RESUMO

The lowest dosage of empagliflozin (10 mg) showed similar benefits on glycated hemoglobin (HbA1c) level, body weight, blood pressure, and total and cardiovascular mortality in comparison with the highest available dose (25 mg) in the EMPAREG trial. These findings have not been clearly demonstrated for canagliflozin and dapagliflozin. The objective was to compare the effect of different doses of SGLT2 inhibitors commercially available in Brazil on HbA1c and body weight of patients with type 2 diabetes. MEDLINE, Cochrane and Embase databases were searched from inception until 11th October 2021 for randomized controlled trials of SGLT2 inhibitors in type 2 diabetes patients, lasting at least 12 weeks. HbA1c and body weight variations were described using standard mean difference. We performed direct and indirect meta-analysis, as well as a meta-regression with medication doses as covariates. Eighteen studies were included, comprising 16,095 patients. In the direct meta-analysis, SGLT2 inhibitors reduced HbA1c by 0.62% (95% CI -0.66 to -0.59) and body weight by 0.60 kg (95% CI -0.64 to -0.55). In the indirect meta-analysis, canagliflozin 300 mg ranked the highest regarding reductions in HbA1c and body weight. The remaining medications and dosages were clinically similar, despite some statistically significant differences among them. Canagliflozin 300 mg seems to be more potent in reducing HbA1c and body weight in patients with type 2 diabetes. The remaining SGLT2 inhibitors at different doses lead to similar effects for both outcomes. Whether these glycemic and weight effects are reflected in lower mortality and cardiovascular events is still uncertain and may be a topic for further studies.

Assuntos

RESUMO

ABSTRACT The lowest dosage of empagliflozin (10 mg) showed similar benefits on glycated hemoglobin (HbA1c) level, body weight, blood pressure, and total and cardiovascular mortality in comparison with the highest available dose (25 mg) in the EMPAREG trial. These findings have not been clearly demonstrated for canagliflozin and dapagliflozin. The objective was to compare the effect of different doses of SGLT2 inhibitors commercially available in Brazil on HbA1c and body weight of patients with type 2 diabetes. MEDLINE, Cochrane and Embase databases were searched from inception until 11th October 2021 for randomized controlled trials of SGLT2 inhibitors in type 2 diabetes patients, lasting at least 12 weeks. HbA1c and body weight variations were described using standard mean difference. We performed direct and indirect meta-analysis, as well as a meta-regression with medication doses as covariates. Eighteen studies were included, comprising 16,095 patients. In the direct meta-analysis, SGLT2 inhibitors reduced HbA1c by 0.62% (95% CI −0.66 to −0.59) and body weight by 0.60 kg (95% CI −0.64 to −0.55). In the indirect meta-analysis, canagliflozin 300 mg ranked the highest regarding reductions in HbA1c and body weight. The remaining medications and dosages were clinically similar, despite some statistically significant differences among them. Canagliflozin 300 mg seems to be more potent in reducing HbA1c and body weight in patients with type 2 diabetes. The remaining SGLT2 inhibitors at different doses lead to similar effects for both outcomes. Whether these glycemic and weight effects are reflected in lower mortality and cardiovascular events is still uncertain and may be a topic for further studies.

Assuntos

RESUMO

We aimed to assess if GLP-1 agonists are associated with pancreatic cancer. Systematic review and meta-analysis of randomized trials with GLP-1 agonists as an intervention was performed. Trial sequential analysis (TSA) was performed to assess if the available information is sufficient to reject this association. Twelve trials met the study criteria, with a total of 36, 397 patients. GLP-1 analogues did not increase the risk for pancreatic cancer when compared to other treatments (OR 1.06; 95% CI 0.67 to 1.67; I2 14%). TSA confirmed that enough patients were randomized and again no association of the medications and pancreatic cancer was observed considering a NNH of 1000 and the short mean follow-up of the included trials (1.7 years). Larger studies with longer duration would be required to exclude a greater NNH and to aside concerns regarding possible influence of study duration and the outcome.

