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BACKGROUND: No comprehensive meta-analysis has examined and consolidated the effectiveness and safety of anagliptin in treating type 2 diabetes mellitus (T2D). To bridge this knowledge gap, we undertook this meta-analysis. METHODS: Randomized controlled trials involving patients with T2D receiving anagliptin were sought after through electronic databases. The control arm consisted of either an active comparator (active control group [ACG]) or a placebo (passive control group [PCG]). The primary outcome was glycated hemoglobin (HbA1c), with secondary outcomes including fasting plasma glucose (FPG) and lipid profiles and adverse events. RESULTS: From the 226 articles first examined, 10 randomized controlled trials with 970 participants were analyzed. Reductions in HbA1c (mean difference [MD]: -0.03%, 95% confidence interval [CI]: -0.14 to 0.14, Pâ =â .51, I2 = 9%) and FPG (MD: 0.03 mmol/L, 95% CI: -0.30 to 0.35, Pâ =â .87, I2 = 42%) were similar in the anagliptin group and ACG. Anagliptin reduced FPG better than placebo (MD: -1.25 mmol/L, 95% CI: -1.87 to -0.64, Pâ <â .0001, I2 = 0%). Sufficient data were unavailable to analyze the HbA1c lowering with anagliptin versus placebo. Among the lipid parameters, changes in total cholesterol, high-density lipoprotein cholesterol, apolipoprotein B48, and apolipoprotein B100 were identical between the anagliptin and control groups (PCG and ACG). Anagliptin was better than ACG at lowering low-density lipoprotein cholesterol but not as good at lowering triglyceride. Adverse events were infrequent and similar in the anagliptin and control groups (PCG and ACG). CONCLUSION: Anagliptin positively affects glucose control and is safe for managing T2D. Its low-density lipoprotein cholesterol-lowering effect warrants further investigation.
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Glucemia , Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Hemoglobina Glucada , Pirimidinas , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Humanos , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Pirimidinas/uso terapéutico , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/análisis , Glucemia/efectos de los fármacos , Ensayos Clínicos Controlados Aleatorios como Asunto , Lípidos/sangreRESUMEN
OBJECTIVE: Data are scant on the impact of metformin use in gestational diabetes mellitus/diabetes in pregnancy on long-term outcomes in children and mothers beyond 5 years of childbirth. This systematic review and meta-analysis aimed to evaluate the long-term impact of metformin use in pregnancy on children and their mothers. METHODS: Electronic databases were searched for studies evaluating metformin compared with insulin for managing gestational diabetes mellitus/diabetes in pregnancy. The primary outcome was the change in body mass index (BMI) in children at the ages of 5 to 11 years. The secondary outcomes were alterations in other anthropometric measures, obesity, and changes in the levels of lipids and adipocytokines in children and mothers. RESULTS: Children at the age of 9 years born to mothers who were treated with metformin during pregnancy had similar BMI (mean difference [MD], 1.09 kg/m2 [95% confidence interval {CI}, -0.44 to 2.62]; P = .16; I2 = 16%), waist circumference-to-height ratio (MD, 0.13 [95% CI, -0.05 to 0.30]; P = .16; I2 = 94%), dual-energy X-ray absorptiometry (DXA) total fat mass (MD, 0.68 kg [95% CI, -2.39 to 3.79]; P = .66; I2 = 70%), DXA total fat percent (MD, 0.04% [95% CI, -3.44 to 3.51]; P = .98; I2 = 56%), DXA total fat-free mass (MD, 0.81 kg [95% CI, -0.96 to 2.58]; P = .37; I2 = 55%), magnetic resonance imaging visceral adipose tissue volume (MD, 80.97 cm3 [95% CI, -136.47 to 298.41]; P = .47; I2 = 78%), and magnetic resonance spectroscopy liver fat percentage (MD, 0.27% [95% CI, -1.26 to 1.79]; P = .73; I2 = 0%) to those born to mothers who were treated with insulin. Serum adiponectin, leptin, alanine aminotransferase, and ferritin were comparable among groups. In children between the ages of 9 and 11 years, the occurrence of obesity, diabetes, or challenges in motor and social development were comparable between the 2 groups. After 9 years of childbirth, BMI and the risk of developing diabetes were similar between the 2 groups of women. CONCLUSION: Metformin use in pregnancy did not show any adverse effects compared with insulin on long-term outcomes in children and their mothers.
