Qtern (dapagliflozin/saxagliptin) / AstraZeneca - LARVOL DELTA

Safety and efficacy of fixed-dose combination of dapagliflozin and saxagliptin in patients with type 2 diabetes mellitus - a phase 4 study in India. (PubMed, Front Endocrinol (Lausanne)) - "The mean absolute change in HbA1c (1.2% ± 1.1%), FPG (24.4 ± 62.9 mg/dL), and weight (2.1 ± 4.0 kg) from baseline to 24 weeks was statistically significant (p < 0.0001). Our study demonstrated the safety and efficacy of once-daily FDC of dapagliflozin and saxagliptin when added to metformin in Indian patients with T2DM."

Clinical • Journal • P4 data • Cardiovascular • Diabetes • Hypertension • Hypoglycemia • Infectious Disease • Metabolic Disorders • Nephrology • Type 2 Diabetes Mellitus

Cardio-renal effect of dapagliflozin and dapagliflozin- saxagliptin combination on CD34 + ve hematopoietic stem cells (HSCs) and podocyte specific markers in type 2 diabetes (T2DM) subjects: a randomized trial. (PubMed, Stem Cell Res Ther) - P4 | "Several parameters showed significant improvement with both Dapa alone and Combo compared to placebo. However, when all outcome measures were taken into account, other than glycemic control the Combo didn't seem to offer any further benefit, over Dapa alone. Therefore, contrary to our initial hypothesis we do not believe the more expensive Dapa + Saxa combination offers any specific cardiovascular benefit compared to Dapagliflozin alone. However it is noteworthy that both Dapa and its combination with Saxagliptin showed significant improvement compared to placebo in T2DM, particularly when progenitor cell based numbers and function were analyzed and taken into account."

Biomarker • Clinical • Journal • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • CD34 • CRP • IL6 • LEP

Antidiabetic Medicines Consumption and Cost for Payer and Patients During Pandemia: The Case for Bulgaria (ISPOR-EU 2024) - "Two new INNs were included in the Positive Drug List (PDL) Saxagliptin/ Dapagliflozin and Semaglutide. The highest public spending was for Gliclazide (3.6 to 3.9 mil Euro), Metformin (2.9 to 2.8 mil Euro), and Empagliflozin/ Metformin (3.3 to 4.7 mil Euro)... Patients and society experienced heavy cost burden for type II diabetes medicines therapy during pandemic period and almost share expenditures proportionally. Policy measures for regular supply and decreasing co-payment are needed to avoid high cost burden for patients."

Clinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Dapagliflozin or saxagliptin in pediatric type 2 diabetes: a plain language summary. (PubMed, Curr Med Res Opin) - No abstract available

Journal • Diabetes • Metabolic Disorders • Pediatrics • Type 2 Diabetes Mellitus

Safety, Growth and Development After Dapagliflozin or Saxagliptin in Children With Type 2 Diabetes (T2NOW Follow-Up). (PubMed, J Clin Endocrinol Metab) - "Prior treatment with dapagliflozin or saxagliptin for 52 weeks did not raise any safety concerns relating to height, weight, BMI, Tanner staging, growth and maturation markers, bone biomarkers or AEs for up to 52 weeks following treatment discontinuation, in pediatric patients with T2D."

Clinical • Journal • Diabetes • Metabolic Disorders • Pediatrics • Type 2 Diabetes Mellitus

Long-term safety of dapagliflozin or saxagliptin in paediatric patients with type 2 diabetes: 104-week follow-up of the phase 3 T2NOW trial (EASD 2024) - P3 | "Pts received dapagliflozin 5 mg or 10 mg, saxagliptin 2.5 mg or 5 mg or placebo as add-on to diet, exercise, metformin and/or insulin for a 52-week (wk) double-blind period, followed by a 52-wk follow-up without study treatment. No safety concerns on growth, maturation or bone health were raised during the 52 wks of non-treatment follow-up in paediatric pts with T2D, following dapagliflozin or saxagliptin for up to 52 wks."

Clinical • P3 data • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus • IGFBP3

Efficacy and tolerability of initial triple combination therapy with metformin, dapagliflozin and saxagliptin compared with stepwise add-on therapy in drug-naïve patients with type 2 diabetes (TRIPLE-AXEL study): A multicentre, randomized, 104-week, open-label, active-controlled trial. (PubMed, Diabetes Obes Metab) - "Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients."

