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Clinical Trial
. 2025 Apr;27(4):2193-2205.
doi: 10.1111/dom.16218. Epub 2025 Feb 14.

Fixed dose combination of dapagliflozin, glimepiride and extended-release metformin tablets in patients with type 2 diabetes poorly controlled by metformin and glimepiride: A phase III, open label, randomized clinical study in India

Rakesh Sahay  1 , Dinesh Gangwani  2 , Manish Singh  3 , Sandeep Gupta  4 , Narendra Kale  5 , Manoj Srivastava  6 , Prakash Kurmi  7 , Jayesh Ambaliya  8 , Nilesh Lomte  9 , Sandip Gofne  10 , Saurabh Agarwal  11 , Priyanka Kashid  12 , Vikas Agarwal  13 , Pradeep Rai  14 , Surendra Sharma  15 , L Sreenivasa Murthy  16 , Mandodari Rajurkar  17 , Shruti Saha  17 , Piyush Patel  17 , Dipak Patil  17 , Pravin Ghadge  17 , Lalit Lakhwani  17 , Suyog Mehta  17 , Sadhna J Joglekar  18
Affiliations
Clinical Trial

Fixed dose combination of dapagliflozin, glimepiride and extended-release metformin tablets in patients with type 2 diabetes poorly controlled by metformin and glimepiride: A phase III, open label, randomized clinical study in India

Rakesh Sahay et al. Diabetes Obes Metab. 2025 Apr.

Abstract

Aim: To evaluate the efficacy and safety of a triple fixed-dose combination (FDC) therapy of dapagliflozin + glimepiride + metformin hydrochloride extended-release (DAPA + GLIM + MET ER) tablets in Indian patients with type 2 diabetes mellitus (T2DM) inadequately controlled by combination of GLIM + MET.

Materials and methods: A phase III, randomized, open-label, active-controlled study was conducted for a maximum 30 weeks (primary treatment [16 weeks]; uptitration [12 weeks] and follow-up [2 weeks]). Eligible patients were randomized in a 1:1 ratio to receive either the FDC of DAPA + GLIM + MET ER or the FDC of GLIM + MET prolonged-release (PR) once-daily. The primary efficacy endpoint was a change in glycated haemoglobin (HbA1c) from baseline to week 16.

Results: The mean reduction in HbA1c from baseline to week 16 was significantly greater with the FDC of DAPA + GLIM + MET ER compared to the FDC of GLIM + MET PR (-1.98% ± 1.01% vs. -1.64% ± 0.86%, p = 0.0047). The mean reduction in HbA1c from baseline to week 12 was significantly greater with the FDC of DAPA + GLIM + MET ER versus dual FDC (p < 0.0001). The proportion of patients achieving HbA1c <7.0% was significantly greater with the FDC of DAPA + GLIM + MET ER versus dual FDC at week 12 (19.1% vs. 6.5%; p = 0.0002) and week 16 (52.6% vs. 36.7%; p = 0.0015). A significant decrease in HbA1c, fasting and post-prandial blood glucose from baseline to weeks 12, 16, and 28 was observed in both arms. The incidence of TEAEs was similar across both arms.

Conclusion: This study demonstrated that the FDC of DAPA + GLIM + MET ER tablets once daily was significantly better than dual FDC in achieving glycaemic control in patients with poorly controlled T2DM. Both treatments were well-tolerated.

Trial registration: CTRI/2022/03/041424, registered on 28 March 2022.

Keywords: SGLT2 inhibitor; dapagliflozin; fixed‐dose combination; glycaemic profile; metformin; type 2 diabetes.

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Conflict of interest statement

Authors, Rakesh Sahay, Dinesh Gangwani, Manish Singh, Sandeep Gupta, Narendra Kale, Manoj Srivastava, Prakash Kurmi, Jayesh Ambaliya, Nilesh Lomte, Sandip Gofne, Saurabh Agarwal, Priyanka Kashid, Vikas Agarwal, Pradeep Rai, Surendra Sharma, L. Sreenivasa Murthy were the study investigators and they received a grant from sponsor for conducting the study at their respective sites and declare no conflict of interests. Mandodari Rajurkar, Shruti Saha, Dipak Patil, Pravin Ghadge and Suyog Mehta are full‐time employees of Sun Pharma Laboratories Ltd. Dr. Piyush Patel and Dr. Lalit Lakhwani were full‐time employees of Sun Pharma Laboratories Ltd. during the conduct of the study. Dr. Sadhna J. Joglekar was a full‐time employee of Sun Pharmaceutical Industries Ltd. during conduct of the study.

Figures

FIGURE 1
FIGURE 1
Study design. D, day; DAPA, dapagliflozin; EOS, end of study; EOS, end of study; EOT, end of treatment; ER, extended‐release; FDC, fixed‐dose combination; GLIM, glimepiride; HbA1c, glycated haemoglobin; MET, metformin; OD, once‐daily; PR, prolonged release; SR, sustained release; V, Visit; Wk, week. *For patients achieving HbA1c ≤7.0% at the end of week 16, EOT assessments were carried out at week 16 and EOS at week 18. **For patients achieving HbA1c >7.0% and entering the uptitration period, EOT assessments were carried out at week 28 and EOS at week 30.
FIGURE 2
FIGURE 2
Patient disposition (CONSORT). DAPA, dapagliflozin; EOS, end of study; EOT, end of treatment; ER, extended‐release; FDC, fixed‐dose combination; GLIM, glimepiride; HbA1c, Glycated Haemoglobin; MET, metformin; PR, prolonged release. Post primary treatment period of 16 weeks, for patients with HbA1c level ≤7%, EOT assessments were performed at end of week 16 and were monitored for safety at week 18 (EOS). Post primary treatment period of 16 week, patients with HbA1c level >7% entered the uptitration period (week 17 to week 28). Patients who required uptitration were followed up for safety assessments at week 30 (EOS).
FIGURE 3
FIGURE 3
Change in HbA1c (%) from baseline to weeks 12 and 16. DAPA, dapagliflozin; ER extended release; FDC, fixed‐dose combination; GLIM, glimepiride; HbA1c, glycated haemoglobin; MET, metformin; PR, prolonged release. Rank ANCOVA model for change in HbA1c as the dependent variable, treatment, and treatment‐by‐visit interaction as fixed effects, and baseline HbA1c as a covariate.
FIGURE 4
FIGURE 4
Proportion of patients achieving HbA1c <7.0% at week 12 and week 16. DAPA, dapagliflozin; ER, extended release; FDC, fixed‐dose combination; GLIM, glimepiride; HbA1c, glycated haemoglobin; MET, metformin; PR, prolonged release. p‐value was estimated using Chi‐square test for between‐group comparison. Percentage was computed using total number of subjects in each visit.
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