Semaglutide helps lower HbA1c, body weight of T2D patients

Treatment with semaglutide leads to clinically significant decreases in haemoglobin A1C (HbA1c) and body weight in patients with type 2 diabetes (T2D) across the SUSTAIN 1–7 trials, regardless of race and ethnicity, results of a posthoc analysis have shown.

Efficacy and safety of semaglutide were compared in race and ethnicity subgroups across the SUSTAIN trials via a posthoc analysis of data obtained from phase III randomized SUSTAIN 1–5 and 7 (pooled) and SUSTAIN 6 trials.

A total of 3,074 patients from SUSTAIN 1–5 and 7 and 1,648 from SUSTAIN 6 were included. Participants received semaglutide 0.5 or 1.0 mg, placebo, or active comparator (sitagliptin 100 mg, exenatide extended release 2.0 mg, insulin glargine 100 IU/ml, and dulaglutide 0.75 or 1.5 mg). Outcomes measured included change in HbA1c and body weight from baseline to weeks 30, 40 and 104, and other efficacy and safety endpoints.

Across race and ethnicity subgroups, semaglutide 0.5 and 1.0 mg significantly reduced HbA1c from 1.0 at baseline to 1.5 percentage points and from 1.3 to 2.0 percentage points, and body weight by 2.3–4.7 kg and 3.6–6.1 kg, respectively. In addition, there were slight changes seen in both blood pressure and lipid profiles. [J Clin Endocrinol Metab 2020;105:dgz072]

“These findings are aligned with those from the individual phase IIIa SUSTAIN trials, in which semaglutide provided superior reductions in HbA1c and body weight vs placebo and active comparators (sitagliptin, exenatide ER, insulin glargine and dulaglutide),” the researchers said. [Lancet Diabetes Endocrinol 2017;5:251-260; Lancet Diabetes Endocrinol 2017;5:341-354; Diabetes Care 2018;41:258-266; Lancet Diabetes Endocrinol 2017;5:355-366; J Clin Endocrinol Metab 2018;103:2291-2301; Lancet Diabetes Endocrinol 2018;6:275-286]

Furthermore, incidence of adverse events (AEs) was similar across trials. Compared with other race subgroups, more Asians prematurely discontinued treatment due to AEs. Gastrointestinal (GI) disorders, such as diarrhoea, vomiting and constipation, were the most commonly reported AEs.

“GI AEs … and AEs leading to premature treatment discontinuation were slightly higher in Asians than in other races,” the researchers said. “The lower body weight in Asian [patients] at baseline may have contributed to these in SUSTAIN 1–5 and 7.”

These findings may have been driven by differences in the Asian culture and diet, as well as lower baseline weight in the Asian subgroup compared with other races and ethnicities. [Diabetes Obes Metab 2018;20:378-388; Diabetes Obes Metab 2018;20:1202-1212]

Semaglutide, in general, was well tolerated across race and ethnicity subgroups, with a safety profile similar to that of other glucagon-like peptide-1 receptor agonists, the researchers said. [J Fam Pract 2018;67(6 suppl):S25-S34]

Certain limitations were present, according to the researchers. First, the SUSTAIN trials were not designed to assess the effect of race and ethnicity on semaglutide treatment. Second, posthoc analyses were limited by their retrospective nature. Third, not all ethnicity subgroups or countries with multiple race and ethnicity groups were represented.