Once Weekly Semaglutide Reduced Mean HbA1c vs Empagliflozin

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Once weekly semaglutide provided superior glycemic control compared with empagliflozin when added to metformin monotherapy in uncontrolled T2D.

Once weekly semaglutide (1 mg) provided superior glycemic control and weight reduction compared with empagliflozin (25 mg) when added to metformin monotherapy in uncontrolled type 2 diabetes, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors are recommended as second line treatment options for patients with type 2 diabetes receiving metformin monotherapy, or as first-line treatments in those at high cardiovascular risk.

The aim of the current study was to compare the efficacy of both agents as an add-on to metformin monotherapy in patients with uncontrolled type 2 diabetes.

Researchers used individual patient data for those with type 2 diabetes receiving metformin monotherapy that were randomized to receive either once-weekly semaglutide  (SUSTAIN 2, 3, 8 trials) or to empagliflozin (PIONEER 2 trial). The changes in glycated hemoglobin A1c (HbA1c) and body weight from baseline to end of treatment were assessed.

The primary efficacy analyses included 995 patients taking once-weekly semaglutide 1 mg and 410 patients receiving empagliflozin 25 mg. At baseline, patient characteristics were similar in both groups.

The indirect analysis showed that at the end of treatment, once-weekly semaglutide 1 mg was superior to empagliflozin 25 mg in reducing HbA1c (1.44%-point vs 0.83%-point, respectively; P < .0001) and lowering body weight (5.29 kg vs 3.64 kg, respectively; P < .0001). Complementary analyses supported these findings.

Furthermore, a greater proportion of patients treated with semaglutide achieved clinically relevant HbA1c targets and weight loss responses.

Semaglutide may be advantageous to empagliflozin across additional clinically relevant measures of efficacy, including body mass index, waist circumference, total cholesterol, and triglyceride levels. However, empagliflozin was superior to semaglutide in reducing diastolic blood pressure and increasing high-density lipoprotein. No difference was evident between the groups with regard to systolic blood pressure or estimated glomerular filtration rate.

The study had several limitations, including the unanchored analysis approach, some inter-trial differences, and lack of assessment of the safety profiles of the medications.

“This indirect comparison suggests that [once weekly] semaglutide 1 mg provides superior reductions in HbA1c and body weight, as well as across other measures of efficacy, including BMI, waist circumference and some lipid parameters, vs [once daily] empagliflozin 25 mg in patients with T2D when added to metformin monotherapy,” concluded the researchers.

Disclosure: This clinical trial was supported by Novo Nordisk A/S, Denmark. Multiple study authors have disclosed receiving financial support from pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.


Lingvay I, Capehorn MS, Catarig AM, et al. Efficacy of once-weekly semaglutide vs. empagliflozin added to metformin in type 2 diabetes: patient-level meta-analysis. Published online Aug 22, 2020. J Clin Endocrinol Metab. doi: 10.1210/clinem/dgaa577