Obesity is currently considered a low-grade chronic inflammatory condition that has well-documented associations with heart disease, hypertension, diabetes mellitus, and metabolic syndrome. In addition to these conditions, there is growing evidence that the inflammatory cytokines produced in obesity may play contributory roles in other inflammatory phenomena. Notably, numerous studies over the last several decades have shed light on the genetic, mechanistic, and epidemiologic links between obesity and psoriasis, with implications for the treatment of these patients. This article reviews the current literature regarding the relationship of obesity and psoriasis, with exploration of their common mechanistic etiology and the necessary considerations in the management, both pharmacological and otherwise, of this patient population.
Aim
To examine clinical and safety outcomes associated with metformin use in patients with impaired renal function.
Materials and Methods
We searched PubMed and Embase databases from inception to August 2020, supplementing our search with a review of investigator files and reference lists of included studies. Any study reporting original data on metformin and patient‐centred outcomes in patients with impaired renal function, defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2, was included. Post hoc meta‐analysis was performed for the outcomes of mortality, cardiovascular events and acidosis.
Results
Nine small prospective studies enrolling patients with significantly impaired renal function identified only one case of clinically apparent lactic acidosis. Among 13 larger retrospective studies, seven examined the risk of mortality across patient subgroups; meta‐analysis showed reductions in overall mortality at an eGFR of 45 mL/min/1.73m2 or higher but not at an eGFR of less than 45 mL/min/1.73m2. Eight retrospective studies evaluated acidosis as an outcome; meta‐analysis showed no increase in risk of acidosis except at an eGFR of less than 30 mL/min/1.73m2, in which group the HR was 1.97 (95% CI 1.03–3.77).
Conclusions
The literature shows metformin to be associated with reduced mortality and no increased risk of acidosis at an eGFR of 45 mL/min/1.73m2 or higher. Metformin appears to be associated with fewer benefits and possible increases in the risk of acidosis at an eGFR of less than 30 mL/min/1.73m2. Consistent with US Food and Drug Administration guidelines, metformin should not be used at an eGFR less than 30 mL/min/1.73m2, and further research on its risk‐benefit profile at eGFR values approaching 30 mL/min/1.73m2 is warranted.
This randomized, double-blind, placebo-controlled, n-of-1 crossover study assessed whether metformin's side effects are reproducible in patients with a history of metformin intolerance. Participants completed up to four cycles of 2 weeks of metformin exposure and 2 weeks of placebo exposure. Participants completed surveys based on the Gastrointestinal Symptom Rating Scale and the Treatment Satisfaction Questionnaire for Medication. The primary hypotheses were that treatment satisfaction would be equal for placebo and metformin and that more than 30% of the study enrollees would be able to adhere to a higher dose of metformin 6 months after participation. Thirteen patients (all women, mean age 52.4 years) enrolled, three of whom were lost to follow-up or were non-adherent to study protocol. Metformin was associated with significantly lower global treatment satisfaction scores compared with placebo (39.58 vs. 53.75, P < .05) but participants could not distinguish metformin from placebo and did not report higher rates of gastrointestinal side effects on metformin. Two out of 10 participants adhered to a higher dose of metformin after trial completion. Metformin appears to have barriers to use beyond its classic gastrointestinal side effects.
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