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INTRODUCTION: Preclinical and animal studies have suggested that excess catecholamines can lead to bone mineral loss. However, to date, no systematic review is available that has analyzed the impact of catecholamine excess in the context of pheochromocytoma/paraganglioma (PPGL) on bone metabolism. We conducted this meta-analysis to address this knowledge gap. METHODS: Electronic databases were searched for studies evaluating bone metabolism, including assessments of bone mineral density (BMD), quantitative computed tomography (qCT), trabecular bone score (TBS), or bone turnover markers in patients with PPGL. These markers included those of bone resorption, such as tartrate-resistant acid phosphatase 5b (TRACP-5b) and cross-linked C-telopeptide of type I collagen (CTx), as well as markers of bone formation, such as bone-specific alkaline phosphatase (BS ALP). RESULTS: Out of the initially screened 1614 articles, data from six studies published in four different patient cohorts with PPGL that met all criteria were analysed. Individuals with PPGL had significantly lower TBS [Mean Difference (MD) -0.04 (95% CI: -0.05--0.03); p < 0.00001; I2â¯=â¯0%], higher serum CTx [MD 0.13 ng/ml (95% CI: 0.08-0.17); p < 0.00001; I2â¯=â¯0%], and higher BS-ALP [MD 1.47 U/L (95% CI: 0.30-2.64); pâ¯=â¯0.01; I2â¯=â¯1%]. TBS at 4-7 months post-surgery was significantly higher compared to baseline [MD 0.05 (95% CI: 0.02-0.07); p < 0.0001]. A decrease in CTx has been documented post-surgery. CONCLUSION: Bone health deterioration is a major concern in patients with PPGL. In addition to providing a definitive cure for catecholamine excess, monitoring and treating osteoporosis is essential for individuals with secondary osteoporosis due to PPGL. Long-term studies on bone health outcomes in PPGL are warranted.
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Neoplasias de las Glándulas Suprarrenales , Densidad Ósea , Remodelación Ósea , Paraganglioma , Feocromocitoma , Humanos , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/metabolismo , Feocromocitoma/diagnóstico por imagen , Feocromocitoma/metabolismo , Paraganglioma/diagnóstico por imagen , Fosfatasa Alcalina/sangre , Hueso Esponjoso/diagnóstico por imagen , Resorción Ósea/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Huesos/metabolismo , Huesos/diagnóstico por imagen , Colágeno Tipo I/sangre , Fosfatasa Ácida Tartratorresistente/sangre , Fosfatasa Ácida Tartratorresistente/metabolismo , PéptidosRESUMEN
BACKGROUND: A significant number of patients face the issue of weight gain (WG) or inadequate weight loss (IWL) post-bariatric surgery for obesity. Several studies have been published evaluating the role of glucagon-like peptide-1 receptor agonists (GLP1RA) for weight loss post-bariatric surgery. However, no systematic review and meta-analysis (SRM) till date has evaluated the efficacy, safety and tolerability of GLP1RA in this clinical scenario. Hence, this SRM aimed to address this knowledge gap. METHODS: Databases were searched for randomized controlled trials (RCTs), case-control, cohort and observational studies involving use of GLP1RA in the intervention arm post-bariatric surgery. Primary outcome was weight loss post at least 3 months of therapy. Secondary outcomes were evaluation of body composition parameters, total adverse events (TAEs) and severe adverse events (SAEs). RESULTS: From initially screened 1759 articles, 8 studies (557 individuals) were analysed. Compared to placebo, patients receiving liraglutide had significantly greater weight loss after 6-month therapy [MD - 6.0 kg (95% CI, - 8.66 to - 3.33); P < 0.001; I2 = 79%]. Compared to liraglutide, semaglutide had significantly greater percent reduction in body weight after 6-month [MD - 2.57% (95% CI, - 3.91 to - 1.23); P < 0.001; I2 = 0%] and 12-month [MD - 4.15% (95% CI, - 6.96 to - 1.34); P = 0.004] therapy. In study by Murvelashvili et al. (2023), after 12-month therapy, semaglutide had significantly higher rates of achieving > 15% [OR 2.15 (95% CI, 1.07-4.33); P = 0.03; n = 207] and > 10% [OR 2.10 (95% CI, 1.19-3.71); P = 0.01; n = 207] weight loss. A significant decrease in fat mass [MD - 4.78 kg (95% CI, - 7.11 to - 2.45); P < 0.001], lean mass [MD - 3.01 kg (95% CI, - 4.80 to - 1.22); P = 0.001] and whole-body bone mineral density [MD - 0.02 kg/m2 (95% CI, - 0.04 to - 0.00); P = 0.03] was noted with liraglutide. CONCLUSION: Current data is encouraging regarding use of GLP1RAs for managing WG or IWL post-bariatric surgery. Deterioration of bone health and muscle mass remains a concern needing further evaluation. TRIAL REGISTRATION: The predefined protocol has been registered in PROSPERO having registration number of CRD42023473991.
