Emerging use of combination therapies for the management of type 2 diabetes &amp;ndash; focus on saxagliptin and dapagliflozin

Yu, Haiming; Woo, Vincent

doi:10.2147/dmso.s117982

Cited by 12 publications

(12 citation statements)

References 100 publications

(329 reference statements)

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“…In the experimental animal studies, SGLT2 showed anti-atherosclerotic effects through anti-oxidant effects 6) . Further, SGLT2 and DPP4 showed synergic effects on the anti-atherosclerotic effect in the experimental study 16,17) , and the preliminary clinical study [18][19][20] . Intestinal sodium glucose cotransporter-1 inhibition was reported to enhance glucagon-like peptide-1 (GLP-1) secretion in normal and diabetic rodents 21) .…”

Section: Discussionmentioning

confidence: 86%

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Effect of Canagliflozin on endothelial function in diabetic patients with suspected coronary artery disease: retrospective preliminary pilot study

2018

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Background: Sodium-glucose transporter-2 inhibitor (SGLT2) is reported to have anti-atherosclerotic effects in experiment. However, the effect of SGLT2 on endothelial function (ECF) in humans is not fully investigated. Method and Results: We measured ECF in 11 diabetic patients with coronary artery disease (CAD) and poor control of diabetics (HbA1c >7%; 75 8 years old) by simultaneously measuring brachial artery flow-mediated dilation (FMD) and EndoPAT2000 (measuring RHI). FMD and RHI were measured before and after mean periods of 4-week treatment of Canagliflozin (100 mg per every other day).

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Section: Discussionmentioning

confidence: 86%

“…In the real world, SGLT2 is frequently added to DM patients similar to this study 20) . And preliminary clinical study showed that the combination therapies of DPP4 and SGLT2 seem to be effective in the treatment of patients with type 2 DM 19,20) . These findings are similar to our results.…”

Section: Discussionmentioning

confidence: 99%

Effect of Canagliflozin on endothelial function in diabetic patients with suspected coronary artery disease: retrospective preliminary pilot study

2018

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“…The function of DPP‐4is with sulphonylurea mechanistically relies on residual β‐cell activity, while SGLT‐2is work complementarily to DPP4is, reducing hyperglycaemia through renal excretion of glucose, independent of insulin secretion, thus reducing glucotoxicity and β‐cell burden. The risk of genital infections with combination therapy is lower than that observed with DAPA alone, which is suggestive of a protective effect …”

Section: Discussionmentioning

confidence: 89%

“…Studies have reported that the sodium‐glucose cotransporter‐2 inhibitor (SGLT‐2i) dapagliflozin (DAPA) plus the dipeptidyl peptidase‐4 inhibitor (DPP‐4i) saxagliptin (SAXA) in combination with metformin provides superior HbA1c reductions versus either agent added to metformin alone, with a lower risk of hypoglycaemia and BW gain . The risk of genital infection is lower in treatment regimens with the combination of DAPA + SAXA than DAPA monotherapy . However, validation is needed to determine the long‐term efficacy of DAPA + SAXA versus injectable insulin as an add‐on to metformin therapy in patients with T2D.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of dapagliflozin plus saxagliptin versus insulin glargine over 52 weeks as add‐on to metformin with or without sulphonylurea in patients with type 2 diabetes: A randomized, parallel‐design, open‐label, Phase 3 trial

