Endocrinol Metab.  2023 Jun;38(3):328-337. 10.3803/EnM.2023.1688.

Efficacy of Gemigliptin Add-on to Dapagliflozin and Metformin in Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Study (SOLUTION)

• Lee BW
• Min K
• Hong EG
• Ku BJ
• Kang JG
• Chon S
• Lee WY
• Park MK
• Kim JH
• Kim SY
• Song K
• Yoo SJ

• KMID: 2543319
• DOI: http://doi.org/10.3803/EnM.2023.1688

Abstract

Background
This study evaluated the efficacy and safety of add-on gemigliptin in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with metformin and dapagliflozin.
Methods
In this randomized, placebo-controlled, parallel-group, double-blind, phase III study, 315 patients were randomized to receive either gemigliptin 50 mg (n=159) or placebo (n=156) with metformin and dapagliflozin for 24 weeks. After the 24-week treatment, patients who received the placebo were switched to gemigliptin, and all patients were treated with gemigliptin for an additional 28 weeks.
Results
The baseline characteristics were similar between the two groups, except for body mass index. At week 24, the least squares mean difference (standard error) in hemoglobin A1c (HbA1c) changes was –0.66% (0.07) with a 95% confidence interval of –0.80% to –0.52%, demonstrating superior HbA1c reduction in the gemigliptin group. After week 24, the HbA1c level significantly decreased in the placebo group as gemigliptin was administered, whereas the efficacy of HbA1c reduction was maintained up to week 52 in the gemigliptin group. The safety profiles were similar: the incidence rates of treatment-emergent adverse events up to week 24 were 27.67% and 29.22% in the gemigliptin and placebo groups, respectively. The safety profiles after week 24 were similar to those up to week 24 in both groups, and no new safety findings, including hypoglycemia, were noted.
Conclusion
Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin.

Keyword

Dipeptidyl-peptidase IV inhibitors; Gemigliptin; Sodium-glucose transporter 2 inhibitors; Dapagliflozin; Metformin; Diabetes mellitus, type 2

Figure

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  Fig. 1. Disposition. aSafety set includes all randomized patients administered with the investigational product (placebo or gemigliptin) at least once; bFull analysis set includes patients in the safety set with hemoglobin A1c level measured at baseline and at least once after

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  Fig. 2. (A) Change of hemoglobin A1c (HbA1c) over time from baseline–full analysis set. (B) Change of fasting plasma glucose (FPG) over time from baseline–full analysis set. LS, least square; SE, standard error. aP<0.0001 vs. placebo.

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  Fig. 3. (A) Adjusted responder rate (hemoglobin A1c [HbA1c] <7%) at week 24–full analysis set. (B) Adjusted response rate (HbA1c <6.5%) at week 24–full analysis set. (C) Adjusted response rate (HbA1c <7%) at week 52–full analysis set. (D) Adjusted response rate (HbA1c <6.5%) at week 52–full analysis set. OR, odds ratio; CI, confidence interval. aLogistic regression model including group as a factor and HbA1c and estimated glomerular filtration rate values as covariates.

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