Sodium-glucose cotransporter-2 inhibitors and cancer outcomes: A systematic review and meta-analysis of randomized controlled trials.

AIMS: Concerns regarding breast and bladder cancer risk with Sodium-glucose cotransporter-2 (SGLT2) inhibitors remain controversial and its effect on cancer mortality is unknown. We aim to evaluate the association between SGLT2 inhibitors and the risk of cancer outcomes. METHODS: We searched PubMed, Embase and CENTRAL up to June 20th, 2022, for randomized controlled trials of SGLT2 inhibitors in adults, with a minimum follow-up of 48 weeks. Researchers extracted study-level data and assessed within-study risk of bias with the RoB 2.0 tool and quality of evidence with GRADE. We performed meta-analyses summarizing the relative risks (RRs) of cancer outcomes. RESULTS: Seventy-six trials encompassing 116,375 participants were selected. Overall risk of bias was low. SGLT2 inhibitors did not reduce/increase the overall risk of cancer (RR, 1.03; 95% confidence interval [CI], 0.96-1.10) and cancer mortality (RR, 0.99; 95% CI, 0.85-1.16). SGLT2 inhibitors likely result in little to no difference in the risk of breast (RR, 1.01; 95% CI 0.77-1.32) and bladder cancers (RR, 0.93; 95% CI 0.71-1.21). Trial sequential analysis provided evidence that the sample size was sufficient to avoid missing alternative results. CONCLUSIONS: SGLT2 inhibitors are not associated with an increased risk of cancer outcomes, providing reassuring data regarding previous safety concerns.

Do GLP-1 Receptor Agonists Increase the Risk of Breast Cancer? A Systematic Review and Meta-analysis.

CONTEXT: Risk of cancer is a major concern in the development of drugs for the treatment of obesity and diabetes. In randomized controlled trials (RCTs) of the Liraglutide Clinical Development Program, subjects treated with a glucagon-like peptide-1 receptor agonist (GLP-1RA) had a higher absolute number of breast cancer events. OBJECTIVE: To assess whether patients treated with GLP-1RAs had a higher risk of breast neoplasms. DATA SOURCES: We searched MEDLINE, Embase, Web of Science, and CENTRAL from July 31, 2019 to February 8, 2020. STUDY SELECTION: Reviewers assessed abstracts and full-text articles for RCTs of GLP-1RAs in adults with excessive weight and/or diabetes and a minimum follow-up of 24 weeks. DATA EXTRACTION: Researchers extracted study-level data and assessed within-study risk of bias with the RoB 2.0 tool and quality of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). DATA SYNTHESIS: We included 52 trials, of which 50 reported breast cancer events and 11 reported benign breast neoplasms. Overall methodological quality was high. Among 48 267 subjects treated with GLP-1RAs, 130 developed breast cancer compared with 107 of 40 755 controls (relative risk [RR], 0.98; 95% confidence interval [CI], 0.76-1.26). Subset analyses according to follow-up, participant/investigator blinding, and type of GLP-1RA did not reveal any differences. The risk of benign breast neoplasms also did not differ between groups (RR, 0.99; 95% CI, 0.48-2.01). Trial sequential analysis provided evidence that the sample size was sufficient to avoid missing alternative results. CONCLUSIONS: Treatment with GLP-1RAs for obesity and diabetes does not increase the risk of breast neoplasms.

Low linolenic and linoleic acid consumption are associated with chronic kidney disease in patients with type 2 diabetes.

AIM: This cross-sectional study aimed to assess the association of the fat content in the diet with Diabetic Kidney Disease (DKD) in patients with type 2 diabetes. METHODOLOGY: Patients from the Diabetes research clinic at Hospital de Clínicas de Porto Alegre (Brazil) were consecutively recruited. The inclusion criterion was the diagnosis of type 2 diabetes. The exclusion criteria were as follows: body mass index >40 kg/m2, heart failure, gastroparesis, diabetic diarrhea, dietary counseling by a registered dietitian during the previous 12 months, and inability to perform the weighed diet records (WDR). The dietary fatty acids (saturated, monounsaturated and polyunsaturated) consumption was estimated by 3-day WDR. Compliance with the WDR technique was assessed by comparison of protein intake estimated from the 3-day WDR and from the 24-h urinary nitrogen output performed on the third day of the WDR period. The presence of DKD was defined as urinary albumin excretion (UAE) ≥ 30 mg / 24 h or/and glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Urinary albumin was measured twice and eGFR was estimated by using the CKD-EPI equation. RESULTS: A total of 366 patients were evaluated; of these, 33% (n = 121) had DKD. Multivariate analysis showed that the intake of linolenic acid was negatively associated with DKD (OR = 0.57; 95% CI 0.35-0.93; P = 0.024), adjusted for gender, smoking, cardiovascular disease, ACE inhibitors and/or angiotensin receptor blocker use, systolic blood pressure, fasting plasma glucose and HDL cholesterol. In a separate model, similar results were observed for linoleic acid, adjusting to the same co-variables (OR = 0.95; 95% CI 0.91-0.99; P = 0.006). CONCLUSION: The lower intake of polyunsaturated fatty acids, especially linolenic and linoleic acid, is associated with chronic kidney disease in patients with type 2 diabetes.