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The meta-analysis examined the association between GLP-1 receptor agonists and the risk of ischemic optic neuropathy in patients with obesity and/or type 2 diabetes. While some observational studies suggested a potential link, the meta-analysis of randomized controlled trials did not find a significant detrimental effect of GLP-1 RA therapy on optic neuropathy. The estimated incidence of optic ischemic neuropathy was higher in the GLP-1 RA arm compared to the placebo arm, but the difference was not statistically significant. Further research is needed to fully understand the safety profile of GLP-1 RA, especially in patients at higher risk for optic neuropathy. [Extracted from the article]

The study examined the glycaemic response to pasta made from three different wheat varieties in individuals with type 2 diabetes. The research found that there were no significant advantages in post-prandial glucose control when using ancient wheat varieties like Khorasan or Senatore Cappelli compared to the modern wheat variety Claudio. The macronutrient composition of the pasta was similar across all three varieties, and the differences in post-prandial glucose response were clinically trivial. The study suggests that individuals with type 2 diabetes can choose pasta based on personal taste preferences without worrying about minor differences in glucose levels. [Extracted from the article]

To verify the prevalence of positive Fibrosis-4 (FIB-4) score, a screening test for metabolic-associated liver disease, in a large population-based sample in the Tuscany Italian Region, and to identify sub-populations at higher risk which could be targeted by specific screening programs. Population-based survey performed in the Italian region of Tuscany, with Tuscany health informative system's administrative data. We included 594,923 subjects, of which 32% had available data for the FIB-4 calculation. The overall proportion of subjects with an FIB-4 value > 1.3, was 41.6% of those with available exams, and 12,8% of the whole population, whereas 5.4% and 1.7% had FIB-4 >2.67. In those younger than 80 years, FIB >1.3 had a 33.1% and 9.4%. People with diabetes mellitus had higher figures (52.8.% and 28.9% for FIB>1.3). Among subjects aged 70 years or over, 74.9% of those with available data and 38.4% of the general population had a FIB-4>1.3, whereas 32% and 16% had a FIB-4 > 2. The relevant proportion of FIB-4 positivity in the general population poses a significant burden for further screening with liver elastography. Targeting people with diabetes, excluding people older than 80 years and/or adopting a FIB-4 threshold of 2 in those aged more than 70 years could increase the cost-effectiveness of the screening procedures. • Individuals with a Fibrosis-4 (FIB-4 score) >1.3 should undergo liver elastography, according to Italian and international guidelines. • In a sample of Tuscan population free of liver disease, 12.8% (95%CI, 12.7%-12.8%) of subjects had FIB-4 >1.3. • If applying a 1.3 threshold for those < than 70 year old, and a 2 threshold for those ≥ 70 years, the prevalence would be 7.8% (95%CI, 7.7%-7.8%). • A higher prevalence was observed among people with diabetes: 28.9% (95% CI 28.5%-29.3%), but not in those with dyslipidemia. • Targeting people with diabetes and using 2 FIB-4 threshold in those >70 years may increase screening cost-effectivenes. [ABSTRACT FROM AUTHOR]

Metformin is the first‐line medication for type 2 diabetes. It is effective and safe, provided some caution is taken in specific populations. In patients with chronic kidney disease, metformin may provide long‐term benefits, and it is a first‐line therapy for diabetes, but the estimated glomerular filtration rate (eGFR) must be assessed regularly, to minimize the risk for metformin accumulation. When eGFR is 30‐60 mL/min/1.73m2, the dose should be reconsidered, and sick‐days education provided. Metformin should be discontinued when eGFR falls below 30 mL/min/1.73m2. Metformin accumulation may increase the risk for lactic acidosis if concomitant risk factors for hyperlactataemia (liver or respiratory insufficiency, sepsis, acute heart failure) are present; in these conditions, metformin is contraindicated, even although the available evidence is reassuring. Patients on metformin often complain of gastrointestinal side effects (mainly diarrhoea and nausea) during therapy initiation, but they may sometimes occur after years of stable therapy. These usually resolve if the dose is carefully titrated, or by switching to the extended‐release formulation. Patients with obesity may benefit from the significant, although modest, metformin‐associated weight loss and appetite reduction. During pregnancy, metformin is associated with a reduction of pregnancy complications, especially in obese women, but some concern remains, because metformin crosses the placenta, and it is associated with a significantly lower mean birth weight than insulin. In the elderly, gastrointestinal tolerability and renal function must be reassessed more often. Vitamin B‐12 should be screened regularly in long‐time metformin users because metformin may induce clinical vitamin B‐12 deficiency. [ABSTRACT FROM AUTHOR]

A meta-analysis of randomized controlled trials was conducted to investigate the potential link between glucagon-like peptide-1 receptor agonists (GLP-1RA) and mental health. GLP-1 receptors are found in the central nervous system and have effects on neurocognitive functions, inflammation, stress response, and energy metabolism. The analysis included 31 studies with a total of 84,713 patients and found no significant difference in the incidence of psychiatric disorders, suicidal behavior, depression, or anxiety between GLP-1RA and placebo. However, the study acknowledged limitations, such as the exclusion of patients with severe mental illnesses in clinical trials and the need for further research on GLP-1RA effects in patients with pre-existing psychiatric disorders. [Extracted from the article]

