A safety and tolerability profile comparison between dipeptidyl peptidase-4 inhibitors and sulfonylureas in diabetic patients: A systematic review and meta-analysis.

BACKGROUND: The first treatment approach for type 2 diabetes mellitus is lifestyle change and metformin, but it is usually not sufficient. For some time, the anti-hyperglycemic classes of sulfonylureas and dipeptidyl peptidase-4 (DPP-4) inhibitors were considered second-line of treatment, since they show similar efficacy effect. However, the recent ADA-EASD consensus gives the preference to DPP-4 inhibitors compared to sulfonylureas, except if cost is a major problem. We performed a meta-analysis for safety and tolerability profile to comprehend which treatment has less adverse events. METHODS: PUBMED and EMBASE databases were searched from inception until July 2017 to retrieve RCT studies comparing DPP-4 inhibitors and sulfonylureas treatments in adult type 2 diabetes patients. There was no language restriction. We extracted and combined data from studies comparison that reported safety profile and weight change. A random effect, meta-analytic model was applied to all calculations. Cochrane collaboration tool was used to assess quality and bias of the included studies. Trial registered with PROSPERO (CRD42017075823). FINDINGS: Out of 1472 articles identified in our search and screened for eligibility, 36 studies comparing DPP-4 inhibitors and sulfonylureas were identified. DPP-4 inhibitors in combination with metformin had less overall adverse events (RR: 0·90; 95% CI, 0·86-0·94; p < 0·0001; I2 = 83%; 17 studies), cardiovascular events (RR: 0·54; 95% CI, 0·37-0·79; p = 0·002; I2 = 0%; 6 studies), hypoglycemia (RR: 0·17; 95% CI, 0·13-0·22; p < 0·00001; I2 = 76%; 17 studies) and severe hypoglycemic events (RR: 0·10; 95% CI, 0·05-0·19; p < 0·00001; I2 = 0%; 12 studies). The mean difference of the weight change was 1·92 kg in favor of DPP-4 inhibitors in combination with metformin in relation to sulfonylureas in combination with metformin. Monotherapy with DPP-4 inhibitors also had less rates of hypoglycemia (RR: 0·31; 95% CI, 0·24-0·41; p < 0·00001; I2 = 0%; 8 studies) and severe hypoglycemic events (RR: 0·26; 95% CI, 0·10-0·66; p = 0·004; I2 = 0%; 8 studies) and patients did not gain 1·19 kg. INTERPRETATION: These results suggest better safety profile for DPP-4 inhibitors than sulfonylureas for both comparisons, and it is more notable when the treatment regimen includes metformin. FUNDING: This study was funded by Takeda Pharmaceuticals, Brazil.

[Star fruit as a cause of acute kidney injury]. / Carambola como causa de lesão renal aguda.

The star fruit belongs to the family Oxalidacea, species Averrhoa carambola. It is rich in minerals, vitamin A, C, B complex vitamins and oxalic acid. Recent studies show that the toxicity of the fruit differs between the patients and may be explained by single biological responses, age, and the intake quantity of the neurotoxin in each fruit in addition to glomerular filtration rate given by each patient. Additionally, the nephrotoxicity caused by the fruit is dose-dependent and may lead to the deposition of crystals of calcium oxalate intratubular, as well as by direct injury to the renal tubular epithelium, leading to apoptosis of the same. We report the case of a patient who after ingestion of the juice and fresh fruit, developed acute renal failure requiring dialysis, evolving with favourable outcome and recovery of renal function.

Carambola como causa de lesão renal aguda / Star fruit as a cause of acute kidney injury

A carambola pertence à família das Oxalidáceas, espécie Averrhoa carambola. É rica em sais minerais, vitaminas A, C, complexo B e ácido oxálico. Estudos recentes demonstram que a toxicidade da fruta difere entre os indivíduos e pode ser explicada pelas respostas biológicas individuais como idade, quantidade da ingestão, neurotoxinas em cada tipo de fruta. Adicionalmente, a nefrotoxicidade causada pela fruta é dose dependente, podendo levar ao desenvolvimento de lesão renal aguda pela deposição de cristais de oxalato de cálcio intratubular, assim como por lesão direta das células epiteliais tubulares, levando à apoptose das mesmas. Relatamos o caso de uma paciente que, após a ingestão do suco da fruta e fruta in natura, desenvolveu lesão renal aguda, necessitando de terapia dialítica, evoluindo com desfecho favorável e recuperação da função renal.

The star fruit belongs to the family Oxalidacea, species Averrhoa carambola. It is rich in minerals, vitamin A, C, B complex vitamins and oxalic acid. Recent studies show that the toxicity of the fruit differs between the patients and may be explained by single biological responses, age, and the intake quantity of the neurotoxin in each fruit in addition to glomerular filtration rate given by each patient. Additionally, the nephrotoxicity caused by the fruit is dose-dependent and may lead to the deposition of crystals of calcium oxalate intratubular, as well as by direct injury to the renal tubular epithelium, leading to apoptosis of the same. We report the case of a patient who after ingestion of the juice and fresh fruit, developed acute renal failure requiring dialysis, evolving with favourable outcome and recovery of renal function.