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Cirugía Bariátrica , Diabetes Mellitus Tipo 2 , Obesidad Mórbida , Humanos , Liraglutida/farmacología , Liraglutida/uso terapéutico , Agonistas Receptor de Péptidos Similares al Glucagón , Obesidad Mórbida/cirugía , Pérdida de Peso , Hipoglucemiantes/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/cirugíaRESUMEN
Background: Orforglipron is a novel once-daily oral non-peptide glucagon-like peptide-1 receptor agonist with several recently published randomized controlled trials (RCTs) evaluating its role in diabetes and obesity. No meta-analysis has analyzed the efficacy and safety of orforglipron; this meta-analysis aimed to address this knowledge gap. Methods: A systematic search was conducted in electronic databases to identify RCTs that included individuals with obesity who were administered orforglipron and compared to either a placebo or an active comparator. The primary outcome of interest was the percent change in body weight. Results: From 12 initially screened articles, data from three RCTs involving 774 people were analyzed with a follow-up duration of up to 36 weeks. Compared to placebo, patients receiving orforglipron 12 mg/day (mean difference (MD), MD -5.48%, 95% CI [-7.64, -3.33], p < 0.01), 24 mg/day (MD -8.51%, 95% confidence interval (CI) [-9.88, -7.14], p < 0.01), 36 mg/day (MD -8.84%, 95% CI [-11.68, -6.00], p < 0.01) and 45 mg/day (MD -8.24%, 95% CI [-12.84, -3.63], p < 0.01) had a significantly greater percent reduction in body weight. The percentage of patients being able to achieve >15% weight loss from baseline was significantly higher with orforglipron 24 mg/day [Odds ratio (OR) 21.90 (95% CI [4.06, 118.15], p = 0.0003), 36 mg/day (OR 17.43, 95% CI [3.18, 95.66], p = 0.001) and 45 mg/day (OR 23.17, 95% CI [4.37, 123.03], p = 0.0002). Total but not severe adverse events were significantly higher with all the doses of orforglipron compared to placebo, with the hazard ratios being higher with higher doses. Gastrointestinal side-effects were predominant side effects, being dose-dependent, with nausea, vomiting, constipation, and gastroesophageal reflux being the predominant ones. Conclusion: Orforglipron at 24-45 mg/day doses is an effective weight loss medication. The efficacy versus side effect profile suggests that 24-36 mg/day is the most optimal dose for orforglipron as an anti-obesity medicine.
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PURPOSE: Sodium glucose cotransporter-2 inhibitors (SGLT2i) have been evaluated in children with type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM), and several other nondiabetic conditions. Potential tolerability issues have prevented the routine use of SGLT2i in children with diabetes. However, no meta-analysis to date has evaluated the safety and tolerability of SGLT2i in children. This systematic review and meta-analysis aimed to address this knowledge gap. METHODS: Databases were searched for randomized controlled trials (RCTs), case control, and cohort studies involving children receiving SGLT2i in the intervention-arm. Primary outcome was occurrence of treatment emergent adverse events (TAEs). Secondary outcomes were evaluation of glycemic efficacy and occurrence of severe adverse events (SAEs), hypoglycemia, ketosis, genital or urinary infections, and any other adverse events. RESULTS: From the 27 articles initially screened, data from 4 RCTs (258 children) were analyzed. In children with T2DM, occurrence of TAEs (odds ratio [OR], 1.77; 95% confidence interval [CI], 0.93-3.36; P=0.08; I2=0%), SAEs (OR, 0.45; 95% CI, 0.08-2.54; P=0.37; I2=0%), ketoacidosis (OR, 0.33; 95% CI, 0.01-8.37; P=0.50), urinary tract infections (OR, 2.34; 95% CI, 0.44-12.50; P=0.32; I2=0%), and severe hypoglycemia (OR, 4.47; 95% CI, 0.21-96.40; P=0.34) were comparable among the SGLTi group and placebo. Compared to placebo, T2DM children receiving SGLTi had significantly lower glycosylated hemoglobin at 24-26 weeks (mean difference [MD], -0.79%; 95% CI, -1.33 to -0.26; P=0.004; I2=0%). In T1DM children, ß-hydroxybutyrate levels were significantly higher in the SGLTi group than the placebo group (MD, 0.11 mmol/L; 95% CI, 0.05-0.17; P=0.0005; I2=53%). In T1DM, there was not a single report of an SAE, ketoacidosis, or severe hypoglycemia in either the placebo or treatment groups, but time-in-range was considerably greater in the SGLT2i group than the placebo group (68%±6% vs. 50%±13%, P<0.001). CONCLUSION: SGLT2i use in children and young adults appears to be both safe and tolerable based on our meta-analyses and review of the literature.
