saxagliptin/metformin XR / Generic mfg. - LARVOL DELTA

Comparison chart: SGLT2 inhibitors. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal

Effectiveness of triple therapy with dapagliflozin add-on to dual therapy over 52 weeks in patients with uncontrolled type 2 diabetes mellitus in a centre of high complexity, Cali-Colombia. (PubMed, Arch Endocrinol Metab) - "A historical cohort study was conducted in 123 adult patients over 18 years old who were diagnosed with uncontrolled T2DM, who received dapagliflozin add-on to their dual base treatment: metformin plus glibenclamide (n = 32), metformin plus saxagliptin (n = 29), metformin plus exenatide (n = 28), or metformin plus insulin (n = 34)...The proportion of patients achieving HbA target (<7%) was highest in the group that used a dapagliflozin add-on to metformin plus saxagliptin. The addition of dapagliflozin as an alternative for intensification of dual therapy consistently improved, not only FPG and HbA, but also body weight and blood pressure, with statistically significant results."

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

[VIRTUAL] Incidence of diabetic patients with ASCVD or Heart Failure on DPP4s and candidates for GLP-1 agonists or SGLT-2s for improved cardiovascular outcomes and reduced cost (ASHP 2020) - " Retrospective EMR Review (EPIC) Population: Patients with Type 2 Diabetes Mellitus with additional comorbidities of ASCVD or HF currently on therapy of DPP4 inhibitor Inclusion Criteria: Patients ≥ 18 years of age Patients with uncontrolled Type 2 Diabetes Mellitus + ASCVD or HF Patients on therapy of DPP4 Inhibitor Exclusion Criteria (based on chart review): Pregnancy Previous Failure of GLP-1 in patients with ASCVD Previous Failure of SGLT-2 inhibitors in patients with heart failure Patients on hemodialysis or continuous renal replacement therapy (CRRT) Patients with eGFR < 30 mL/min in patients with heart failure Patients with significant history of urinary tract infections (3+/year) in patients with heart failure History of pancreatitis in patients with ASCVD History of medullary thyroid carcinoma (MTC) in patients with ASCVD Patients with multiple endocrine neoplasia syndrome type 2 (MEN2) in patients with ASCVD Data Collection: Patient Demographics: Sex Age..."

Clinical • Allergy • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Immunology • Infectious Disease • Metabolic Disorders • Nephrology • Oncology • Pancreatitis • Renal Disease • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • Type 2 Diabetes Mellitus

Safety and Efficacy of Dapagliflozin in Asian T2DM Subjects With Inadequate Glycemic Control on Metformin/Saxagliptin (clinicaltrials.gov) - P3; N=41; Terminated; Sponsor: AstraZeneca; N=342 ➔ 41; Trial completion date: Nov 2021 ➔ Aug 2020; Suspended ➔ Terminated; Trial primary completion date: Nov 2021 ➔ Aug 2020; Sponsor decided to stop commercialization of QTERNMet/Qtrilmet and to stop all related ongoing activities/studies for business reasons.

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and safety of dapagliflozin plus saxagliptin vs monotherapy as added to metformin in patients with type 2 diabetes: A meta-analysis. (PubMed, Medicine (Baltimore)) - "Patients taking the DSM therapy had better effects in reducing the level of HbA1c, FPG, body weight, SBP and DBP than the DM and SM therapy. However, patients treated with DSM therapy are more likely to have hypoglycemia and genital infection. Dapagliflozin plus saxagliptin may be a suitable therapy strategy for patients with T2DM inadequately controlled with metformin, and this will provide a clinical reference for the treatment of T2DM."

Journal • Monotherapy • Retrospective data • Diabetes • Hypoglycemia • Infectious Disease • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

From Prediabetes to Type 2 Diabetes Mellitus in Women with Polycystic Ovary Syndrome: Lifestyle and Pharmacological Management. (PubMed, Int J Endocrinol) - "Metformin and pioglitazone treatments showed similar effects on fasting glucose levels. The sodium-glucose cotransporter-2 inhibitor empagliflozin did not show differences in metabolic parameters when compared to metformin...Likewise, a combination therapy with the dipeptidyl peptidase-4 inhibitor saxagliptin and metformin demonstrated superiority versus metformin in fasting glucose and oral glucose tolerance test normalization. Myo-inositol supplementation was associated with lower insulin levels, glucose levels, and insulin resistance when compared with placebo, metformin, or estrogen treatments. The use of insulin-sensitizing agents, such as metformin and inositols, along with lifestyle interventions may improve the metabolic profile in PCOS women."