Vilsbøll

Ekholm

Johnsson

et al. 2020

Diabetes Obesity Metabolism

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Aim: Efficacy and safety of dapagliflozin plus saxagliptin (DAPA + SAXA) were compared with insulin glargine (INS) in patients with type 2 diabetes (T2D) in a 52-week extension study. Materials and methods: This international Phase 3 study randomized adults with T2D on metformin with/without sulphonylurea. They received DAPA + SAXA or INS for 24 weeks (short-term) with a 28-week (long-term) extension. Week 52 exploratory endpoints included adjusted mean change from baseline in glycated haemoglobin A 1c (HbA1c) and body weight, and a proportion of patients achieving optimal glycaemic response without hypoglycaemia and without requiring rescue medication. Results: Of the 1163 patients enrolled, 643 received treatment; 600 (DAPA + SAXA, 306; INS, 294) entered the long-term phase. At 52 weeks, HbA1c [adjusted least squares (LS) mean; 95% confidence interval (CI)] decreased more with DAPA + SAXA (−1.5% [−1.6%, −1.4%]) than with INS (−1.3% [−1.4%, −1.1%]); the LS mean difference (95% CI) was −0.25% (−0.4%, −0.1%; P = 0.009). Total body weight reduced with DAPA + SAXA [LS mean (95% CI): −1.8 kg (−2.4, −1.3)] and increased with INS [LS mean (95% CI): +2.8 kg (2.2, 3.3)]. More patients on DAPA + SAXA (17.6%) achieved HbA1c <7.0% without hypoglycaemia versus those on INS (9.1%). Rescue medication was required by 77 patients (23.8%) and 97 patients (30.4%) in the DAPA + SAXA and INS groups, respectively. Conclusion: DAPA + SAXA treatment was non-inferior to INS in reducing HbA1c and body weight, and in achieving optimal glycaemic control without hypoglycaemia in patients with T2D 52 weeks after initiation. K E Y W O R D S combination therapy, dapagliflozin, insulin glargine, saxagliptin, type 2 diabetes An abstract of this work has been presented as a poster at

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“…[1112] Improvement in glycaemic control with combination of saxagliptin and metformin is established for better tolerance without the incidence of weight gain. [1314] Moreover, this combination poses improvement in quality-adjusted life-years (QALYs) apart from its effectiveness and cost-effectiveness. [151617]…”

Section: Introductionmentioning

confidence: 99%

Therapeutic experience of saxagliptin as first add-on after metformin in Indian type 2 diabetes patients: A non-interventional, prospective, observational study (ONTARGET-INDIA)

Kalra

Bajaj

Unnikrishnan³

et al. 2019

Indian J Endocr Metab

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Introduction: Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used in type 2 diabetes mellitus (T2DM) patients but the data available in existing clinical trial programmes on DPP4 inhibitors include limited number of patients from India. Hence, this study attempted to understand usage, efficacy and safety of saxagliptin as first add-on after metformin in Indians with T2DM. Methodology: It was a multicenter, prospective, non-interventional and observational study planned to enrol T2DM patients who were inadequately controlled with metformin alone and had been recently (i.e., within past 15 days) prescribed saxagliptin as an add-on to metformin. Type 1 diabetes mellitus, use of glucose lowering drugs apart from metformin or saxagliptin, pregnancy, lactation, and medical condition, which could interfere with safe completion of the study were excluded. Results: A total of 1109 participants (658 men and 451 women) with mean ± SD age of 51.17 ± 11.85 years were enrolled from 50 centres throughout India. Significant reduction was observed in mean ± SD change of HbA1c as − 0.86% ± 1.76 from baseline to after 3 months of therapy ( P < 0.0001). The quality of life assessed by World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire was reported to be “good” or “neither good nor bad” by majority of the participants at baseline and after 3 months of treatment. A total of 15 adverse events (AEs) were reported in the study, however, no serious adverse event (SAE) occurred during the study. All AEs were of mild intensity and did not require any intervention. Conclusion: Overall, saxagliptin in combination with metformin was generally well tolerated in Indian T2DM patients and new safety event identified is an increased risk of hospitalisation in heart failure patients. This study is also registered on Clinicaltrials.gov (NCT02588859).

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Emerging use of combination therapies for the management of type 2 diabetes – focus on saxagliptin and dapagliflozin

Cited by 12 publications

References 100 publications

Effect of Canagliflozin on endothelial function in diabetic patients with suspected coronary artery disease: retrospective preliminary pilot study

Effect of Canagliflozin on endothelial function in diabetic patients with suspected coronary artery disease: retrospective preliminary pilot study

Efficacy and safety of dapagliflozin plus saxagliptin versus insulin glargine over 52 weeks as add‐on to metformin with or without sulphonylurea in patients with type 2 diabetes: A randomized, parallel‐design, open‐label, Phase 3 trial

Therapeutic experience of saxagliptin as first add-on after metformin in Indian type 2 diabetes patients: A non-interventional, prospective, observational study (ONTARGET-INDIA)

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