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Background: Polyethylene glycol loxenatide (peg-loxenatide) is a novel glucagon-like peptide-1 receptor agonist developed and available for clinical use in China. This meta-analysis was performed as no meta-analysis has analysed the efficacy and safety of peg-loxenatide in type 2 diabetes (T2DM). Methods: Electronic databases were systematically reviewed for RCTs having patients living with T2DM receiving peg-loxenatide in treatment arm and placebo/any other diabetes medicine in control arm. The primary outcome was to evaluate changes in glycated haemoglobin. The secondary outcomes were to evaluate alterations in weight, blood pressure, fasting glucose, prandial glucose, lipids, and adverse events. Results: Data from four trials (718 patients) were analysed. Over 12-24 weeks of clinical use, HbA1c was significantly lower in patients receiving standard-dose peg-loxenatide (100 mcg/week) {MD -0.95% [95% confidence interval (CI): -1.19 to -0.71]; P < 0.01; I2 = 76%} and high-dose peg-loxenatide (200 mcg/week) [MD -1.15% (95% CI: -1.47 to -0.82); P < 0.01; I2 = 90%], as compared to placebo. Standard-dose peg-loxenatide was not associated with increased occurrence of nausea [RR 2.87 (95% CI: 0.56 to 14.72); P = 0.21; I2 = 10%], vomiting [RR 4.73 (95% CI: 0.53 to 41.88); P = 0.16; I2 = 0%], and anorexia [RR 0.78 (95% CI: 0.18 to 3.28); P = 0.73; I2 = 0%]. Occurrence of nausea [RR 16.85 (95% CI: 3.89 to 72.92); P < 0.01; I2 = 10%], vomiting [RR 15.90 (95% CI: 2.99 to 84.55); P < 0.01; I2 = 0%], and anorexia [RR 3.85 (95% CI: 1.24 to 11.88); P = 0.02; I2 = 0%] was significantly higher with high-dose peg-loxenatide, as compared to placebo. Conclusion: Peg-loxenatide (100 mcg/week) is the most appropriate dose for clinical use as it is associated with good glycaemic efficacy with minimal gastro-intestinal side effects.
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No meta-analysis has analyzed the safety and efficacy of rivoglitazone in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge gap. Electronic databases were searched for RCTs involving T2DM patients receiving rivoglitazone in the intervention arm, and placebo/active comparator in the control arm. The primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glucose, lipids, and adverse events. From initially screened 24 articles, data from 3 RCTs (3591 patients) that fulfilled all criteria was analzsed. HbA1c was significantly lower with standard-dose (1 mg/d) [MD-0.86% (95%CI:-1.11--0.61); P < 0.01; I2 = 87%] and high-dose (1.5-2 mg/d) [MD-0.97%(95%CI:-1.03--0.90); P < 0.01; I2 = 19%] rivoglitazone compared to placebo. When compared to pioglitazone (30-45 mg/d), HbA1c lowering was comparable with standard-dose [MD 0.05%(95%CI:-0.01 - 0.11); P = 0.08; I2 = 11%], but superior with high-dose [MD -0.11%(95%CI:-0.18- -0.04); P < 0.01; I2 = 0%] rivoglitazone. Triglycerides were significantly lower with standard-dose [MD-17.95 mg/dl (95%CI:-34.23--1.66); P = 0.03; I2 = 0%] and high-dose [MD-40.41 mg/dl (95%CI:-72.90- -7.93);P = 0.01;I2 = 71%] rivoglitazone compared to placebo. Adiponectin significantly improved with standard-dose [MD 7.94 ng/ml (95%CI: 5.48-10.39); P < 0.01;I2 = 98%] and high-dose [MD 13.82 ng/ml (95%CI: 8.16-19.48); P < 0.01; I2 = 100%] rivoglitazone compared to placebo. hsCRP was significantly lower with standard-dose [MD -1.00 mg/L (95% CI: -1.20 - -0.80); P < 0.01; I2 = 6%] and high-dose [MD -1.50 mg/L (95%CI:-1.59- -1.40); P < 0.01; I2 = 0%] rivoglitazone compared to placebo. Treatment-emergent adverse events with standard-dose [Risk ratio (RR) 1.16 (95%CI: 0.84 -1.60); P = 0.38; I2 = 0%] and high-dose [RR1.34 (95%CI: 0.99-1.83); P = 0.06; I2 = 0%] rivoglitazone was comparable to placebo. Severe adverse events with standard-dose [RR1.88 (95%CI: 0.69-5.12);P = 0.22;I2 = 0%] and high-dose [RR 1.27 (95% CI: 0.45 - 3.59); P = 0.68; I2 = 0%] rivoglitazone was comparable to placebo. This meta-analysis highlights the good glycaemic efficacy and safety of both standard and high-dose rivoglitazone, and appears to be better than lobeglitazone in T2DM.
