Efficacy and safety of GLP-1 receptor agonists as add-on to SGLT2 inhibitors in type 2 diabetes mellitus: A meta-analysis.

GLP-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i) have been associated with improved glycemic control, body weight loss and favorable changes in cardiovascular risk factors and outcomes. We conducted a systematic review and meta-analysis to evaluate the effects of the addition of GLP-1RA to SGLT2i in patients with type 2 diabetes mellitus and inadequate glycemic control. Six databases were searched until March 2019. Randomized controlled trials (RCT) with a follow-up of at least 24 weeks reporting on HbA1c, body weight, systolic blood pressure, lipids, achievement of HbA1c < 7%, requirement of rescue therapy due to hyperglycemia and hypoglycemic events were selected. Four RCTs were included. Compared to SGLT2i, the GLP-1RA/SGLT2i combination was associated with greater reduction in HbA1c (-0.74%), body weight (-1.61 kg), and systolic blood pressure (-3.32 mmHg). A higher number of patients achieved HbA1c < 7% (RR = 2.15), with a lower requirement of rescue therapy (RR = 0.37) and similar incidence of hypoglycemia. Reductions in total and LDL cholesterol were found. The present review supports treatment intensification with GLP-1RA in uncontrolled type 2 diabetes on SGLT2i. This drug regimen could provide improved HbA1c control, together with enhanced weight loss and blood pressure and lipids control.

Effects of CPAP on Testosterone Levels in Patients With Obstructive Sleep Apnea: A Meta-Analysis Study.

Background: Obstructive sleep apnea (OSA) represents a frequent complication among patients with obesity and has been associated with neuroendocrine changes, including hypogonadism. Objective: We conducted a systematic review and meta-analysis to evaluate the effects of continuous positive airway pressure (CPAP) on testosterone and gonadotropins in male patients with OSA. Methods: The review was registered on PROSPERO (CRD42018103164). PubMed, Scopus, CENTRAL, and Clinicaltrials.gov were searched until June 2018. Studies reporting the effect of CPAP on total testosterone, free testosterone, sexual hormone binding globulin (SHBG), follicle stimulating hormone (FSH), luteinizing hormone (LH), and prolactin were included. A subgroup analysis on hypogonadal vs. eugonadal status at baseline was performed. Results: Out of 129 retrieved papers, 10 prospective cohort and 2 randomized controlled studies were included in the review. Three hundred eighty-eight patients were included. CPAP use was not associated with a significant change in total testosterone levels [mean difference 1.08, 95% confidence interval (CI) -0.48 to 2.64] or other outcomes. The subgroup analysis confirmed the overall results. Conclusions: The present review does not support the hypothesis of a direct interaction between OSA and testosterone. Strategies other than CPAP should therefore be considered in managing hypogonadism in patients with OSA.

GLP-1 receptor agonist added to insulin versus basal-plus or basal-bolus insulin therapy in type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: Current guidelines recommend that antihyperglycaemic treatment in patients with type 2 diabetes not achieving the HbA1c target on basal insulin should be intensified with a glucagon-like peptide-1 receptor agonist (GLP-1RA) or basal-plus/basal-bolus (BP/BB) insulin regimen. We conducted a systematic review and meta-analysis to compare the effects of GLP-1RA/insulin combinations versus BP/BB. METHODS: The review was registered on PROSPERO (CRD42017079547). PubMed, Scopus, CENTRAL, and ClinicalTrials.gov were searched until July 2018. All randomized controlled trials (RCTs) reporting HbA1c , body weight, daily insulin dose, hypoglycaemic events, and discontinuation due to lack of efficacy were included. A subgroup analysis on different combinations of GLP-1RA and insulin was performed. RESULTS: Out of 1885 retrieved papers, 13 RCTs were included in the review. Compared with BP/BB, GLP-1RA/insulin combinations were associated with a similar HbA1c reduction (Δ = -0.06%; 95% confidence interval [CI], -0.14 to 0.02; P = 0.13; I2  = 52%), greater weight loss (Δ = -3.72 kg; 95% CI, -4.49 to -2.95; P < 0.001; I2  = 89%), and lower incidence of hypoglycaemic events (relative risk [RR] = 0.46; 95% CI, 0.38-0.55; P < 0.001; I2  = 99%). The daily insulin dosage among GLP-1RA/insulin users was 30.3 IU/day (95% CI, -41.2 to -19.3; P < 0.001; I2  = 94%), lower than with BP/BB. No difference was found for discontinuation due to lack of efficacy. CONCLUSIONS: The present review supports treatment intensification with GLP-1RA added to insulin versus BP/BB in uncontrolled type 2 diabetes. This could provide similar antihyperglycaemic efficacy while leading to weight loss and sparing of hypoglycaemia and insulin dose. As a consequence, a considerable number of patients with type 2 diabetes could be potentially shifted from BP/BB to GLP-1RA/insulin combinations.

