Abstract
Background and Aims: A number of significant positive and negative signals emerged from the CANVAS Program and CREDENCE trial with the use of canagliflozin. These signals are confusing. A Likelihood of being Helped of Harmed (LHH) analysis was conducted to determine the risk, benefit ratio associated with canagliflozin use and address the signals as a continuum.
Materials and Methods: LHH was calculated from the number needed to treat (NNT) and number needed to harm (NNH) available from the absolute risk reductions reported with the outcomes of interest, in these two trials.
Results: In the CANVAS Program, LHH for major adverse cardiovascular events (MACE) points at a significant benefit with canagliflozin use in comparison to amputation (1.65), fractures (1.65) and euglycaemic diabetic ketoacidosis (euDKA) (16.67) risks. Only genital fungal infections were significant more in both sexes (0.21-M and 0.1-F) when LHH was matched against the positive outcomes. In contrast, the hHF benefits were outweighed by amputation (0.95) and fracture risks (0.95).
In CREDENCE trial, the LHH for Primary composite, Renal composite and MACE, all supported the benefits in comparison to any adverse events encountered in the trial.
The LHH from pooled data (CANVAS Program and CREDENCE trial) was in favour of all the benefits (hHF and renal composites) except for MACE matched against amputation (0.66).
Conclusion: The outcome benefits were in favour of canagliflozin in comparison to all reported adverse events, when hHF and renal composite were under consideration, in both the individual and pooled LHH analysis. However, the MACE benefits were overwhelmed by amputation risk in the pooled analysis.
Keywords: Type 2 diabetes, canagliflozin, NNT, NNH, LHH, MACE, amputation.
Call for Papers in Thematic Issues
Advancing Diabetic Wound Healing: Mechanisms and Interventions
In recent years, diabetic wounds have become a global health concern with the increase in the incidence of diabetes. Diabetic wounds are a kind of chronic and refractory ulcer. It is generally due to the microcirculatory disturbances and the reduced levels of endogenous growth factors. Delayed cutaneous wound healing is ...read more
Oxidative and inflammatory responses in the development of secondary diabetic complications
Diabetes, along with its associated secondary complications, represents a significant global health challenge, contributing significantly to morbidity and mortality. Unhealthy lifestyle habits, reduced physical activity, environmental pollutants, and stress are pivotal factors in the onset of diabetes, particularly type-2 diabetes. Poorly managed hyperglycemia can lead to various complications, including neuropathy, ...read more
Related Journals
Anti-Cancer Agents in Medicinal Chemistry
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Bioactive Compounds
Current Cancer Drug Targets
Combinatorial Chemistry & High Throughput Screening
Current Cancer Therapy Reviews
Current Drug Safety
Current Drug Targets
Current Drug Therapy
Current Enzyme Inhibition
Related Books
Drug Addiction Mechanisms in the Brain
Textbook of Advanced Dermatology: Pearls for Academia and Skin Clinics (Part 1)
The NLRP3 Inflammasome: An Attentive Arbiter of Inflammatory Response
Software and Programming Tools in Pharmaceutical Research
Morphea and Related Disorders
Objective Pharmaceutics: A Comprehensive Compilation of Questions and Answers for Pharmaceutics Exam Prep
Frontiers in Clinical Drug Research - CNS and Neurological Disorders
Stem Cells in Clinical Application and Productization
Marine Biopharmaceuticals: Scope and Prospects
Medicinal Chemistry of Drugs Affecting Cardiovascular and Endocrine Systems
23