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Meta-analysis studying the role of verapamil in improving C-peptide in people with recent-onset type-1 diabetes (T1DM) has not been conducted to date. We undertook this meta-analysis to address this knowledge gap. Electronic databases were systematically reviewed for RCTs having individuals with T1DM receiving verapamil in the treatment arm and placebo in the control arm over the standard of care. The primary outcome was to evaluate changes in the C-peptide area under the curve (AUC) at a one-year follow-up. Secondary outcomes were to assess alterations in C-peptide AUC, glycated hemoglobin (HbA1c), blood pressure, heart rate, and side effects at different time intervals over a one-year follow-up. From the initially screened 27 articles, data from two RCTs (112 patients) satisfied the inclusion criteria and were analyzed. Compared to placebo, C-peptide AUC in individuals receiving verapamil was not different at three months [MD 0.17 nmol/L (95%CI: -0.05-0.38); P = 0.13; I2 = 86%] but significantly higher at 1-year [MD 0.27 nmol/L (95%CI: 0.19-0.35); P < 0.01; I2 = 12%]. The verapamil arm showed similar changes in HbA1C at three months [MD 0.23% (95%CI: -0.43-0.90); P = 0.49; I2 = 88%] and 1-year [MD 0.18% (95% CI: -0.74 - 1.10); P = 0.70; I2 = 89%] compared to placebo. Occurrence of treatment-emergent adverse events [Risk ratio (RR) 1.90 (95%CI: 0.52-6.91); P = 0.33; I2 = 63%], serious adverse events [RR 1.40 (95%CI: 0.50-3.93); P = 0.53], constipation [RR4.11 (95%CI: 0.93-18.13); P = 0.06; I2 = 0%], headache [RR0.48 (95%CI: 0.16-1.43); P = 0.19; I2 = 0%], severe hypoglycemia [RR 0.87 (95%CI: 0.06 - 13.51); P = 0.92] were comparable across groups. Verapamil was well tolerated, and its use over one year was associated with significant improvements in C-peptide AUC though the HbA1c remained unchanged.
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BACKGROUND: French national health care insurance system database has suggested 1-3 years use of glucagon like peptide-1 receptor agonists (GLP1RA) (exenatide, liraglutide and dulaglutide) may be linked with increased occurrence of thyroid cancer. Similar data on semaglutide is not-available. Hence, we undertook this systematic review to look at the safety of semaglutide focussing on different cancers. METHODS: Databases were searched for randomized controlled trials (RCTs) and real-world studies involving patients receiving semaglutide in the intervention-arm. Primary outcome was to evaluate the occurrence of pancreatic and thyroid cancers. Secondary outcomes were to the evaluate occurrence of any other malignancies or severe adverse-events. RESULTS: Data from 37 RCTs and 19 real-world studies having 16,839 patients in placebo-control group, 16,550 patients in active-control group and 13,330 patients in real-world studies were analysed. Compared to placebo, occurrence of pancreatic cancer [OR 0.25 (95%CI: 0.03-2.24); P = 0.21], thyroid cancer [OR 2.04 (95%CI: 0.33-12.61); P = 0.44; I2 = 0%] and all neoplasms (benign, malignant and otherwise unspecified) [OR 0.95 (95%CI:0.62-1.45); P = 0.82; I2 = 0%] was similar in the semaglutide group. Compared to active controls, occurrence of pancreatic cancer [OR 0.40 (95%CI:0.09-1.87); P = 0.26; I2 = 0%], thyroid cancer [OR 1.19 (95%CI:0.15-9.66); P = 0.87; I2 = 0%] and all neoplasms (benign, malignant and otherwise unspecified) [OR 0.91 (95% CI: 0.44-1.89); P = 0.79; I2 = 0%] were similar in the semaglutide group. Real-world data analysis revealed single case each of pancreatic cancer and B-cell lymphoma. CONCLUSION: Semaglutide use in RCTs and real-world studies was not associated with an increased risk of any types of cancer, and this conclusion is supported by a high grade of evidence.
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BACKGROUND & AIMS: No meta-analysis is available analysing the role of luseogliflozin in type-2 diabetes. We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for RCTs involving diabetes patients receiving luseogliflozin in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glucose, blood pressure, weight, lipids, and adverse events. RESULTS: From initially screened 151 articles, data from 10 RCTs involving 1304 patients was analysed. Individuals receiving luseogliflozin 2.5 mg/d had a significantly lower HbA1c [MD -0.76% (95% CI: 1.01 to -0.51); P < 0.01; I2 = 83%], fasting glucose [MD -26.69 mg/dl (95% CI: 35.41 to -17.96); P < 0.01; I2 = 80%], systolic blood pressure [MD -4.19 mm Hg (95% CI: 6.31 to -2.07); P < 0.01; I2 = 0%], body-weight [MD -1.61 kg (95% CI: 3.14 to -0.08); P = 0.04; I2 = 0%], triglycerides PCG [MD -12.60 mg/dl (95% CI: 24.25 to -0.95); P = 0.03; I2 = 0%], uric acid [MD -0.48 mg/dl (95% CI: 0.73 to -0.23); P < 0.01; I2 = 49%] and alanine aminotransferase [MD -4.11 IU/L (95% CI: 6.12 to -2.10); P < 0.01; I2 = 0%] compared to placebo. Occurrence of treatment-emergent adverse-events [RR 0.93 (95% CI: 0.72-1.20); P = 0.58; I2 = 0%], severe adverse-events [RR 1.19 (95% CI: 0.40-3.55); P = 0.76; I2 = 0%], hypoglycaemia [RR 1.56 (95% CI: 0.85-2.85); P = 0.15; I2 = 0%] and genital infections [RR 1.42 (95% CI: 0.48-4.18); P = 0.53; I2 = 0%] were not increased with luseogliflozin. Cardiovascular outcome trials are lacking and are urgently required. CONCLUSION: Luseogliflozin has good glycaemic and non-glycaemic benefits similar to other SGLT2 inhibitors and is well tolerated.
