Semaglutide + standard of care encourages weight loss in patients with T2D and high CV risk
The addition of the glucagon-like peptide-1 analogue semaglutide to standard of care resulted in sustained reduction in weight and waist circumference in individuals with type 2 diabetes (T2D) with high cardiovascular risk, according to the phase III SUSTAIN 6* trial presented at EASD 2017.
At 104 weeks, patients on semaglutide 0.5 mg experienced a significant reduction in body weight compared with those on placebo 0.5 mg (-3.6 vs -0.7 kg, estimated treatment difference [ETD], -2.87 kg) as did patients on semaglutide 1.0 mg compared with placebo 1.0 mg (-4.9 vs -0.5 kg, ETD, -4.35 kg; p<0.0001 for both comparisons). [EASD 2017, OP 01]
Thirty-six and 47 percent of patients on semaglutide 0.5 and 1.0 mg experienced weight loss of ≥5 percent of baseline body weight compared with 18 and 19 percent of their volume-matched placebo counterparts, while 13 and 21 percent of patients on semaglutide 0.5 and 1.0 mg experienced weight loss of ≥10 percent from baseline vs volume-matched placebos (6 and 7 percent, respectively; p<0.0001 for all comparisons).
There was also a significant reduction in waist circumference among patients on semaglutide 0.5 mg compared with placebo 0.5 mg (-2.7 vs -0.6 cm) and semaglutide 1.0 mg compared with placebo 1.0 mg (-4.2 vs -0.9 cm) corresponding to an ETD of -2.17 and -3.25, respectively (p<0.0001).
The results presented at EASD 2017 were that of a secondary outcome of the SUSTAIN 6 trial which was primarily a cardiovascular safety outcomes trial. Patients were 3,297 individuals aged ≥50 years with T2D and high cardiovascular risk (established cardiovascular disease, chronic heart failure [NYHA** class II or III]) or chronic kidney disease stage ≥3, or age ≥60 years with ≥1 cardiovascular risk factors who in addition to standard-of-care therapy, were randomized to receive once-weekly subcutaneous doses of semaglutide (0.5 or 1.0 mg) or corresponding placebo for 104 weeks (mean age 64.6 years, 60.7 percent male, mean [baseline] body weight 92.1 kg, duration of diabetes 13.9 years, HbA1c 8.7 percent). Lifestyle interventions were not included in the trial and 58 percent of participants were receiving insulin therapy.
According to Dr Agostino Consoli from the University of Chieti, Chieti, Italy, who presented the findings, weight loss was not dependent on baseline BMI.
“[T]he reduction vs placebo was consistently observed in all the baseline BMI categories [obese, less obese, normal weight, and lean subjects],” he said.
More patients on semaglutide experienced gastrointestinal (GI) adverse effects, namely nausea and vomiting, compared with those on placebo (21.9 percent vs 10.8 percent [0.5 mg] and 27.3 percent vs 10.6 percent [1.0 mg]), a finding which led the researchers to conduct a post hoc analysis to determine the impact of the GI events on weight loss.
The analysis showed that in patients on semaglutide 0.5 mg and 1.0 mg (vs placebo), the estimated indirect effect exerted by GI adverse events were -0.12 and -0.04 kg, respectively.
“Conversely, the vast majority of the weight loss, 2.75 kg in [the semaglutide] 0.5 mg arm and 4.32 kg in the [semaglutide] 1.0 mg arm could be ascribed directly to the effect of treatment,” said Consoli. “[T]he observed weight loss effect was independent of the occurrence of these GI adverse effects,” he said.