Concomitant psychiatric problems and hormonal treatment induced metabolic syndrome in gender dysphoria individuals: a 2 year follow-up study.

OBJECTIVE: Several studies indicate increased prevalence of metabolic syndrome (MetS) among patients with psychiatric disorders as well as among individuals with gender dysphoria (GD) treated by cross-sex hormonal treatment. However, the MetS prevalence among hormone treated GD individuals suffering from psychiatric problems has not been detected. METHODS: From a sample of 146 GD patients we selected 122 metabolically healthy individuals in order to investigate the prevalence of MetS after the beginning of the cross-sex hormonal treatment in a 2 year follow-up assessment. Furthermore, we assessed differences in MetS prevalence between hormone treated GD patients with and without concomitant psychiatric problems. RESULTS: When treated with hormone therapy, GD patients reported changes in several parameters which are clustered in MetS, with statistically significant differences compared to baseline. Glyco-insulinemic alterations were more pronounced in male to female patients (MtFs). However, weight gain, waist circumference increases, blood pressure increases, and lipid alterations were similar in MtFs and female to male patients (FtMs). 14.8% of the sample at year 1 and 17.2% at year 2 developed MetS. Among patients with concomitant psychiatric problems, 50% at year 1 and 55% at year 2 developed MetS against 8% at year 1 and 10% at year 2 of patients without concomitant psychiatric problems. CONCLUSION: This study indicates that sex hormones induce MetS in a relatively low proportion of healthy GD individuals and especially during the first year of hormonal treatment. Most importantly, concomitant psychiatric problems are associated with considerably greater MetS prevalence in hormone treated GD individuals.

Effects of combined treatment with simvastatin and L-carnitine on triglyceride levels in diabetic patients with hyperlipidaemia.

OBJECTIVE: To investigate the effects of L-carnitine, coadministered with simvastatin, on hypercholesterolaemia and hypertriglyceridaemia in patients with diabetes. DESIGN: Randomised, open, parallel-group study. SETTING: One investigational centre (hospital). PATIENTS: Thirty-two patients with type 2 diabetes mellitus and hyperlipidaemia (total cholesterol levels > 200 mg/dl and triglyceride levels >150 mg/dl). INTERVENTIONS: PATIENTS were randomised to receive simvastatin alone (n = 16) or simvastatin plus L-carnitine (n = 16) for 60 days. Both treatments were given orally. Simvastatin was administered, in both groups, at a dosage of 20 mg/day, while L-carnitine was administered at a dosage of 2000 mg/day twice daily. MAIN OUTCOME MEASURES AND RESULTS: Plasma levels of triglycerides, total cholesterol and high-density lipoprotein (HDL) cholesterol were measured at baseline and at 30 and 60 days after starting treatment. In both groups, there was a progressive improvement in all measured parameters during the study period. However, triglyceride levels decreased to a significantly greater extent in patients co-treated with L-carnitine (from 266.8 mg/dl at baseline to 153.8 mg/dl at 60 days) compared with those receiving simvastatin alone (from 300.2 to 227.8 mg/dl, respectively; p = 0.012 vs combined treatment). HDL-cholesterol levels increased from 49.8 mg/dl at baseline to 51.8 mg/dl at 60 days in the combined treatment group, and decreased from 51.2 to 47.8 mg/dl, respectively in simvastatin recipients, with a trend in favour of the combined treatment (p = 0.076), while no significant differences between groups were observed for total cholesterol levels. CONCLUSIONS: Combined treatment with L-carnitine and simvastatin resulted in greater antihyperlipidaemic effects (i.e. a less atherogenic plasma lipid profile) than with simvastatin alone. The results of this preliminary study strongly suggest that L-carnitine may have a role among antihyperlipidaemic strategies.