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Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Humanos , Hipoglucemiantes/uso terapéutico , Hemoglobina Glucada , Diabetes Mellitus Tipo 2/complicaciones , Glucosa , GlucemiaRESUMEN
Plant growth promoting rhizobacteria (PGPR) communicate with plants through roots. The molecular mechanism by which plants and PGPR respond to each other is not very well known. In the current study, we did RNA sequence analysis of Brachypodium distachyon Bd21-3 roots inoculated with PGPR, Bacillus velezensis strain B26. From our list of differentially expressed genes, we concentrated on transcripts that have a high possibility of participating in plant-PGPR interaction. Transcripts associated to the hormone signalling pathway were differentially expressed. We identified the upregulation of various transcripts linked to ion transporters. Reduction in expression of defense signalling genes indicated that B26 suppresses the plant defense mechanisms to begin successful interaction with roots. Transcripts associated with lignin branch of the phenylpropanoid pathway were upregulated as well, leading to more accumulation of lignin in the cell wall which enhances mechanical strength of plants. Overall, this study is an excellent resource for investigating associations between plant-PGPR interactions.
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Bacillus , Brachypodium , Brachypodium/genética , Lignina/metabolismo , Bacillus/genética , Bacillus/metabolismo , Desarrollo de la Planta , Raíces de Plantas/metabolismoRESUMEN
BACKGROUND AND AIMS: No meta-analysis has analysed the safety and efficacy of lobeglitazone in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for RCTs involving type-2 diabetes patients receiving lobeglitazone in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glucose, lipids and adverse events. RESULTS: From initially screened 65 articles, data from 4 RCTs (828 patients) which fulfilled all criteria was analysed. Over 24 weeks, when compared to sitagliptin 100 mg/d and half maximal pioglitazone dose (15 mg/d), lobeglitazone 0.5 mg/day had comparable impact on HbA1c [MD 0.03% (95%CI: 0.11-0.17); P = 0.65; I2 = 0%], fasting glucose [MD 1.47 mg/dl (95%CI: 4.66-7.60); P = 0.64; I2 = 0%], triglycerides [MD-9.96 mg/dl (95%CI: 43.55-23.62); P = 0.56; I2 = 81%], LDL-cholesterol [MD0.74 mg/dl (95%CI: 4.60-6.09); P = 0.79; I2 = 0%] and HDL-cholesterol [MD1.55 mg/dl (95%CI: 3.72-6.82); P = 0.56]. Occurrence of treatment-emergent adverse events (AEs) [RR 1.07 (95% CI:0.78-1.47); P = 0.67; I2 = 0%] and severe AEs [RR 1.05(95%CI: 0.42-2.65); P = 0.91; I2 = 0%] were similar. Edema and weight gain were significantly higher with lobeglitazone compared to controls [RR 2.58 (95%CI: 1.08-6.17); P = 0.03; I2 = 0%]. Lobeglitazone 0.5 mg/d compared to half-maximal pioglitazone (15 mg/d), had similar edema and weight gain [RR 1.65 95% CI: 0.78-1.47)]. BMD percent changes at neck of femur was comparable in both groups [MD 0.07% (95%CI: 0.19-0.33); P = 0.60; I2 = 91%]. Low dose lobeglitazone (0.25 mg/d) was inferior to high dose lobeglitazone (0.5 mg/d) with regards to glycaemic efficacy with advantage of lower weight gain and edema. CONCLUSION: The current evidence makes lobeglitazone unlikely to replace pioglitazone as the preferred thiazolidinedione in T2DM.
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Diabetes Mellitus Tipo 2 , Tiazolidinedionas , Humanos , Hipoglucemiantes/efectos adversos , Pioglitazona , Hemoglobina Glucada , Glucemia , Diabetes Mellitus Tipo 2/complicaciones , Tiazolidinedionas/efectos adversos , Aumento de Peso , ColesterolRESUMEN
BACKGROUND & AIMS: Glucokinase has a critical role in regulating glucose homeostasis in humans, and has been a target for diabetes drug development since 1990s. Dorzagliatin is a novel allosteric dual glucokinase activator targeting both pancreatic and hepatic glucokinase. No meta-analysis has analysed the efficacy and safety of dorzagliatin in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for RCTs involving T2DM patients receiving dorzagliatin in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in blood glucose parameters, lipids, insulin-resistance and adverse events. RESULTS: From initially screened 17 articles, data from 3 RCTs (1333 patients) was analysed. Over 12-24 weeks use, dorzagliatin had significantly higher lowering of HbA1c [MD -0.66% (95%CI: -0.74 to -0.59); P < 0.01; I2 = 99%], fasting glucose [MD -32.03 mg/dl (95%CI: 45.12 to -18.94); P < 0.01; I2 = 100%], 2-h post-prandial glucose [MD -43.49 mg/dl (95%CI: -46.26 to -40.72); P < 0.01; I2 = 90%] along with greater number of patients achieving HbA1c<7% [OR 6.01 (95% CI: 2.50-14.46); P < 0.01; I2 = 83%], as compared to placebo. Dorzagliatin was associated with significant elevation of triglycerides [MD 0.43 mmol/L (95%CI:0.30-0.56); P < 0.01; I2 = 0%], greater occurrence of hyperlipidaemia [RR 1.52 (95% CI:1.05-2.18); P = 0.03; I2 = 0%], and increase in body-weight [MD 0.40 kg (95%CI:0.06-0.75); P = 0.03; I2 = 0%], compared to placebo. The occurrence of total-adverse-events [RR 1.43 (95%CI:1.11-1.83); P < 0.01; I2 = 0%] but not severe adverse-events [RR 0.92 (95%CI:0.54-1.57); P = 0.76; I2 = 0%] was significantly higher with dorzagliatin. CONCLUSION: Dorzagliatin has good glycaemic efficacy and well tolerated over 6-months use. Mild increase in body-weight, serum triglycerides and overall adverse events remain issues of concern warranting further evaluation in longer clinical trials with active controls.
