Diabetes Metab J.  2023 Nov;47(6):796-807. 10.4093/dmj.2022.0315.

Efficacy and Safety of Enavogliflozin versus Dapagliflozin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus: A 24-Week, Double-Blind, Randomized Trial

• Han KA
• Kim YH
• Kim DM
• Lee BW
• Chon S
• Sohn TS
• Jeong IK
• Hong EG
• Son JW
• Nah JJ
• Song HR
• Cho SI
• Cho SA
• Yoon KH

• KMID: 2548156
• DOI: http://doi.org/10.4093/dmj.2022.0315

Abstract

Background
Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin.
Methods
In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500).
Results
Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated.
Conclusion
Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone.

Keyword

Dapagliflozin; Diabetes mellitus, type 2; Hypoglycemic agents; Metformin; Randomized controlled trial; Sodium-glucose transporter 2 inhibitors

Figure

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  Fig. 1. Study flowchart.

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  Fig. 2. Changes in efficacy parameters over time. Line graphs show adjusted mean changes from baseline in (A) glycosylated hemoglobin (HbA1c), (B) fasting plasma glucose (FPG), (C) systolic blood pressure (SBP), (D) diastolic blood pressure (DBP), and (E) body weight. Error bars represent the standard error of the mean. SE, standard error of mean. aP≤0.001, bP<0.0001, footnotes denote a statistically significant change from baseline.

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  Fig. 3. Percentage of patients reaching target glycosylated hemoglobin (HbA1c). (A) Percentage of patients reaching HbA1c <7.0%. (B) Percentage of patients achieving therapeutic glycemic response, defined as HbA1c reduction >0.5% or HbA1c <7.0%. The odds ratios shown above the top square brackets represent the odds of achieving each of the defined glycemic responses in the enavogliflozin group to that in the dapagliflozin group. No statistically significant difference in the odds of achieving either of the glycemic responses was found between the two groups. The 95% confidence intervals of all the calculated odd ratios included 1, and all P values were >0.05.

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