Use of sodium-glucose cotransporter-2 inhibitors in France: Analysis of French nationwide health insurance database.

AIM: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have been commercialized in France for type 2 diabetes since April 2020 and later for heart and renal diseases. Given the recent developments in treating diabetes and the widening of SGLT-2i indications, we aimed to study changes in the use of glucose-lowering drugs in France and to characterize SGLT-2i new users. METHODS: We performed a nationwide utilization study using the French health insurance database. Trends in incidence and prevalence of glucose-lowering drug use were assessed by a repeated cross-sectional study in 2019 and 2021. A cohort study of incident SGLT-2i users was then conducted to describe patient characteristics and the strategy for treating diabetes. RESULTS: The prevalence of SGLT-2i use gradually reached 0.1% in the third quarter of 2021 and increased more significantly to 0.2% thereafter. SGLT-2i became the second most prescribed glucose-lowering drug class after metformin at the end of 2021 (0.1%). Among the cohort of 125 387 SGLT-2i new users (mean age 65.0 years; 60.1% of men), 87.6% presented a diabetic comorbidity. The patient profile changed over the study period with an increasing proportion of patients with cardiovascular (28.7% in 2020 vs. 40.2% in 2021) or renal (7.7% in 2020 vs. 11.8% in 2021) comorbidities at initiation. The main combinations used at SGLT-2i initiation were metformin (12.5%) and metformin plus dipeptidyl peptidase-4 inhibitors (8.1%). One-year probability of SGLT-2i persistence was estimated to be 55%. CONCLUSION: The expansion of indications for SGLT-2i and the broadening of the target population make it essential to assess the reasons for discontinuation and review their safety profile.

What place for intelligent automation and artificial intelligence to preserve and strengthen vigilance expertise in the face of increasing declarations?

In 2018, the "Ateliers de Giens" (Giens Workshops) devoted a workshop to artificial intelligence (AI) and led its experts to confirm the potential contribution and theoretical benefit of AI in clinical research, pharmacovigilance, and in improving the efficiency of care. The 2022 workshop is a continuation of this reflection on AI and intelligent automation (IA) by focusing on its contribution to pharmacovigilance and the applications and tasks could be optimized to preserve and strengthen medical and pharmacological expertise in pharmacovigilance. The evolution of pharmacovigilance work is characterized by many tasks with low added value, a growing volume of pharmacovigilance reporting of suspected side effects, and a scarcity of medical staff with expertise in clinical pharmacology and pharmacovigilance and human resources to support this growing need. Together, these parameters contribute to an embolization of the pharmacovigilance system at risk of missing its primary mission: to identify and characterize a risk or even a health alert on a drug. The participants of the workshop (representatives of the Regional Pharmacovigilance Centres (CRPV), the French National Agency for Safety of Medicinal Products (ANSM), patients, the pharmaceutical industry, or start-ups working in the development of AI in the field of medicine) shared their experiences, their pilot projects and their expectations on the expected potential, theoretical or proven, AI and IA. This work has made it possible to identify the needs and challenges that AI or IA represent, in the current or future modes of organization of pharmacovigilance activities. This approach led to the development of a SWOT matrix (strengths, weaknesses, opportunities, threats), a basis for reflection to identify critical points and consider four main recommendations: (1) preserve and develop business expertise in pharmacovigilance (including research and development in methods) with the integration of new technologies; (2) improve the quality of pharmacovigilance reports; (3) adapt technical and regulatory means; (4) implement a development strategy for AI and IA tools at the service of expertise.

Quinolone antibiotics and suicidal behavior: analysis of the World Health Organization's adverse drug reactions database and discussion of potential mechanisms.

RATIONALE: Several case-reports suggest that the use of quinolones may increase the risk of psychiatric adverse reactions such as suicidal behaviors. OBJECTIVES: The aim of this study is to investigate whether there is a safety signal for quinolone-related suicidal behaviors in a global adverse drug reactions database. METHODS: All antibiotic-related adverse reactions were extracted from VigiBase, the World Health Organization (WHO) global Individual Case Safety Report (ICSR) database. Disproportionality analyses were performed to investigate the association between reports of suicidal behavior and exposure to quinolones, in comparison with other antibiotics. RESULTS: From December 1970 through January 2015, we identified 992,097 antibiotic-related adverse reactions. Among them, 608 were quinolone-related suicidal behaviors including 97 cases of completed suicides. There was increased reporting of suicidal behavior (adjusted reporting odds ratios [ROR] 2.78, 95 % CI 2.51-3.08) with quinolones as compared to other antibiotics. Candidate mechanisms for quinolone-induced suicidal behaviors include GABAA antagonism, activation of NMDA receptors, decreased serotonin levels, oxidative stress, and altered microRNA expressions. CONCLUSIONS: We found a strong safety signal suggesting an increased risk of suicidal behaviors associated with quinolone use. Plausible psychopharmacological mechanisms could underlie this association. Further investigations are urgent to confirm and better understand these findings.