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Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Humanos , Glucemia/análisis , Glucoquinasa/metabolismo , Hemoglobina Glucada , Hipoglucemiantes/uso terapéuticoRESUMEN
BACKGROUND: No meta-analysis has analysed efficacy and safety of fast-acting aspart insulin (FIAsp) with insulin pump in type 1 diabetes mellitus (T1DM). METHODS: Electronic databases were searched for randomised controlled trials (RCTs) involving T1DM patients on insulin pump receiving FIAsp in intervention arm, and placebo/active comparator insulin in control arm. Primary outcome was to evaluate changes in 1- and 2-hour post-prandial glucose (1hPPG and 2hPPG). Secondary outcomes were to evaluate alterations in percentage time with blood glucose <3.9 mmol/L (hypoglycaemia), time in range (TIR) blood glucose 3.9 to 10 mmol/L, insulin requirements and adverse events. RESULTS: Data from four RCTs involving 640 patients was analysed. FIAsp use in insulin pump was associated with significantly greater lowering of 1hPPG (mean difference [MD], -1.35 mmol/L; 95% confidence interval [CI], -1.72 to -0.98; P<0.01; I2=63%) and 2hPPG (MD, -1.19 mmol/L; 95% CI, -1.38 to -1.00; P<0.01; I2=0%) as compared to controls. TIR was comparable among groups (MD, 1.06%; 95% CI, -3.84 to 5.96; P=0.67; I2=70%). Duration of blood glucose <3.9 mmol/L was lower in FIAsp group, approaching significance (MD, -0.91%; 95% CI, -1.84 to 0.03; P=0.06; I2=0%). Total hypoglycaemic episodes (risk ratio [RR], 1.35; 95% CI, 0.55 to 3.31; P=0.51; I2=0%), severe hypoglycaemia (RR, 2.26; 95% CI, 0.77 to 6.66; P=0.14), infusion site reactions (RR, 1.35; 95% CI, 0.63 to 2.93; P=0.77; I2=0%), and treatment-emergent adverse events (RR, 1.13; 95% CI, 0.80 to 1.60; P=0.50; I2=0%) were comparable. CONCLUSION: FIAsp use in insulin pump is associated with better post-prandial glycaemic control with no increased hypoglycaemia or glycaemic variability.
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Diabetes Mellitus Tipo 1 , Hipoglucemia , Humanos , Glucemia , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemia/inducido químicamente , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Insulina Aspart/uso terapéuticoRESUMEN
Background: Enhanced external counter-pulsation (EECP) therapy is approved for refractory angina in coronary artery disease (CAD). EECP is being explored as a treatment modality in type 2 diabetes mellitus (T2DM). Methods: The Embase, Web of Science, Cochrane Library, MEDLINE (PubMed), ClinicaltTrials. gov, CNKI database, Clinical Trials Registry-india (CTRI), and Google Scholar databases were searched for randomized controlled trials (RCTs) involving patients receiving EECP therapy in the intervention arm. The primary outcome was the changes in glycated haemoglobin (HbA1c). The secondary outcomes were the changes in blood glucose parameters, inflammatory markers and any adverse events. Results: Data from 3 RCTs involving 71 people with T2DM/prediabetes was analysed to find out the impact of EECP therapy compared with placebo. As compared with placebo, patients receiving EECP had significantly lower HbA1C immediately after completion of therapy (mean difference [MD] -0.70%, 95% confidence interval (CI) -0.95. -0.45;p<0.00001), at 2-4 weeks post completion of therapy (MD -1.04%, 95%CI -1.32. -0.77; p<0.00001) and 7-12 weeks after therapy completion (MD -0.98%, 95% CI -1.22, -0.74; p<0.00001). EECP therapy was well tolerated without any increased side effects (risk ratio 2.36, 95% CI 0.11-52.41; p=0.59. Conclusion: EECP therapy is effective in blood glucose and pressure lowering over at least 7-12 weeks of therapy completion. Blood glucose and pressure should be monitored with suitable modulation of drug doses to prevent hypoglycaemia and hypotension in patients with angina undergoing EECP therapy. The PROSPERO registration number is CRD42023434533.
