medwireNews: SURMOUNT-2 trial results show bodyweight reductions with tirzepatide that rival those seen with other approved anti-obesity medications in people with type 2 diabetes, say the investigators.
Treatment with tirzepatide for 72 weeks in patients with a mean baseline body weight of 100.7 kg and an average BMI of 36.1 kg/m2 resulted in an average body weight reduction of 12.8 percentage points (12.9 kg) with a 10 mg dose and 14.7 percentage points (14.8 kg) with 15 mg, compared with 3.2 percentage points (3.2 kg) with placebo.
This meant tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, was superior to placebo with significant treatment differences of 9.6 percentage points and 11.6 percentage points with the 10 and 15 mg doses, respectively, Timothy Garvey (University of Alabama at Birmingham, USA) and colleagues report in The Lancet.
They note that 79–83% of patients achieved a weight reduction of at least 5% with tirzepatide 10 or 15 mg compared with 32% with placebo, and at the higher 15 mg dose the rates for weight reductions of 10% or higher, 15% or higher, and 20% or higher at week 72 were a respective 64.8%, 48.0%, and 30.8%, versus corresponding rates with placebo of 9.5%, 2.7% and 1.0%
“[T]reatment with tirzepatide in SURMOUNT-2 resulted in a magnitude of mean weight reduction that has previously only been observed in people without type 2 diabetes on the most effective of medications,” say the researchers.
“In fact, it has been proposed that agents that produce mean weight reduction of about 15% in people with obesity represent a newer generation of anti-obesity medications because this degree of weight loss is sufficient to treat or prevent a wider array of obesity-related complications.”
The study, which was simultaneously presented at the 83rd ADA Scientific Sessions in San Diego, California, USA, included 938 people with type 2 diabetes (51% women, 76% White, 60% Hispanic or Latino) aged an average of 54 years.
Tirzepatide was also beneficial in terms of glycemic control. Among the 623 individuals taking the drug, glycated hemoglobin (HbA1c) levels fell by a significant 2.1 percentage points, from an average of 8.0% (64.0 mmol/mol) at baseline to 5.9–6.0% (41.0–42.1 mmol/mol) at week 72. This was significantly greater than the average 0.5 percentage-point reduction achieved with placebo, from a mean of 7.9% (62.8 mmol/mol) to 7.5% (58.5 mmol/mol).
Garvey and team highlight that around half (50.2–55.3%) of patients treated with tirzepatide achieved normoglycemia at an HbA1c level below 5.7%, compared with 2.8% of those given placebo.
The HbA1c targets were reached without any cases of severe hypoglycemia and level 2 hypoglycemia (<54 mg/dL [3.0 mmol/L]) rates were low, reported by 4–5% of patients in the tirzepatide group compared with 1% of those in the placebo group.
Further benefits with tirzepatide included significant improvements in health-related quality of life, including physical function, as well as cardiometabolic risk factors such as waist circumference, systolic and diastolic blood pressure, fasting triglycerides, and high-density lipoprotein (HDL), and non-HDL cholesterol.
“These improvements in cardiometabolic risk factors, coupled with the magnitude of weight reduction, have the potential to translate over time to reduced cardiovascular disease, chronic kidney disease, and non-alcoholic fatty liver disease, among other outcomes,” write Garvey et al.
The treatment groups did not significantly differ in terms of treatment-emergent adverse events, which occurred in 71–78% of tirzepatide-treated patients and 76% of placebo-treated individuals.
The most common of these in the tirzepatide arm were gastrointestinal disorders, including diarrhea, nausea, and vomiting. They tended to occur mainly during dose escalation and were mostly mild to moderate in severity, with only 4–7% leading to discontinuation.
Serious adverse events were seen in 6–9% of patients given tirzepatide, compared with 7% of placebo-treated patients and there were two deaths, both in the tirzepatide 10 mg group, neither of which were considered related to the drug.
The researchers conclude: “Both doses of tirzepatide provided substantial and clinically meaningful bodyweight reductions.”
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Lancet 2023; doi:10.1016/S0140-6736(23)01200-X
ADA Scientific Sessions; San Diego, California: 23–26 June 2023