medwireNews: A weekly injection of tirzepatide results in a substantial bodyweight reduction over and above that achieved with lifestyle intervention in people with obesity, show the SURMOUNT-1 findings
Indeed, the investigators found that about a third of people on the highest two tirzepatide doses lost at least a quarter of their bodyweight during 72 weeks of treatment.
The results were presented at the 82nd ADA Scientific Sessions in New Orleans, Louisiana, and simultaneously published in The New England Journal of Medicine.
Louis Aronne discusses the results of SURMOUNT-1, and why he believes they may represent the start of a major shift in the treatment of people with obesity (8:47).
Addressing conference delegates, investigator Louis Aronne (Weill Cornell Medicine, New York, USA) said the results place the efficacy of tirzepatide for weight loss “between lap band and sleeve gastrectomy.”
And he stressed that the SURMOUNT-1 participants had considerably lower baseline BMIs than participants of surgery trials. He speculated that if tested in people with higher BMIs, who have more weight to lose, the 60% reduction in excess weight seen in SURMOUNT-1 could put tirzepatide “squarely in the range of bariatric surgical weight loss.”
All 2539 participants received regular lifestyle counseling over the course of the trial, promoting healthy, balanced meals with a 500 calorie/day deficit and at least 150 minutes of physical activity per week. Among those assigned to placebo, this resulted in an average weight loss of 3.1% over the 72 weeks of the trial.
But those taking tirzepatide achieved significantly larger weight reductions, of 15.0%, 19.5%, and 20.9% with the 5, 10, and 15 mg/week doses, respectively. The differences versus placebo ranged from 11.9 to 17.8 percentage points.
Between 85% and 91% of the tirzepatide-treated groups lost at least 5% of their baseline bodyweight, compared with 35% of the placebo group.
Moreover, 83.5%, 70.6%, and 56.7% of people taking the highest tirzepatide dose lost a respective 10%, 15%, and 20% or more of their starting bodyweight. The corresponding rates in the placebo group were 18.8%, 8.8%, and 3.1%.
And 32.3–36.2% of people on the highest tirzepatide doses lost at least a quarter of their bodyweight, compared with 1.5% of those in the placebo group.
These data were all for the treatment-regimen estimand; weight loss was a little higher for the efficacy estimand (ie, for participants who consistently took the medication as instructed), at an average weight loss of 22.5% with the highest tirzepatide dose, for example.
The majority (67.5%) of SURMOUNT-1 participants were women, and they were relatively young, with an average age of 44.9 years, but reported an average obesity duration of 14.4 years.
Their average BMI was 38.0 kg/m2; the researchers recruited people who had either a BMI of at least 30 kg/m2 or had a BMI of at least 27 kg/m2 plus one or more weight-related comorbidities, such as hypertension or obstructive sleep apnea.
At baseline, 40.6% of the trial population had prediabetes. By week 72, 95.3% of those taking tirzepatide had reverted to normoglycemia, compared with 61.9% of the placebo group. In addition, people taking tirzepatide had significantly greater improvements in blood pressure, lipid levels, liver enzymes, and fasting insulin level than those given placebo.
Participants in the tirzepatide group also reported significantly greater improvement in physical functioning on the SF-36 quality of life questionnaire than those in the placebo group.
As anticipated, gastrointestinal events were the most common adverse events in people taking tirzepatide, particularly nausea, which was reported by up to 33%. Diarrhea affected up to 23%, constipation up to 17%, and vomiting up to 12%. These events were mostly mild and transient, however, causing only approximately 2–3% of people to stop treatment.
Independent commentator Lee Caplan (The Obesity and Metabolism Institute, Boston, Massachusetts, USA) discussed the high complexity of bodyweight regulation and the difficulties in finding a single pharmacologic drug target that results in weight loss without risky side effects.
He stressed the importance of determining whether the superior efficacy of tirzepatide is due to its dual mechanism of action, or if it simply contains an exceptionally powerful glucagon-like peptide (GLP)-1 receptor agonist.
Caplan said that if other mechanisms besides GLP-1 signaling prove to have a powerful effect on fat mass regulation, “then we truly have the ability – as with hypertension, as with diabetes, as with other chronic diseases – to be able to hit it from multiple different mechanisms.”
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N Engl J Med 2022; doi:10.1056/NEJMoa2206038
ADA Scientific Sessions; New Orleans, Louisiana: 3–7 June 2022