Emerging use of combination therapies for the management of type 2 diabetes – focus on saxagliptin and dapagliflozin (original) (raw)
Related papers
Diabetes care, 2015
To compare the efficacy and safety of treatment with dapagliflozin versus that with placebo add-on to saxagliptin plus metformin in patients whose type 2 diabetes is inadequately controlled with saxagliptin plus metformin treatment. Patients receiving treatment with stable metformin (stratum A; screening HbA1c level 8.0-11.5% [64-102 mmol/mol]) or stable metformin and a dipeptidyl peptidase-4 (DPP-4) inhibitor (stratum B; HbA1c 7.5-10.5% [58-91 mmol/mol]) for ≥8 weeks received open-label saxagliptin 5 mg/day and metformin for 16 weeks (stratum A) or 8 weeks (stratum B, saxagliptin replaced any DPP-4 inhibitor). Patients with inadequate glycemic control (HbA1c 7-10.5% [53-91 mmol/mol]) were randomized to receive placebo or dapagliflozin 10 mg/day plus saxagliptin and metformin. The primary end point was the change in HbA1c from baseline to week 24. Secondary end points included fasting plasma glucose (FPG) level, 2-h postprandial glucose (PPG) level, body weight, and proportion of pa...
Patient Preference and Adherence, 2014
Fixed-dose combination (FDC) products represent a widely accepted approach to type 2 diabetes treatment, given that monotherapies sometimes fail to meet the treatment targetsobtaining a sustained reduction in micro-and macrovascular complications. Saxagliptin (SAXA)/ metformin (MET) FDC tablets can be used either alone or in combination with glyburide, thiazolidinediones, or insulin. It has been proven that the SAXA/MET combination leads to a significant improvement in glycemic control compared to placebo in patients with type 2 diabetes that is inadequately controlled with MET alone. In addition, this FDC has been proven to be safe for people with diabetes mellitus and established cardiovascular disease, elderly patients, and patients with impaired renal function (.30 mL/minute), with dosage modification. Patient compliance, adherence, and persistence to the therapeutic regimen has been shown to be very good, while the titration of each compound according to the patient's profile is easy, given the availability of different formulations. The SAXA/MET FDC is a patient-friendly, dosage-flexible, and hypoglycemia-safe regimen with very few adverse events and a neutral or even favorable effect on body weight. It achieves significant glycosylated hemoglobin A 1c reduction helping the patient to achieve his/her individual glycemic goals.
2019
Current word count-250 words Background: We assessed the effects of the SGLT2 inhibitor dapagliflozin alone and in combination with the DPP4 inhibitor saxagliptin on albuminuria and HbA1c in patients with type 2 diabetes and chronic kidney disease in a double-blind placebo-controlled multicentre multinational study (DELIGHT study; clinicaltrials.gov, NCT02547935). Methods: After a 4-week single-blind placebo lead-in period, 448 participants were randomised (1:1:1; using computer-generated codes) to dapagliflozin 10 mg (n=145), dapagliflozin 10 mg and saxagliptin 2.5 mg (n=155) or placebo (n=148) once daily for 24 weeks. Inclusion criteria included urinary albumin-to-creatinine ratio (UACR) 30-3500 mg/g, eGFR 25-75 mL/min/1•73 m 2 , HbA1c 7-11% (53-97 mmol/mol) and stable doses of ACEi/ARB and glucose lowering treatment for ≥12 weeks. Primary endpoints were change from baseline in UACR (dapagliflozin and dapagliflozin/saxagliptin) and HbA1C (dapagliflozin/saxagliptin) at Week 24. Findings: Dapagliflozin and dapagliflozin/saxagliptin significantly reduced UACR versus placebo. This effect was sustained over the study period; at Week 24, change in UACR was −21•0% (95% CI, −34•1, −5•2; p=0•011) for dapagliflozin (n=132) and −38•0% (−48•2, −25•8; p<0•001) for dapagliflozin/saxagliptin (n=139) compared with placebo (n=134). HbA1c was reduced with dapagliflozin/saxagliptin (n=137) compared with placebo (n=118) (Week 24; −0•58% [−0•80 to −0•37; p<0•001]). The proportion of patients with adverse events (79/145 [54•5%], 104/152 [68•4%] and 81/148 [54•7%]) or serious adverse events (12/145 [8•3%], 12/152 [7•9%] and 16/148 [10•8%]) was similar across groups. There were no new drug-related safety signals. Interpretation: Dapagliflozin alone and dapagliflozin/saxagliptin conferred significant improvements in albuminuria in these patients; dapagliflozin/saxagliptin conferred a clinically significant reduction in both albuminuria and HbA1c at Week 24.