Aim: To conduct a meta‐analysis of randomized clinical trials (RCTs) to investigate whether there is an association between glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) treatment and thyroid cancer. Materials and Methods: In this meta‐analysis of RCTs, we included studies comparing a GLP‐1RA with any comparator, lasting at least 52 weeks, and reporting the incidence of adverse events independently of the principal endpoint and population. All cases of thyroid cancer were collected. Results: We retrieved 64 trials, 26 of which reported at least one incident case of thyroid cancer. GLP‐1RA treatment was associated with a significant increase in the risk of overall thyroid cancer (Mantel‐Haenzel odds ratio [MH‐OR] 1.52 [95% confidence interval {CI} 1.01, 2.29]; P = 0.04, I2 = 0%), with a fragility index of 1, and a 5‐year number needed to harm of 1349. The association remained significant when including only trials lasting at least 104 weeks (MH‐OR 1.76 [95% CI 1.00, 3.12]; P = 0.05). No significant association was found for papillary thyroid cancer (MH‐OR 1.54 [95% CI 0.77, 3.06]; P = 0.22) or medullary thyroid cancer (MH‐OR 1.44 [95% CI 0.23, 9.16]; P = 0.55). Conclusions: Our meta‐analysis showed that GLP‐1RA treatment could be associated with a moderate increase in relative risk for thyroid cancer in clinical trials, with a small increase in absolute risk. Studies of longer duration are required to assess the clinical implications of this finding. [ABSTRACT FROM AUTHOR]

Aim: To compare different types of metabolic surgery with non‐surgical therapy for the treatment of type 2 diabetes (T2D). Methods: The present network meta‐analysis (NMA) includes randomized clinical trials (duration ≥ 52 weeks) comparing different surgery techniques with non‐surgical therapy in diabetes patients. The primary endpoints were endpoint HbA1c, body mass index (BMI) and diabetes remission. The secondary endpoints included fasting plasma glucose, lipid profile, blood pressure, arterial hypertension and dyslipidaemia remission, quality of life and surgical adverse events. Indirect comparisons of different types of surgery were performed by NMA. Mean and 95% confidence intervals for continuous variables, and the Mantel–Haenzel odds ratio for categorial variables, were calculated. Results: The types of surgical procedure included laparoscopic adjustable gastric banding, Roux‐en‐Y gastric bypass (RYGB), sleeve gastrectomy (SG), bilio‐pancreatic diversion (BPD), greater curvature plication (GCP), one‐anastomosis gastric bypass (OAGB) and Duodeno–Jejunal bypass. Thirty‐six trials were included. Metabolic bariatric surgery (MBS) was associated with a significantly higher reduction of HbA1c, diabetes remission and BMI compared with medical therapy. In the NMA, a significant reduction of HbA1c was observed with OAGB and SG. Complete diabetes remission significantly increased with all surgical procedures in comparison with non‐surgical therapy, except for GCP. In addition, only BPD, RYGB and OAGB were associated with a significant reduction of BMI. Conclusions: MBS is an effective option for the treatment of T2D in patients with obesity. Further long‐term trials of appropriate quality are needed for assessing the risk–benefit ratio in some patient cohorts, such as those with a BMI of less than 35 kg/m2 and aged older than 65 years. [ABSTRACT FROM AUTHOR]

The present meta‐analysis is aimed at assessing the effects of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors on all‐cause mortality and differences across different trials and molecules of the class. We included all randomized clinical trials with a duration of treatment longer than 52 weeks, enrolling at least 100 patients in each arm, and comparing an SGLT2 inhibitor with any comparator or placebo. Out of 139, 235 and 145 items identified, 21 trials were selected, enrolling 39 593 and 30 771 patients in SGLT2 inhibitor and comparator arms, respectively, with a median duration of 104 weeks, and reporting 2474 and 2298 deaths for SGLT2 inhibitors and comparators, respectively. No relevant heterogeneity was found (I2 = 17%). Treatment with SGLT2 inhibitors was associated with a significant reduction in all‐cause mortality (MH‐OR [95% CI] 0.86 [0.81, 0.91] P <.00001). Meta‐regression analyses found a significant direct association of treatment effect only with the proportion of Asian subjects enrolled, and an inverse correlation with the proportion of Caucasian patients. In conclusion, SGLT2 inhibitors reduce all‐cause mortality in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Fournier's gangrene (FG) is a rare, life‐threatening necrotizing fasciitis of the perineum. The US Food and Drug Administration (FDA) released a Drug Safety Communication regarding the risk of FG associated with sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i), relying on the FDA Adverse Event Reporting System. To verify this association, we performed a meta‐analysis of all randomized controlled trials enrolling patients with type 2 diabetes, comparing SGLT2i with placebo or different therapies, collecting cases of FG reported as a serious adverse event. Risk of abscess, cellulitis and erysipela were secondary outcomes. We retrieved 84 trials enrolling 42 415 patients in the SGLT2i group and 27 158 patients in comparator groups. No difference was observed between SGLT2i and comparators in the risk of FG (Mantel‐Haenzel odds ratio [MH‐OR] 0.41 [0.09, 1.82]), abscess (MH‐OR 0.94 [0.54, 1.65]), cellulitis (MH‐OR 0.90 [0.71, 1.13] or erysipela (MH‐OR 0.89 [0.45, 1.77]). The number of events was small, leading to a wide confidence interval that does not allow ruling out an increase in FG or skin and subcutaneous tissue infections. [ABSTRACT FROM AUTHOR]