Combination therapy • Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

β-Cell Function, Incretin Effect, and Glucose Kinetics in Response to a Mixed Meal in Patients With Type 2 Diabetes Treated With Dapagliflozin Plus Saxagliptin. (PubMed, Diabetes Care) - "SAXA+DAPA provided superior glycemic control compared with DAPA or SAXA, with improved β-cell function, insulin sensitivity, GLP-1 availability, and glucose clearance."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Continuous Glucose Monitoring Profiles and Health Outcomes after Dapagliflozin Plus Saxagliptin vs Insulin Glargine. (PubMed, J Clin Endocrinol Metab) - "DAPA+SAXA and INS were equally effective in reducing HbA1c at 24 weeks, but people with T2D treated with DAPA+SAXA achieved greater time in range, greater reductions in glycemic excursions and variability, less time with hypoglycemia, and improved patient-reported health outcomes."

Clinical • HEOR • Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Trials and Tribulations - The Challenges of Clinical Trials in Children. (PubMed, NEJM Evid) - "In this issue of NEJM Evidence, we see the results of a randomized clinical trial of dapagliflozin or saxagliptin in pediatric type 2 diabetes (T2D). In children and adolescents with T2D, dapagliflozin achieved significant improvements in glycemia in the trial.1 In June 2023, following another pivotal trial, the U.S. Food and Drug Administration (FDA) approved empagliflozin and the combination of empagliflozin and metformin as additions to diet and exercise to improve blood sugar control in children 10 years and older with T2D. Metformin, the only other oral therapy available for the treatment of children with T2D, was first approved for pediatric use in 2000."

Clinical • Journal • Diabetes • Metabolic Disorders • Pediatrics • Type 2 Diabetes Mellitus

Dapagliflozin or Saxagliptin in Pediatric Type 2 Diabetes. (PubMed, NEJM Evid) - "Dapagliflozin or Saxagliptin in Pediatric Type 2 DiabetesDapagliflozin (a sodium-glucose co-transporter-2 inhibitor) and saxagliptin (a dipeptidyl peptidase-4 inhibitor) have both been approved by the U.S. Food and Drug Administration for the treatment of type 2 diabetes in adults but not in children. In this randomized trial of 245 pediatric patients (10 to 17 years of age) with uncontrolled type 2 diabetes, dapagliflozin but not saxagliptin significantly reduced A1C compared with placebo."

Journal • Diabetes • Metabolic Disorders • Pediatrics • Type 2 Diabetes Mellitus

Saxagliptin/dapagliflozin is non-inferior to insulin glargine in terms of β-cell function in subjects with latent autoimmune diabetes in adults: A 12-month, randomized, comparator-controlled pilot study. (PubMed, Diabetes Obes Metab) - "Saxagliptin/dapagliflozin was non-inferior to glargine in terms of β-cell function in this 12-month, small, phase 2b study, enrolling people with LADA with still viable endogenous insulin production. Weight loss was greater with saxagliptin/dapagliflozin, with no differences in glycaemic control or hypoglycaemic risk."

Journal • Diabetes • Hypoglycemia • Immunology • Metabolic Disorders

QTERN (SAXAGLIPTIN/DAPAGLIFLOZIN FDC) Regulatory Post-Marketing Surveillance (clinicaltrials.gov) - P=N/A | N=679 | Active, not recruiting | Sponsor: AstraZeneca | Completed ➔ Active, not recruiting | Trial completion date: Dec 2022 ➔ Mar 2024 | Trial primary completion date: Dec 2022 ➔ Mar 2024

Enrollment closed • Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Effects of dapagliflozin and dapagliflozin-saxagliptin on erythropoiesis, iron and inflammation markers in patients with type 2 diabetes and chronic kidney disease: data from the DELIGHT trial. (PubMed, Cardiovasc Diabetol) - P2/3 | "Dapagliflozin increased hemoglobin and reduced ferritin and urinary markers of inflammation, suggesting potentially important effects on iron metabolism and inflammation."

Journal • Chronic Kidney Disease • Diabetes • Hematological Disorders • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • IL6

Impacts of the DPP-4 Inhibitor Saxagliptin and SGLT-2 Inhibitor Dapagliflozin on the Gonads of Diabetic Mice. (PubMed, Biomedicines) - "Several diabetes medications have demonstrated potential adverse effects on the male reproductive system; however, the effects of saxagliptin and dapagliflozin have not been sufficiently examined. In conclusion, our study presents preliminary evidence for the safety and efficacy of dapagliflozin in alleviating testicular abnormalities induced by diabetes, making it a promising candidate drug for patients with diabetes in their reproductive age. As saxagliptin may have negative effects on fertility, its prescription should be avoided in young male diabetic patients."