Clinical • Journal • Review • Diabetes • Metabolic Disorders • Polycystic Ovary Syndrome • Type 2 Diabetes Mellitus

Cost-Utility Analysis of Saxagliptin/Dapagliflozin Versus Gliclazide and Insulin Glargine: Economic Implications of the Outcomes of the CVD-Real Studies I and II. (PubMed, Health Serv Insights) - "We calculated the total direct annual cost per patient of saxagliptin/dapagliflozin versus gliclazide and insulin glargine for patients with type 2 diabetes mellitus not achieving glycemic control on metformin plus saxagliptin alone, dapagliflozin alone, or gliclazide at a lower dosage. Then, saxagliptin/dapagliflozin can be considered a cost-effective oral hypoglycemic agent. The positive effect of this drug on the quality of life, induced by the bodyweight loss, has allowed this outcome, despite the higher annual cost per patient, mainly determined by the drug purchase cost."

HEOR • Journal • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

The Use of Saxagliptin in People with Type 2 Diabetes in France: The Diapazon Epidemiological Study. (PubMed, Diabetes Ther) - "Saxagliptin is efficacious and well tolerated in a real-world practice setting, with almost 80% of participants remaining on treatment after 2 years."

Journal • Biosimilar • Diabetes

Efficacy and Safety of Saxagliptin Added to Insulin With or Without Metformin in Chinese Patients with Type 2 Diabetes (ADA 2017) - P3b; "SAXA significantly improved glycemic control in Chinese patients with T2D and was well tolerated when added to insulin, with or without MET."

Clinical • Biosimilar • Diabetes • Immunology

Effects of vildagliptin versus saxagliptin on daily acute glucose fluctuations in Chinese patients with T2DM inadequately controlled with a combination of metformin and sulfonylurea. (PubMed) - "Vildagliptin produced a significantly greater reduction in acute glucose fluctuations compared with saxagliptin when added to a dual combination of metformin and sulfonylurea in Chinese patients with T2DM. Chinese Clinical Trial Registration Number: ChiCTR-TRC-13003858."

Journal • Biosimilar • Diabetes

Bioequivalence of saxagliptin/metformin immediate release (IR) fixed-dose combination tablets and single-component saxagliptin and metformin IR tablets in healthy adult subjects (Clin Drug Investig) - PMID: 23549864; P1, N=24; NCT00899470, NCT00897390; Sponsor: BMS: "...saxagliptin and metformin in the FDCs were bioequivalent to the individual components in both the fed and the fasted states as the limits of the 90 % confidence interval of the ratio of adjusted geometric means for all key pharmacokinetic parameters were contained within the predefined 0.800 to 1.250 bioequivalence criteria."

P1 data • Diabetes

AstraZeneca completes the acquisition of Bristol-Myers Squibb share of global diabetes alliance (AstraZeneca Press Release) - "AstraZeneca today announced that it completed, on 1 February 2014, the acquisition of the entirety of Bristol-Myers Squibb’s interests in the companies’ diabetes alliance...the acquisition gives AstraZeneca ownership of the intellectual property and global rights for the development, manufacture and commercialisation of the diabetes business, which includes Onglyza® (saxagliptin), Kombiglyze™ XR (saxagliptin and metformin HCl extended release), Komboglyze™ (saxagliptin and metformin HCl), dapagliflozin (marketed as Forxiga® outside the US and Farxiga® in the US), Xigduo™ (dapagliflozin and metformin HCl), Byetta® (exenatide), Bydureon® (exenatide extended-release for injectable suspension), metreleptin and Symlin® (pramlintide acetate)."

Licensing / partnership • Diabetes • Obesity

KOMBOGLYZE receives marketing authorisation in the European Union for adult patients with type 2 diabetes (AstraZeneca) - European Commission has granted marketing authorisation for KOMBOGLYZE (saxagliptin and metformin HCl immediate-release fixed dose combination) that will cover the 27 Member States of the European Union; The approval of KOMBOGLYZE is based on a saxagliptin development programme that involved 4,326 pts, including 2,158 individuals receiving saxagliptin plus metformin

EU approval • Diabetes

Komboglyze now authorised in Ireland for type 2 diabetes (Irish Medical Times) - "...the fixed dose combination Komboglyze is now available in Ireland for the treatment of adult patients with type 2 diabetes."

Launch • Diabetes

Metformin and saxagliptin combination treatment reduces nitroxidative stress and restores nitric oxide release in the endothelium of obese rats (ADA 2012) - Presentation time: 6/10/2012 3:00:00 PM; Saxagliptin was found to increase aortic and glomerular endothelial NO release by 20% (299 ± 57 nM to 360 ± 29 nM) and 21% (110 ± 14 nM to 133 ± 24 nM), respectively, while decreasing ONOO- release by 11% and 16%, respectively, as compared to vehicle-treated controls

Preclinical-animal • Diabetes

Treatment of type 2 diabetes with saxagliptin: A pharmacoeconomic evaluation in Argentina - PMID: 23621944; “...total cost of the SAXA + MET cohort was 15% higher than that of the SU + MET cohort. Treatment with SAXA + MET resulted in a higher number of quality-adjusted life years (QALYs) (9.54 vs. 9.32) and life-years gained (LYGs) (20.84 vs. 20.76) compared to those treated with SU + MET”

Pricing • Diabetes

Germany's IQWiG finds no added benefit for Komboglyze or for Pixuvri (The Pharma Letter) - "In an early benefit assessment...the Institute for Quality and Efficiency in Health Care (IQWiG) has examined whether the fixed combination of the drugs saxagliptin and metformin...offers an added benefit versus the current standard treatment for diabetes...Such an added benefit cannot be derived from the dossier for Komboglyze, however, as the manufacturer did not submit any relevant data..."

Reimbursement • Diabetes

Saxagliptin versus glipizide as add-on therapy to metformin: Assessment of hypoglycemia (Curr Med Res Opin) - P3, N=891; NCT00575588; Sponsor: AstraZeneca; "The mean (SD) number of hypoglycemic events per patient reporting hypoglycemia was lower with saxagliptin + metformin versus glipizide + metformin through weeks 52 (1.5 [SD 0.88] vs 4.8 [SD 4.9], respectively) and 104 (1.6 [SD 0.99] vs 5.4 [SD 5.8])...Saxagliptin + metformin was associated with fewer patients reporting hypoglycemia and fewer and less severe hypoglycemic events in those experiencing hypoglycemia compared with glipizide + metformin."

P3 data • Diabetes

Investor Presentation (AstraZeneca) - Anticipated launch in EU for type 2 diabetes in early 2013

Anticipated launch Europe • Diabetes

A randomized controlled trial of the efficacy and safety of twice-daily saxagliptin plus metformin combination therapy in patients with type 2 diabetes and inadequate glycemic control on metformin monotherapy (BMC Endocr Disord) - P3, N=166; NCT00885378;  Sponsor: Bristol Myers Squibb; "At week 12, least-squares mean changes (95% CI) from baseline HbA1c (adjusted for baseline HbA1c) were significantly greater (P = 0.006) in the saxagliptin + metformin group -0.56% (-0.74% to -0.38%) versus the placebo + metformin group -0.22% (-0.39% to -0.06%)...There were no unexpected safety findings."

P3 data • Diabetes

AstraZeneca: Annual Report 2013 (AstraZeneca) - Anticipated composition of matter patent expiry in US in 2023; Anticipated composition of matter patent expiry in EU in 2026

Anticipated patent expiry • Diabetes

Frequency of hypoglycemia: Patients receiving saxagliptin plus metformin vs. sulfonylurea (SU) plus metformin in real-world clinical practice (ENDO 2012) - N=1,567 (saxagliptin ) and 21,025 (SU) pts; The rate of hypoglycemia in the saxagliptin cohort was 1.74 per 100 PY vs. 6.68 in the SU cohort (rate ratio 0.31, 0.14 – 0.60) and 4.45 per 100 PY in the matched SU pts (rate ratio 0.39, 0.17 – 0.77); After multivariate adjustment, the rate ratio was 0.37, (0.19 – 0.74)

Retrospective data • Diabetes

Clinical Review: Safety and Efficacy comparison between Sulfonylureas and Dipeptidyl Peptidase-4 Inhibitors as Second-Line Therapies in Type 2 Diabetes Mellitus. (PubMed, Curr Pharm Des) - "Despite the higher efficacious characteristics of sulfonylureas in lowering HbA1c, due to its reported hypoglycemic effects, DPP-4 inhibitors may be considered as a clinically stable choice for second-line therapy after completing maximally tolerated doses of metformin. Sulfonylureas is considered better than DPP4 inhibitors for treatment in patients with cardiovascular disease history and low of hypoglycemia."

Clinical • Journal • Review

A 37-Year-Old Man With Pleuritic Chest Pain. (PubMed, Chest) - "Two weeks earlier, he had been evaluated at an urgent care for cough and was prescribed a 5-day course of azithromycin for bronchitis...His medications included atorvastatin, lisinopril, metformin, and saxagliptin. His parents were from Guam, although he was born and raised in San Diego, CA. He was employed as a social worker and denied any history of cigarette smoking, alcohol, or drug use."

Journal

Safety and Efficacy of Dapagliflozin in Asian T2DM Subjects With Inadequate Glycemic Control on Metformin/Saxagliptin (clinicaltrials.gov) - P3; N=342; Suspended; Sponsor: AstraZeneca; Recruiting ➔ Suspended

Clinical • Trial suspension