BMC Endocrine Disorders, 2014
Background: To compare the safety and efficacy of saxagliptin 2.5 mg twice daily (BID) versus placebo add-on therapy to metformin immediate release (IR) in patients with type 2 diabetes and inadequate glycemic control with metformin alone. Methods: This multicenter, 12-week, double-blind, parallel-group trial enrolled adult outpatients with type 2 diabetes (glycated hemoglobin [HbA 1c ] 7.0%-10.0%) on stable metformin IR monotherapy (≥1500 mg, BID for ≥8 weeks). Patients were randomized to double-blind saxagliptin 2.5 mg BID or placebo added on to metformin IR following a 2-week, single-blind, placebo add-on therapy lead-in period. The primary end point was the change from baseline to week 12 in HbA 1c . Key secondary end points included change from baseline to week 12 in fasting plasma glucose (FPG) and the proportion of patients achieving HbA 1c <7.0% or HbA 1c ≤ 6.5% at week 12. Efficacy was analyzed in all patients who received randomized study drug with ≥1 postbaseline assessment. Safety was assessed in all treated patients.
Diabetic Medicine, 2014
Aims To assess initial pharmacotherapy of Type 2 diabetes with the sodium-glucose cotransporter-2 inhibitor dapagliflozin. Methods This double-blind, placebo-controlled trial, randomly allocated people with Type 2 diabetes aged 18-77 years and inadequate glycaemic control on diet and exercise [HbA 1c 53-86 mmol/mol (7.0-10.0%)] to receive placebo (n = 75) or dapagliflozin monotherapy 2.5 mg (n = 65), 5 mg (n = 64) or 10 mg (n = 70) once daily in the morning. After 24 weeks, low-dose double-blind metformin 500 mg/day was added to the placebo group regimen (placebo+low-dose metformin group). Changes in HbA 1c level, fasting plasma glucose and body weight, as well as adverse events, were assessed over 102 weeks. Results Of the 274 participants randomized, 167 completed the study (60.9%). At 102 weeks, significant differences vs placebo+low-dose metformin with dapagliflozin 5 and 10 mg were observed for HbA 1c (À5.8 mmol/mol [À0.53%], P = 0.018; and À4.8 mmol/mol [À0.44%], P = 0.048), respectively); and for FPG (À0.69 mmol/L, P = 0.044; and À1.12 mmol/l, P = 0.001, respectively). For body weight, the difference between the dapagliflozin 10-mg group and the placebo+low-dose metformin group was significant (À2.60 kg; P = 0.016). Hypoglycaemic events were uncommon, with rates of 5.3% for placebo+low-dose metformin group and 0-4.6% for the dapagliflozin groups. Genital infections and urinary tract infections were more common in the dapagliflozin groups than in the placebo+low-dose metformin group. Conclusions Dapagliflozin as monotherapy in treatment-na€ ıve people with early Type 2 diabetes improved glycaemic control and reduced weight without increasing hypoglycaemia over 102 weeks. Dapagliflozin may provide an alternative initial pharmacotherapy in such people.