Journal • Preclinical • Diabetes • Metabolic Disorders

Efficacy of initial triple combination therapy with metformin, dapagliflozin and saxagliptin in drug-naïve patients with type 2 diabetes: a randomised controlled trial (EASD 2023) - P3 | "CST was started with metformin followed by glimepiride, and sitagliptin sequentially. Initial combination therapy with metformin, dapagliflozin and saxagliptin effectively lowered HbA1c with higher tolerability compared with conventional stepwise treatment in recent-onset T2D."

Clinical • Combination therapy • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Effect of Dapagliflozin and Saxagliptin Combination on CD34+ve Endothelial Progenitor Cells (EPCs) in Type 2 Diabetes Subjects (AHA 2022) - "Our study indicates that several parameters showed significant differences of Dapa and Combo when compared to placebo. However, other than glycemic control the Combo did not offer any further benefit over Dapa alone as far as inflammatory markers or stem cell number or migration properties were concerned."

Clinical • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • CD34 • CRP • IL6 • LEP

Early Pharmacological Intervention (EPIC) to Preserve Beta-Cell Function in Prediabetes (PreDM) (ADA 2023) - "Subjects then were randomized to metformin (MET), pioglitazone (PIO), saxagliptin (SAXA) or dapagliflozin (DAPA). Early drug intervention in prediabetes with pioglitazone preserves beta cell function and improves insulin sensitivity better than MET, SAXA, and DAPA."

Late-breaking abstract • Metabolic Disorders • Type 2 Diabetes Mellitus

Early Pharmacological Intervention (EPIC) to Preserve Beta-Cell Function in Prediabetes (PreDM) (ADA 2023) - "Subjects then were randomized to metformin (MET), pioglitazone (PIO), saxagliptin (SAXA) or dapagliflozin (DAPA). Early drug intervention in prediabetes with pioglitazone preserves beta cell function and improves insulin sensitivity better than MET, SAXA, and DAPA."

Late-breaking abstract • Metabolic Disorders • Type 2 Diabetes Mellitus

Cardiorenal Effect of Dapagliflozin and Dapagliflozin-Saxagliptin Combination on CD34+ve Hematopoietic Stem Cells (HSCs) and Podocyte Specific Markers in Type 2 Diabetes Subjects (ADA 2023) - "Several parameters showed significant improvement with both Dapa and Combo vs placebo. However, other than glycemic control Combo didn’t offer any further benefit over Dapa alone in terms of HSC and biochemistry. Moreover, the Combo may have deleterious effect on renal podocyte inflammation which needs to be examined in a larger study."

Biomarker • Clinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • CD34 • CRP • IL6 • LEP • PODXL

Efficacy and Tolerability of Initial Triple Combination Therapy with Metformin, Dapagliflozin, and Saxagliptin Compared with Conventional Stepwise Add-on Therapy in Drug-Naïve Patients with Type 2 Diabetes—A Randomized, 104-Week, Open-Label, Active-Controlled Trial (ADA 2023) - "CST was started with metformin followed by glimepiride, and sitagliptin sequentially. Initial combination therapy with metformin, dapagliflozin and saxagliptin effectively lowered HbA1c with higher tolerability compared with conventional stepwise treatment in recent-onset T2D."

Clinical • Combination therapy • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Cardio-renal Effect Of Dapagliflozin Alone Versus Dapagliflozin- Saxagliptin Combination In Type 2 Diabetes (t2dm) Subjects (VASCULAR DISCOVERY 2023) - "Several parameters showed significant improvement with both Dapa and Combo vs placebo. However, other than glycemic control the Combo didn’t offer any further benefit over Dapa alone in terms of HSC, biochemistry and podocyte markers. Of note, the combination may have deleterious effect on renal podocyte inflammation which needs to be examined in a larger study."

Clinical • Diabetes • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus • CD34 • CRP • IL6 • LEP • PODXL

To Assess Safety of Fixed Dose Combination of Dapagliflozin and Saxagliptin in Type 2 Diabetes Mellitus Patients (clinicaltrials.gov) - P4 | N=200 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

QTERN (SAXAGLIPTIN/DAPAGLIFLOZIN FDC) Regulatory Post-Marketing Surveillance (clinicaltrials.gov) - P=N/A | N=679 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

QTERN (SAXAGLIPTIN/DAPAGLIFLOZIN FDC) Regulatory Post-Marketing Surveillance (clinicaltrials.gov) - P=N/A | N=689 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus