licogliflozin (LIK066) / Novartis - LARVOL DELTA

Efficacy & safety of sodium-glucose cotransporter-2 inhibitors in polycystic ovary syndrome: A meta-analysis with trial sequential analysis. (PubMed, Indian J Med Res) - "Results Five RCTs with 'low' risk of bias, including 205 patients with PCOS, receiving SGLT2i (empagliflozin, licogliflozin, dapagliflozin, and canagliflozin alone and in combination with metformin) or control (placebo, metformin, or exenatide) were evaluated in the meta-analysis. Interpretation & conclusions The findings of this meta-analysis suggest that SGLT2i improves the hormonal and glycaemic indices in patients with PCOS. It can prove to be a safe alternative in patients not responding to or intolerant of standard pharmacological treatments."

Clinical • Journal • Retrospective data • Acne Vulgaris • Endocrine Disorders • Genetic Disorders • Infertility • Obesity • Polycystic Ovary Syndrome • Sexual Disorders • Women's Health

Evaluation of three mechanisms of action (SGLT2 inhibitors, GLP-1 receptor agonists, and sulfonylureas) in treating type 2 diabetes with heart failure: a systematic review and network meta-analysis of RCTs. (PubMed, Front Endocrinol (Lausanne)) - "A Bayesian network meta-analysis was utilized to integrate direct and indirect evidence, facilitating a comparative ranking of various SGLT2 inhibitors-canagliflozin (CANA), ipragliflozin (IPRA), empagliflozin (EMPA), remogliflozin (REMO), licogliflozin (LICO), and dapagliflozin (DAPA)-as well as one GLP-1 receptor agonist-semaglutide (SEMA)-and a sulfonylurea-glimepiride (GLIM)-with respect to their efficacy and safety profiles. Despite its moderate efficacy, GLIM remains a viable choice for certain patients due to its favorable safety profile and cost-effectiveness. Collectively, these findings provide essential evidence-based insights to guide individualized therapeutic strategies in type 2 diabetes complicated by heart failure."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Hypoglycemia • Infectious Disease • Metabolic Disorders • Nephrology • Obesity • Type 2 Diabetes Mellitus

Role of Sodium-Glucose Cotransporter-2 Inhibitors in Managing Polycystic Ovary Syndrome: A Systematic Review. (PubMed, touchREV Endocrinol) - "Canagliflozin, empagliflozin, dapagliflozin and licogliflozin were studied either as monotherapy or in combination with metformin or exenatide. Adverse effects with SGLT2i were mostly mild and included genital infections. SGLT2i, when used as monotherapy or combined with metformin or GLP1RA, are a promising therapy for improving metabolic and hormonal parameters in PCOS."

Journal • Review • Dyslipidemia • Infectious Disease • Metabolic Disorders • Obesity • Polycystic Ovary Syndrome • Women's Health

Effects of SGLT-2 inhibitors on clinical and biological hyperandrogenism and menstruation irregularities in patients with polycystic ovary syndrome: A systematic review of randomized trials. (PubMed, SAGE Open Med) - "Five randomized studies were included, evaluating canagliflozin, dapagliflozin, licogliflozin, or empagliflozin against metformin, exenatide, or placebo, with a total of 214 participants. Sodium-glucose transporter type 2 inhibitors appear to have a potential but variable impact on hormonal parameters in women with polycystic ovary syndrome. However, larger and longer-duration studies are needed to fully elucidate their long-term efficacy in addressing hyperandrogenism and improving overall outcomes in these patients."

Clinical • Journal • Review • Polycystic Ovary Syndrome

Recent Advances in Individualized Clinical Strategies for Polycystic Ovary Syndrome: Evidence From Clinical Trials and Emerging Pharmacotherapies. (PubMed, Clin Ther) - "This comprehensive approach underscores the importance of tailored treatments in optimizing clinical outcomes and quality of life for women with PCOS. The aim of this review is to highlight recent advancements in the treatment of PCOS through clinical trials and emerging pharmacotherapies, emphasizing the need for individualized and multifaceted treatment approaches."

Journal • Review • Endocrine Disorders • Polycystic Ovary Syndrome

A Systematic Review on Effect of Sodium-Glucose cotransporter-2 inhibitors on the metabolic and endocrinological profile of patients with Polycystic Ovarian Syndrome. (PubMed, Expert Opin Pharmacother) - "The aim of this systematic review was to assess the safety and efficacy profile of sodium-glucose cotransporter 2 (SGLT2) inhibitors (Canagliflozin, Dapagliflozin, Empagliflozin, and Licogliflozin) for the treatment of women suffering from PCOS. Overall, there was improvement in metabolic and endocrine profiles, suggesting a potentially beneficial impact of SGLT2 inhibitors in the management of PCOS. There is a requirement for large extensive clinical trials to demonstrate the efficacy of SGLT-2 inhibitors in PCOS patients."

Clinical • Journal • Review • Polycystic Ovary Syndrome

ELIVATE: Efficacy, Safety and Tolerability of the Combination of Tropifexor & Licogliflozin and Each Monotherapy, Compared With Placebo in Adult Patients With NASH and Liver Fibrosis. (clinicaltrials.gov) - P2 | N=234 | Terminated | Sponsor: Novartis Pharmaceuticals | Completed ➔ Terminated; The sponsor made a business decision to stop development of the trial drugs. The decision to stop the trial early was not because of any safety concerns.

Combination therapy • Monotherapy • Trial termination • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Steatohepatitis

ELIVATE: Efficacy, Safety and Tolerability of the Combination of Tropifexor & Licogliflozin and Each Monotherapy, Compared With Placebo in Adult Patients With NASH and Liver Fibrosis. (clinicaltrials.gov) - P2 | N=235 | Completed | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Completed | N=380 ➔ 235 | Trial completion date: Mar 2024 ➔ Oct 2022 | Trial primary completion date: Apr 2023 ➔ Oct 2022

Combination therapy • Enrollment change • Monotherapy • Trial completion • Trial completion date • Trial primary completion date • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Steatohepatitis

FAILURE OF SGLT-2 INHIBITOR IN THE CONTEXT OF NEW ILEAL CONDUIT FORMATION (ISN-WCN 2023) - "His anti-diabetics, metformin and empagliflozin, were kept on hold during the peri-operative period and were reinitiated on post-operative day 2. This scenario could be an indication to use dual novel SGLT1/2 inhibitors like sotagliflozin and licogliflozin. More clinical trials are needed to validate this hypothesis."

Bladder Cancer • Diabetes • Genito-urinary Cancer • Metabolic Disorders • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • Urothelial Cancer

Dose-dependent efficacy and safety of licogliflozin on obese adults: A systematic review and meta-analysis of randomized controlled trials. (PubMed, Diabetes Metab Syndr) - "We found that licogliflozin was safe and tolerable. It reduces body weight significantly. Moreover, it improves glycemic control and other cardiometabolic parameters."

Journal • Retrospective data • Review • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Pain • Type 2 Diabetes Mellitus

Cu Single Atom Nanozyme Based High-Efficiency Mild Photothermal Therapy through Cellular Metabolic Regulation. (PubMed, Angew Chem Int Ed Engl) - "In this work, Cu SAzyme presents extraordinary multienzyme activities to induce reactive oxygen species (ROS) storm formation, which can damage the existing HSPs in cancer cells. Through a two-pronged strategy of SGLT inhibitor and ROS storm, LIK066-loaded Cu SAzyme shows high efficiency for comprehensive removal of HSPs to realize mild PTT."

Journal • Oncology

"https://t.co/SC7XXHCSov - inhibition of both the SGLT 1 and 2 with licogliflozin — is tolerance is going to be an issue? Diarrhea in 77% at 150 mg vs. 43% placebo, which was mostly mild in severity. @NoureddinMD @AlkhouriNaim" (@rajVuppaLanchi)

Clinical

Licogliflozin for nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a study. (PubMed, Nat Med) - P2 | "Studies of longer duration and in combination with drugs that have different mechanisms of action are needed to validate these findings and to define a role of licogliflozin as a therapeutic option for NASH. ClinicalTrials.gov identifier: NCT03205150."

Clinical • Journal • P2a data • Fibrosis • Hepatology • Immunology • Non-alcoholic Steatohepatitis

ELIVATE: Efficacy, Safety and Tolerability of the Combination of Tropifexor & Licogliflozin and Each Monotherapy, Compared With Placebo in Adult Patients With NASH and Liver Fibrosis. (clinicaltrials.gov) - P2 | N=380 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: May 2023 ➔ Mar 2024

Combination therapy • Monotherapy • Trial completion date • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Steatohepatitis

Effects of Sodium/Glucose Cotransporter 2 (SGLT2) Inhibitors and Combined SGLT1/2 Inhibitors on Cardiovascular, Metabolic, Renal, and Safety Outcomes in Patients with Diabetes: A Network Meta-Analysis of 111 Randomized Controlled Trials. (PubMed, Am J Cardiovasc Drugs) - "In patients with T2DM, compared with pure SGLT2 inhibitors, combined SGLT1/2 inhibitors demonstrated a lower risk of myocardial infarction and of stroke, but were associated with a higher risk of diarrhea and severe hypoglycemia."

Journal • Retrospective data • Cardiovascular • Diabetes • Metabolic Disorders • Myocardial Infarction • Severe Hypoglycemia • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

SGLT inhibitors on weight and body mass: A meta-analysis of 116 randomized-controlled trials. (PubMed, Obesity (Silver Spring)) - "SGLT inhibitors demonstrated weight reduction benefits in this meta-analysis. Further studies are needed to clarify their role in weight management."

Journal • Retrospective data • Diabetes • Metabolic Disorders

Licogliflozin effective in PCOS treatment. (PubMed, Nat Rev Endocrinol) - No abstract available

Journal • Polycystic Ovary Syndrome

Licogliflozin versus placebo in women with polycystic ovary syndrome (PCOS): a randomised, double-blind, phase 2 trial. (PubMed, Diabetes Obes Metab) - "Dual inhibition of SGLT1/2 ameliorates hyperinsulinemia and -androgenemia in women with PCOS. Licogliflozin may represent a promising novel treatment option for PCOS."

Clinical • Journal • P2 data • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Polycystic Ovary Syndrome

Glucosuric, renal and hemodynamic effects of a dual inhibitor of SGLT1 and SGLT2, licogliflozin, in patients with chronic kidney disease: a randomized trial. (PubMed, Diabetes Obes Metab) - "Licogliflozin treatment results in significantly increased UGE and favorable changes in urinary electrolytes and hemodynamics in patients with varying degrees of CKD (eGFR≥45 mL/min/1.73 m )."

Clinical • Journal • Chronic Kidney Disease • Nephrology • Pain • Renal Disease

ELIVATE: Efficacy, Safety and Tolerability of the Combination of Tropifexor & Licogliflozin and Each Monotherapy, Compared With Placebo in Adult Patients With NASH and Liver Fibrosis. (clinicaltrials.gov) - P2; N=380; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial primary completion date: Mar 2022 ➔ Apr 2023

Clinical • Combination therapy • Monotherapy • Trial primary completion date • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Steatohepatitis • MRI

Pharmacokinetics, Metabolism, and Excretion of Licogliflozin, a Dual Inhibitor of SGLT1/2, in Rats, Dogs, and Humans. (PubMed, Xenobiotica) - "In humans, direct glucuronidation to M17 and M27 was the major pathway observed, accounting for ∼38% of the dose in excreta while oxidative metabolism also contributed to >29% of the dose in excreta. Oxidative pathways were predominant in animal species."

Journal • PK/PD data

ELIVATE: Efficacy, Safety and Tolerability of the Combination of Tropifexor & Licogliflozin and Each Monotherapy, Compared With Placebo in Adult Patients With NASH and Liver Fibrosis. (clinicaltrials.gov) - P2; N=380; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Apr 2022 ➔ May 2023

Clinical • Combination therapy • Monotherapy • Trial completion date • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Steatohepatitis

"https://t.co/FCdy5gVf4h #AASLD #TLMdX #Obesity #Diabetes #FattyLiver #NASH #NAFLD #dapagliflozin #saxagliptin @AstraZeneca #QTERN #licogliflozin #tropifexor @Novartis #lanifibranor #inventiva #elafibranor @genfit_pharma #obeticholicacid #OCA @InterceptPharma" (@HepDynamics)

Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity

[VIRTUAL] SAFETY AND DRUG-DRUG INTERACTION OF TROPIFEXOR IN COMBINATION WITH LICOGLIFLOZIN IN HEALTHY BUT OVERWEIGHT TO OBESE SUBJECTS IN SUPPORT OF A Ph2b COMBINATION STUDY ELIVATE (AASLD 2020) - "Study data support the doses selected for the ELIVATE study, a Ph2b trial to assess the efficacy (histology based- primary endpoint), safety and tolerability of TXR and LIK combination therapy compared to each as monotherapy in patients with NASH and stage 2 or 3 fibrosis."

Clinical • Combination therapy • P2b data • Addiction (Opioid and Alcohol) • Fibrosis • Hepatology • Immunology • Non-alcoholic Steatohepatitis • Obesity

[VIRTUAL] LIK066 (LICOGLIFLOZIN), AN SGLT1/2 INHIBITOR, IMPROVES MARKERS OF HEPATIC AND METABOLIC HEALTH IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE: FULL STUDY ANALYSIS OF A 12-WEEK, RANDOMIZED, PLACEBO-CONTROLLED, PHASE 2a STUDY (AASLD 2020) - "Licogliflozin was safe and tolerable. Twelve weeks of licogliflozin treatment leads to dose-dependent improvements in liver injury and metabolic biomarkers. Studies of longer duration and in combination with drugs that have different mechanisms of action will define the role of licogliflozin as a therapeutic option for NASH."

Clinical • P2a data • Addiction (Opioid and Alcohol) • Diabetes • Genetic Disorders • Hepatology • Liver Failure • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity • Type 2 Diabetes Mellitus