Efficacy of Dapagliflozin + Sitagliptin + Metformin Versus Sitagliptin + Metformin in T2DM Inadequately Controlled on Metformin Monotherapy: A Multicentric Randomized Trial

Awadhesh Kumar Singh; Ashok Kumar Das; L Sreenivasa Murthy; Samit Ghosal; Rakesh Sahay; K V S Harikumar; Ganesh Hosahithlu Keshava; Mayur Agarwal; G Vijayakumar; Pramila Kalra; Piyush Lodha; Sambit Das; Shehla Shaikh; Soumik Goswami; T P Ajish; Prashant Kumthekar; Mihir Upadhyay; Anthuvan Thamburaj; Aushili Mahule; Ashish Prasad; Abhijit Pednekar

doi:10.1007/s12325-024-03037-y

Efficacy of Dapagliflozin + Sitagliptin + Metformin Versus Sitagliptin + Metformin in T2DM Inadequately Controlled on Metformin Monotherapy: A Multicentric Randomized Trial

Adv Ther. 2024 Dec 5. doi: 10.1007/s12325-024-03037-y. Online ahead of print.

Authors

Awadhesh Kumar Singh¹, Ashok Kumar Das², L Sreenivasa Murthy³, Samit Ghosal⁴, Rakesh Sahay⁵, K V S Harikumar⁶, Ganesh Hosahithlu Keshava⁷, Mayur Agarwal⁸, G Vijayakumar⁹, Pramila Kalra¹⁰, Piyush Lodha¹¹, Sambit Das¹², Shehla Shaikh¹³, Soumik Goswami¹⁴, T P Ajish¹⁵, Prashant Kumthekar¹⁶, Mihir Upadhyay¹⁶, Anthuvan Thamburaj¹⁷, Aushili Mahule¹⁷, Ashish Prasad¹⁷, Abhijit Pednekar¹⁷

Affiliations

¹ GD Hospital and Diabetes Institute, 139 A, Lenin Sarani Rd, Bowbazar, Kolkata, West Bengal, 700013, India. drawadheshkumarsingh@gmail.com.
² Mahatma Gandhi Medical College, Cuddalore Rd, ECR, Pillayarkuppam, Puducherry, 607402, India.
³ Lifecare Hospital and Research Centre, 2748/2152, M.L.N Complex, 16th E Cross, 8th Main Rd, Next to Union Bank of India, D Block, Bangalore, Karnataka, 560092, India.
⁴ Nightingale Hospital, 11, Shakespeare Sarani Rd, Kankaria Estates, Park Street Area, Kolkata, West Bengal, 700071, India.
⁵ Osmania General Hospital, 15-5-104, Begum Bazar, Afzal Gunj, Hyderabad, Telangana, 500012, India.
⁶ Fernandez and Magna Clinics, D-4, Rd Number 9, Durga Bhawani Nagar, MLA Colony, Film Nagar, Hyderabad, Telangana, 500033, India.
⁷ AJ Hospital, NH 66, Kuntikana, Mangalore, Karnataka, 575004, India.
⁸ Hormone India Center Bhopal and SAGE Apollo, Bawadiya Kalan, Salaiya, Bhopal, Madhya Pradesh, 462026, India.
⁹ Diabetes Medicare Centre, 19, Flat New 8, Rams Tower, Raja St, Pondy Bazaar, T. Nagar, Chennai, Tamil Nadu, 600017, India.
¹⁰ Ramaiah Medical College and Hospital, New BEL Rd, MS Ramaiah Nagar, Mathikere, Bangalore, Karnataka, 560054, India.
¹¹ Ruby Hall Clinic, 40, Sasoon Rd, Sangamvadi, Pune, Maharashtra, 411001, India.
¹² Department of Endocrinology, Kalinga Institute of Medical Sciences (KIMS), 5, KIIT Rd, Bhubaneswar, Odisha, 751024, India.
¹³ Saifee Hospital, Maharshi Karve Rd, Opp. Charni Road, Charni Road East, Opera House, Girgaon, Mumbai, Maharashtra, 400004, India.
¹⁴ NRS Medical College, 138, Acharya Jagdish Chandra Bose Rd, Sealdah, Raja Bazar, Kolkata, West Bengal, 700014, India.
¹⁵ Travancore Medical College Hospital, N H Bypass Mylapore, Thattamala, P. O, Kollam, Kerala, 691020, India.
¹⁶ Indian Society of Clinical Research, The Capital, 1802, 18th Floor, Plot No. C-70, 'G' Block, Bandra Kurla Complex, Bandra (E), Mumbai, 400 051, India.
¹⁷ USV Pvt Ltd, Mumbai, Arvind Vithal Gandhi Chowk, BSD Marg, Station Road, Govandi East, Mumbai, 400 088, India.

PMID: 39636567
DOI: 10.1007/s12325-024-03037-y

Abstract

Introduction: A slower adoption rate of fixed dose combinations (FDC) in diabetes management is partly due to insufficient data. This study evaluates the safety and efficacy of an FDC of dapagliflozin + sitagliptin + metformin hydrochloride extended release (XR), compared to a dual FDC of sitagliptin + metformin hydrochloride XR among patients with type 2 diabetes mellitus (T2DM) with poor glycemic control when treated with metformin monotherapy.

Methods: A total of 274 patients with T2DM were randomized (1:1) to either arm X, receiving FDC of dapagliflozin (10 mg) + sitagliptin (100 mg) + metformin hydrochloride XR (1000 mg) (Dapa + Sita + Met) tablets, or arm Y, receiving sitagliptin phosphate (100 mg) + metformin hydrochloride XR (1000 mg) (Sita + Met) tablets, and treated for 16 weeks. The outcome measures included changes in hemoglobin A1c (HbA1c)(%), fasting plasma glucose (FPG), 2-h post-prandial glucose (PPG), weight, and the proportion of patients achieving target HbA1c levels of < 7.0% by week 16 of the study period.

Results: The reduction in HbA1c at week 16 was significantly higher in arm X than in arm Y [estimated treatment difference (ETD), - 0.65% (95% CI - 0.76 to - 0.53; P < 0.0001)]. Arm X showed a marked decrease in FPG [ETD - 15.42 mg/dl; 95% CI (17.63, 13.22; P < 0.0001)], PPG [ETD - 30.39 mg/dl; 95% CI (35.59, 25.19; P < 0.0001)], and weight [ETD - 1.47 kg; 95% CI (1.59, 1.28; P < 0.0001)] after 16 weeks. In arm X, 54% of patients reached HbA1c < 7.0% compared to 29.9% in arm Y. The incidence of adverse events was comparable [13.14% (arm X) vs 12.4% (arm Y)]. There was no severe hypoglycemia-led treatment discontinuation.

Conclusion: Among patients with T2DM who have poor glycemic control with metformin monotherapy, triple FDC (Dapa + Sita + Met) effectively helped achieve better glycemic response compared to dual FDC (Sita + Met), with a comparable safety and tolerability profile.

Trial registration: CTRI/2022/01/039857.

Keywords: Dapagliflozin; Metformin; Sitagliptin; Triple fixed dose combination; Type 2 diabetes.