Semaglutide Better Controls HbA1C and Weight Outcomes in Type 2 Diabetes

Once-daily semaglutide significantly reduces glycated hemoglobin (HbA_1C) levels and body weight in a dose-dependent manner among patients with type 2 diabetes (T2D), according to study findings published in Diabetes Research and Clinical Practice.

Researchers from Southern Medical University in China conducted a systematic review and meta-analysis and searched publication databases through May 2021 for randomized controlled trials evaluating HbA_1C and body weight outcomes from oral semaglutide therapy.

A total of 11 trials, which were all of multicenter designs, conducted in multiple countries (n=9) or Japan (n=2) and published between 2017 and 2020 were included in the final analysis.

The pooled study population included 9821 participants who received oral semaglutide 5 to 14 mg, dulaglutide 0.75 mg, liraglutide 0.9 or 1.8 mg, empagliflozin 25 mg, sitagliptin 100 mg, or placebo.

Compared with placebo, semaglutide 7 mg (mean difference [MD], -1.06%; 95% CI, -1.30% to -0.81%; I², 72%; P <.00001) and 1 semaglutide 4 mg (MD, -1.10%; 95% CI, -1.31% to -0.88%; I², 89%; P <.00001) were associated with significant improvements to HbA_1C levels.

Compared with active comparators, semaglutide 7 mg was favored over sitagliptin (MD, -0.30%; 95% CI, -0.43% to -0.17%; P <.00001). Semaglutide 14 mg was favored over sitagliptin (MD, -0.50%; 95% CI, -0.60% to -0.40%; I², 0%; P <.00001), empagliflozin (MD, -0.40%; 95% CI, -0.54% to -0.26%; P <.00001), and dulaglutide (MD, -0.40%; 95% CI, -0.68% to -0.12%; P =.005) for lowering HbA_1C levels.

The odds of achieving a HbA_1C level of 7.0% or less was increased with semaglutide 7 mg (risk ratio [RR], 3.36; 95% CI, 2.05-5.51; I², 80%) or semaglutide 14 mg (RR, 3.67; 95% CI, 2.49-5.39; I², 82%) compared with placebo.

Regarding body weight outcomes, both semaglutide 7 mg (MD, -1.18; 95% CI, -2.13 to -0.23 kg; I², 76%; P =.01) and semaglutide 14 mg (MD, -2.96; 95% CI, -3.49 to -2.42 kg; I², 72%; P <.00001) were favored over placebo.

Compared with active comparators, semaglutide 7 mg was favored over the 3 evaluated medications—sitagliptin, liraglutide, and dulaglutide (MD, -1.47; 95% CI, -1.81 to -1.12 kg; I², 0%; P <.00001). Semaglutide 14 mg was favored over dulaglutide (MD, -2.50; 95% CI, -3.26 to -1.74 kg; P <.00001), sitagliptin (MD, -2.31; 95% CI, -2.79 to -1.84 kg; I², 32%; P <.00001), and liraglutide (MD, -1.80; 95% CI, -3.07 to -0.53 kg; I², 77%; P =.006), but not empagliflozin for its body weight-lowering effect.

Limitations of the study include the high heterogeneity observed in some comparisons and the lack of data from multiple trials for some of the comparisons.

The researchers conclude, “[O]nce-daily 14 mg oral semaglutide can significantly reduce HbA_1c, body weight and a higher proportion of patients achieving blood glucose goals when compared to either placebo or other antidiabetic agents.”