Diabetology & Metabolic Syndrome, 2010
Saxagliptin is a potent, selective DPP4 inhibitor. Highlights from abstracts presented at the 2010 meetings of the European Association for the Study of Diabetes and the American Diabetes Association include studies and analyses that shed light on the promising role for saxagliptin within the management of type 2 diabetes mellitus. Data show that saxagliptin combination therapy improves HbA 1c levels compared with placebo, particularly in patients with high HbA 1c at baseline, long duration of disease, low baseline creatinine clearance, and low homeostasis model assessment 2 β-cell function at baseline. These efficacy benefits are achieved without any increase in hypoglycemia or other adverse events. The study results also show that the saxagliptin plus metformin combination is a good candidate for initial therapy in drug-naïve patients treated for as long as 72 weeks. Survey data presented confirm that hypoglycemia (and fear of hypoglycemia) is a barrier to patients' acceptance of diabetes treatment, limiting its efficacy. Therefore, therapies such as saxagliptin that have a low risk of hypoglycemia may be more acceptable to patients in helping them to achieve glycemic control and to optimize their quality of life. In patients with renal impairment, for whom metformin is contraindicated, saxagliptin monotherapy is a promising option for antidiabetic management as, when given at a reduced dose, it is well-tolerated with a safety profile similar to that of placebo.
The Lancet Diabetes & Endocrinology, 2019
Current word count-250 words Background: We assessed the effects of the SGLT2 inhibitor dapagliflozin alone and in combination with the DPP4 inhibitor saxagliptin on albuminuria and HbA1c in patients with type 2 diabetes and chronic kidney disease in a double-blind placebo-controlled multicentre multinational study (DELIGHT study; clinicaltrials.gov, NCT02547935). Methods: After a 4-week single-blind placebo lead-in period, 448 participants were randomised (1:1:1; using computer-generated codes) to dapagliflozin 10 mg (n=145), dapagliflozin 10 mg and saxagliptin 2.5 mg (n=155) or placebo (n=148) once daily for 24 weeks. Inclusion criteria included urinary albumin-to-creatinine ratio (UACR) 30-3500 mg/g, eGFR 25-75 mL/min/1•73 m 2 , HbA1c 7-11% (53-97 mmol/mol) and stable doses of ACEi/ARB and glucose lowering treatment for ≥12 weeks. Primary endpoints were change from baseline in UACR (dapagliflozin and dapagliflozin/saxagliptin) and HbA1C (dapagliflozin/saxagliptin) at Week 24. Findings: Dapagliflozin and dapagliflozin/saxagliptin significantly reduced UACR versus placebo. This effect was sustained over the study period; at Week 24, change in UACR was −21•0% (95% CI, −34•1, −5•2; p=0•011) for dapagliflozin (n=132) and −38•0% (−48•2, −25•8; p<0•001) for dapagliflozin/saxagliptin (n=139) compared with placebo (n=134). HbA1c was reduced with dapagliflozin/saxagliptin (n=137) compared with placebo (n=118) (Week 24; −0•58% [−0•80 to −0•37; p<0•001]). The proportion of patients with adverse events (79/145 [54•5%], 104/152 [68•4%] and 81/148 [54•7%]) or serious adverse events (12/145 [8•3%], 12/152 [7•9%] and 16/148 [10•8%]) was similar across groups. There were no new drug-related safety signals. Interpretation: Dapagliflozin alone and dapagliflozin/saxagliptin conferred significant improvements in albuminuria in these patients; dapagliflozin/saxagliptin conferred a clinically significant reduction in both albuminuria and HbA1c at Week 24.