Assuntos

RESUMO

The use of dipeptidyl peptidase-4 (DPP-4) inhibitors may be associated with pancreatic cancer and acute pancreatitis. Recent meta-analyses have reported conflicting findings. Therefore, we performed a meta-analysis to assess the risk of both pancreatic cancer and acute pancreatitis associated with the use of DPP-4 inhibitors. We also used trial sequential analysis to evaluate whether the number of patients included was enough to reach conclusions. We included randomised controlled trials lasting 24 weeks or more that compared DPP-4 inhibitors with placebo or other antihyperglycaemic agents. A total of 59,404 patients were included. There was no relationship between the use of DPP-4 inhibitors and pancreatic cancer (Peto odds ratio 0.65; 95% CI 0.35-1.21), and the optimal sample size was reached to determine a number needed to harm (NNH) of 1000 patients. DPP-4 inhibitors were associated with increased risk for acute pancreatitis (Peto odds ratio 1.72; 95% CI 1.18-2.53), with an NNH of 1066 patients, but the optimal sample size for this outcome was not reached. In conclusion, there is no association between DPP-4 inhibitors and pancreatic cancer, and a small risk for acute pancreatitis was observed with DPP-4 inhibitor use, although the latter finding is not definitive.

Assuntos

RESUMO

OBJECTIVE: To evaluate the efficacy of coronary artery disease screening in asymptomatic patients with type 2 diabetes and assess the statistical reliability of the findings. METHODS: Electronic databases (MEDLINE, EMBASE, Cochrane Library and clinicaltrials.org) were reviewed up to July 2016. Randomised controlled trials evaluating coronary artery disease screening in asymptomatic patients with type 2 diabetes and reporting cardiovascular events and/or mortality were included. Data were summarised with Mantel-Haenszel relative risk. Trial sequential analysis (TSA) was used to evaluate the optimal sample size to detect a 40% reduction in outcomes. Main outcomes were all-cause mortality and cardiac events (non-fatal myocardial infarction and cardiovascular death); secondary outcomes were non-fatal myocardial infarction, myocardial revascularisations and heart failure. RESULTS: One hundred thirty-five references were identified and 5 studies fulfilled the inclusion criteria and totalised 3315 patients, 117 all-cause deaths and 100 cardiac events. Screening for coronary artery disease was not associated with decrease in risk for all-cause deaths (RR 0.95(95% CI 0.66 to 1.35)) or cardiac events (RR 0.72(95% CI 0.49 to 1.06)). TSA shows that futility boundaries were reached for all-cause mortality and a relative risk reduction of 40% between treatments could be discarded. However, there is not enough information for firm conclusions for cardiac events. For secondary outcomes no benefit or harm was identified; optimal sample sizes were not reached. CONCLUSION: Current available data do not support screening for coronary artery disease in patients with type 2 diabetes for preventing fatal events. Further studies are needed to assess the effects on cardiac events. PROSPERO: CRD42015026627.

Assuntos

RESUMO

OBJECTIVES: The aim of the present study was to evaluate the association of metabolic syndrome (MS) with periodontitis (PE) and tooth loss (TL). MATERIALS AND METHODS: A cross-sectional study was conducted with 363 individuals who underwent full-mouth periodontal examination, and the association between MS and PE was evaluated considering three outcomes: severe periodontitis, mean probing depth ≥2.4 mm, and mean clinical attachment loss ≥2.0 mm. The prevalence ratio (PR) between MS and PE was calculated using a model adjusted for gender, age, smoking, years of education, and socioeconomic status. RESULTS: The adjusted model showed a PR for severe periodontitis of 1.17 (95 % CI 0.83-1.65). There was no significant association between MS and PE defined as mean probing depth ≥2.4 mm. MS was significantly associated with PE defined as mean attachment loss ≥2 mm in individuals aged 41-60 years (PR 1.47, 95 % CI 1.05-2.06). In addition, MS was associated with TL (>6 teeth) (PR 1.23, 95 % CI 1.02-1.49) for all ages, both in crude and adjusted analyses. CONCLUSIONS: We concluded that there is a weak association of MS with both attachment loss and TL. CLINICAL RELEVANCE: Patients with MS seem to have a higher risk of attachment loss and tooth loss and should be screened for periodontal disease.

