Once-Weekly Semaglutide Bests Empagliflozin for HbA1c Control and Weight Loss


Using data from a group of RCTs, investigators determined semaglutide was associated with greater reductions in HbA1c and weight loss than empagliflozin.

hba1c testing

Results of a recent study incorporating data from 4 randomized clinical trials is shedding light on the effectiveness of once-weekly semaglutide versus empagliflozin as add-on therapies to metformin in patients with type 2 diabetes.

Despite no head-to-head trials directly comparing the GLP1-RA to the SGLT2 inhibitor, results of the latest study indicate once-weekly semaglutide was associated with greater HbA1c control and reductions in body weight compared against empagliflozin.

“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 type 2 diabetes when added to metformin monotherapy,” wrote study investigators.

With no trials offering a direct comparison of the popular anti diabetes medications, a team representing UT Southwestern Medical Center, the Rotherham Institute for Obesity, and Novo Nordisk sought to offer clinicians a reliable comparison of the two agents. To do so, investigators designed an indirect comparison of patient-level data from the SUSTAIN 2, SUSTAIN 3, SUSTAIN 8, and PIONEER 2 trials.

From these trials, investigators identified cohorts of 995 patients receiving semaglutide and 410 patients receiving empagliflozin. Of the 995 receiving semaglutide, 388 were from SUSTAIN 2, 213 were from SUSTAIN 3, and 394 were from SUSTAIN 8. All patients receiving empagliflozin in PIONEER 2 were included in the current analysis. Investigators pointed out baseline characteristics were similar between both the empagliflozin and semaglutide groups and the 3 SUSTAIN trials included in the analysis.

The primary efficacy outcomes for the analysis were change from baseline to end of treatment in HbA1c and body weight. Other outcomes of interest in the analysis included the proportion of patients achieving HbA1c targets, weight-loss responses, and composite responder outcomes. Of note, investigators also examined other relevant measures of efficacy such as hang from baseline to end of treatment in BMI, waist circumference, systolic and diastolic blood pressure, lipid parameters, and eGFR.

Upon analysis, results indicated once-weekly semaglutide was associated with a significantly lowered mean HBA1c when compared against empagliflozin (Estimated treatment difference: –0.61%; 95% CI, -0.72 to -0.49). Similarly, once-weekly semaglutide was also associated with significantly reduced mean body weight compared to empagliflozin (Estimated treatment difference, -1.65 kg; 95% CI, -2.22 to -1.08; P <.0001).

In regard to responder outcomes, a significantly greater proportion of patients on semaglutide than empagliflozin achieved HbA1c targets of 7% or less (69.1% vs 39.3%; OR, 4.37; 95% CI, 3.33-5.74; P <.0001) and 6.5% (54.2% vs 19.0%; OR, 5.99; 95% CI, 4.46-8.05; P <.0001). Investigators noted similar results when examining weight loss outcomes. Specifically, a significantly greater proportion of patients receiving semaglutide compared against empagliflozin achieved weight-loss responses of 5% or more and 10% or more (20.6% vs 7.3%; OR: 3.80; 95% CI, 2.53-5.71; P <.0001).

Additionally, a significantly greater proportion of patients on semaglutide rather than empagliflozin achieved HbA12c reduction of 1% or more and weight loss of 5% or more, HbA1c less than 7.0% and a weight loss of 5% or more, and an HbA1c of less than 7.0% with no severe or blood glucose-confirmed hypoglycemia and no weight gain (all P <.0001).

“The findings presented here align with a previously published indirect comparison with shorter follow-up times and provide additional results on clinically relevant measures of efficacy not previously assessed and may provide additional evidence to inform treatment decisions,” wrote study investigators.

This study, “Efficacy of once-weekly semaglutide vs empagliflozin added to metformin in type 2 diabetes: patient-level meta-analysis,” was published in the Journal Of Clinical Endocrinology and Metabolism.

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