Drugs - Real World Outcomes, 2023
Background Real-world Indian studies evaluating effectiveness of dapagliflozin as an add-on to other oral antidiabetic drugs (OAD) in patients with type 2 diabetes mellitus (DM) are scarce. Methods An electronic medical record (EMR)-based, retrospective, multicentre study was conducted to evaluate the effectiveness of dapagliflozin as add-on therapy in adult patients with inadequately controlled DM on metformin with or without other OAD. Baseline characteristics (visit 1: metformin or metformin plus OAD treatment for at least 30 days) and treatmentrelated outcomes (visit 2: follow-up) considered between 60 and 140 days after adding/switching dapagliflozin [glycated haemoglobin (HbA1c), body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP)] were analysed. Results A total of 3616 patients were screened from 478 centres. Most patients had received dapagliflozin (D) + metformin (M) + at least one other OAD [D + M + OAD, n = 2907 (80.4%), 408 followed-up with HbA1c reported], while 709 patients (19.6%, 138 followed-up with HbA1c reported) received dapagliflozin + metformin (D + M). Treatment with dapagliflozin as an add-on therapy resulted in significant change in HbA1c (−1.1 ± 1.44%; p < 0.05 for HbA1c subgroup ≥ 7.5%; −1.6 ± 1.41%; p < 0.05 for HbA1c subgroup ≥ 8%) at visit 2 compared with visit 1. Significant change in body weight (−1.4 ± 3.31 kg; p < 0.05 for HbA1c subgroup ≥ 7.5%; − 1.5 ± 3.22 kg; p < 0.05 for HbA1c subgroup ≥ 8%) was observed at visit 2. Similarly, a significant change in BMI was noted for the HbA1c subgroup ≥ 7.5% (−1.0 ± 8.38 kg/m 2). However, the change in BMI in the HbA1c subgroup ≥ 8% was noted to be −1.4 ± 10.4 kg/m 2 , which was not statistically significant (p = 0.08). In the overall study population, significant change in the SBP (−4.5 ± 14.9 mmHg; p < 0.05 for HbA1c subgroup ≥ 7.5%; −4.5 ± 15.1 mmHg; p < 0.0001 for HbA1c subgroup ≥ 8%) was observed at visit 2 compared with visit 1. On identical lines, significant change in DBP (−1.5 ± 8.94 mmHg; p < 0.05 for HbA1c subgroup ≥ 7.5%; −1.4 ± 8.91 mmHg; p < 0.05 for HbA1c subgroup ≥ 8%) was noted. Conclusions Dapagliflozin showed significant improvement in glycemic parameter, BMI and BP when added to metformin, with or without other OADs in a real-world scenario.
Diabetes is a complex and chronic illness characterized by hyperglycemia. Anti-diabetic agents become less effective overtime and are often associated with undesirable effects. Improvement in glycemic control through inhibition of sodium glucose co-transporter (SGLT-2) inhibitors is an attractive, insulin independent target for increasing glucose excretion via urine, resulting in reduction of glycated hemoglobin, fasting and postprandial plasma glucose in patients with Type 2 Diabetes Mellitus (T2DM). SGLT2 inhibitor dapagliflozin provides an alternative and an addition to existing therapies for the treatment of patients with T2DM. It is a stable, competitive, reversible and highly selective inhibitor of SGLT-2 with an insulin-independent mechanism of action. It has potential to reduce hyperglycemia by inhibiting glucose reabsorption in kidney. Dapagliflozin when used as monotherapy and as add-on with metformin, glimepiride, sitagliptin or insulin improved glycemic control and resulted in statistically significant (p<0.0001) reductions in HbA 1c compared to placebo. In clinical trials incidence of adverse events after single and multiple doses of dapagliflozin did not appear to be dose-related. Multiple oral doses of dapagliflozin either alone or with metformin were found to be safe and well tolerated. In randomized controlled trials hyperglycemia occurred in similar proportion of patients in dapagliflozin and placebo group. Urinary tract and genital infections were reported more in dapagliflozin treated patients than placebo. Dapagliflozin was not associated with an increase in cardiovascular risk in T2DM patients. Dapagliflozin with its unique and complimentary action either alone or in combination with other antidiabetic drugs provide an important option for the management of T2DM.