Assuntos

RESUMO

BACKGROUND AND AIMS: Diabetic kidney disease (DKD) is the leading cause of end stage renal disease worldwide and is associated with increased cardiovascular mortality. The endothelin system has been implicated in the pathogenesis of arterial hypertension and renal dysfunction. In the present study, the association of DKD with polymorphisms in ET-1 (EDN1) and ETRA (EDNRA) genes was analyzed in patients with type 2 diabetes mellitus (T2DM). METHODS: A case-control study was conducted in 548 white T2DM patients. Patients with proteinuria or on dialysis were considered cases and patients with normoalbuminuria were considered controls. Two polymorphisms in the EDN1 gene (rs1800541 and rs57072783) and five in EDNRA gene (rs6842241; rs4835083; rs4639051; rs5333 and rs5343) were genotyped and haplotype analyses were performed. RESULTS: The presence of rs57072783 T allele (TT/TG vs. GG) or rs1800541 G allele (GG/GT vs. TT) protected against DKD (OR = 0.69, 95 % CI 0.48-0.99, P = 0.049; and OR = 0.60, 95 % CI 0.41-0.88, P = 0.009, respectively). However in multivariate analyses, only the rs1800541 G allele remained independently associated with DKD (P = 0.046). CONCLUSIONS: The present study shows that ET-1 could be involved in the pathogenesis of DKD in patients with T2DM.

RESUMO

Data on the potential beneficial effects of combining diet and exercise on blood pressure (BP) are still scarce. A 4-week randomized controlled clinical trial was undertaken in 40 hypertensive patients with type 2 diabetes with uncontrolled blood pressure (BP) in office and daytime ambulatory BP monitoring (ABPM). Patients were assigned to follow a Dietary Approaches to Stop Hypertension (DASH) diet associated with advice to increase walking using a pedometer (intervention group) or a diet based on the American Diabetes Association recommendations (control group). The lifestyle intervention caused a greater ABPM (mm Hg) reduction in systolic 24-hour, diastolic 24-hour, nighttime systolic, daytime systolic, and daytime diastolic measurements than observed in the control group. In the intervention group there was a decrease in urinary sodium and an increase in urinary potassium, plasma aldosterone, and the number of steps per day (P<.05). The DASH diet and increased walking were associated with clinically significant reductions in ABPM values in hypertensive patients with type 2 diabetes.

Assuntos

RESUMO

Type 1 diabetes mellitus (T1DM) is associated with chronic complications that lead to high morbidity and mortality rates in young adults of productive age. Intensive insulin therapy has been able to reduce the likelihood of the development of chronic diabetes complications. However, this treatment is still associated with an increased incidence of hypoglycemia. In patients with "brittle T1DM", who have severe hypoglycemia without adrenergic symptoms (hypoglycemia unawareness), islet transplantation may be a therapeutic option to restore both insulin secretion and hypoglycemic perception. The Edmonton group demonstrated that most patients who received islet infusions from more than one donor and were treated with steroid-free immunosuppressive drugs displayed a considerable decline in the initial insulin independence rates at eight years following the transplantation, but showed permanent C-peptide secretion, which facilitated glycemic control and protected patients against hypoglycemic episodes. Recently, data published by the Collaborative Islet Transplant Registry (CITR) has revealed that approximately 50% of the patients who undergo islet transplantation are insulin independent after a 3-year follow-up. Therefore, islet transplantation is able to successfully decrease plasma glucose and HbA1c levels, the occurrence of severe hypoglycemia, and improve patient quality of life. The goal of this paper was to review the human islet isolation and transplantation processes, and to describe the establishment of a human islet isolation laboratory at the Endocrine Division of the Hospital de Clínicas de Porto Alegre - Rio Grande do Sul, Brazil.

Assuntos

RESUMO

Type 1 diabetes mellitus (T1DM) is associated with chronic complications that lead to high morbidity and mortality rates in young adults of productive age. Intensive insulin therapy has been able to reduce the likelihood of the development of chronic diabetes complications. However, this treatment is still associated with an increased incidence of hypoglycemia. In patients with “brittle T1DM”, who have severe hypoglycemia without adrenergic symptoms (hypoglycemia unawareness), islet transplantation may be a therapeutic option to restore both insulin secretion and hypoglycemic perception. The Edmonton group demonstrated that most patients who received islet infusions from more than one donor and were treated with steroid-free immunosuppressive drugs displayed a considerable decline in the initial insulin independence rates at eight years following the transplantation, but showed permanent C-peptide secretion, which facilitated glycemic control and protected patients against hypoglycemic episodes. Recently, data published by the Collaborative Islet Transplant Registry (CITR) has revealed that approximately 50% of the patients who undergo islet transplantation are insulin independent after a 3-year follow-up. Therefore, islet transplantation is able to successfully decrease plasma glucose and HbA1c levels, the occurrence of severe hypoglycemia, and improve patient quality of life. The goal of this paper was to review the human islet isolation and transplantation processes, and to describe the establishment of a human islet isolation laboratory at the Endocrine Division of the Hospital de Clínicas de Porto Alegre – Rio Grande do Sul, Brazil.

Assuntos