incremented by 2.5 mg every 4 weeks until the utmost tolerated dose (10 or 15 mg) was achieved.

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


Overall, 783 participants were enrolled within the lead-in period. Of those, 113 individuals were excluded from randomization resulting from hostile events, withdrawal, and protocol deviation, amongst other reasons. In total, 670 participants were randomized to proceed treatment with the utmost tolerated dose of tirzepatide or receive a placebo.

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

Through the 36-week lead-in period, the typical weight reduction was 20.9% amongst randomized participants. Moreover, BMI and waist circumference decreased, whereas patient-reported outcomes, lipid levels, glycemic parameters, and blood pressure improved. The common 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 the very least 80% of the load loss achieved throughout the lead-in period. Besides, continuing tirzepatide treatment beyond the lead-in period decreased the danger of returning to > 95% baseline weight by 98% for individuals who lost ≥ 5% body weight since week 0.

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

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

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


The findings emphasize continuing therapy to sustain weight reduction and stop weight regain in chubby and obese adults. Although placebo recipients ended the study with a considerable decrease in body weight, improvements in cardiometabolic parameters were reversed. In sum, after attaining weight reduction throughout the 36-week lead-in period, adults who continued the treatment with the utmost tolerated dose of tirzepatide for one yr showed superior weight maintenance in comparison with placebo recipients.

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