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Background: Mechanistically, subcutaneous ultra-rapid lispro (URLi) is faster than lispro. Whether this translates into a better post-prandial glucose (PPG) and glycemic control in type-1 diabetes (T1DM) and type-2 diabetes (T2DM) is unclear. Hence, we undertook this meta-analysis. Methods: Databases were searched for randomized controlled trials (RCTs) involving patients with T1DM/T2DM receiving URLi in intervention-arm, and placebo/prandial insulin as control. The primary outcome was a change in PPG. Secondary outcomes were alterations in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), time in range (TIR), and adverse events. Results: Data from six RCTs (3687 patients) were analyzed. Lispro was the control arm in all RCTs. T1DM patients receiving mealtime URLi had lower HbA1c [mean difference (MD) -0.07%; 95% confidence interval (CI): -0.12 to - 0.01; P = 0.02; I2 = 42%] and 1-h PPG [MD - 1.18 mmol/L; 95% CI: -1.91 to - 0.44; P = 0.002; I2 = 100%]. T1DM patients receiving post-meal URLi had comparable HbA1c [MD 0.07%; 95% CI: -0.01 to 0.15; P = 0.07; I2 = 55%] and 1-h PPG [MD 0.22 mmol/L; 95% CI: -0.80 to 1.24; P = 0.67; I2 = 100%). T1DM patients on pumps receiving URLi had comparable TIR [MD 1.70; 95% CI: -0.29 to 3.69; P = 0.09; I2 = 98%], lower time in blood glucose <3 mmol/L with increased infusion-set reactions. T2DM patients receiving mealtime URLi had lower 1-h PPG [MD - 0.66 mmol/L; 95% CI: -0.69 to - 0.63; P < 0.00001; I2 = 0%(LH), 2-h-PPG [MD - 0.96 mmol/L; 95% CI: -1.00 to - 0.92; P < 0.00001; I2 = 0%], higher FPG [MD 0.18 mmol/L; 95% CI: 0.11-0.24; P < 0.00001; I2 = 20%], and higher HbA1c [MD 0.07%; 95% CI: -0.06 to 0.08; P < 0.00001; I2 = 0%]. Conclusion: Pre-meal URLi is better than lispro with regard to PPG control. Post-meal URLi is as good as lispro for PPG control. Post-meal URLi is inferior to pre-meal URLi for PPG control.
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Background: Data are scant on use of finerenone in diabetic kidney disease (DKD). We undertook this meta-analysis to address this knowledge gap. Methods: Electronic databases were searched for randomized controlled trials (RCTs) involving diabetes patients receiving finerenone compared to controls. The primary outcome was changes in urine albumin-creatinine ratio (UACR). Secondary outcomes were time to kidney failure (decline in GFR by >40% from baseline over 4 weeks), time to end-stage kidney disease, hospitalization for any cause, death and adverse events reported. Results: From initially screened 79 articles, data from 7 RCTs involving 13,783 patients were analyzed (3 in active control group [ACG] defined as having eplerenone/spironolactone as active comparator; 4 in passive control group [PCG] defined as having placebo as controls). Patients receiving finerenone had greater percentage lowering of UACR from baseline as compared to PCG [MD23.82% (95%CI: -24.87 to -22.77); P < 0.01; I 2 = 96%] at 90 days, after 2 years [MD 37.9% (95%CI: -38.09 to -37.71); P < 0.01] and 4 years [MD 25.20%(95%CI: -25.63 to -24.77);P < 0.01] of treatment. Patients receiving finerenone has lower chance of >40% decline in GFR (OR 0.83 [95%CI: 0.75 to 0.92];P < 0.01; I 2 = 0%). Patients receiving finerenone had lower occurrence of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure, as compared to placebo/eplerenone (OR0.86 [95%CI: 0.78 to 0.95]; P = 0.003; I 2 = 0%). TAEs was similar (RR0.97 [95%CI: 0.88-1.07]; P = 0.56; I 2 = 0%), but SAEs significantly lower (RR0.91 [95%CI: 0.84 to 0.97]; P < 0.01; I 2 = 0%) in finerenone-group compared to controls. Conclusion: This meta-analysis provides reassuring data on beneficial impact of finerenone in reducing UACR and GFR decline as compared to placebo. We still lack head-to-head comparison of renal outcomes of finerenone vs eplerenone/spironolactone in DKD.
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BACKGROUND AND AIMS: No meta-analysis has analysed efficacy and safety of semaglutide in metabolic-dysfunction associated fatty-liver disease (MAFLD). METHODS: Electronic databases were searched for RCTs involving people with MAFLD and/or type-2 diabetes (T2DM) receiving semaglutide. Primary outcome was to evaluate changes in alanine aminotransferase (ALT). Secondary outcomes were to evaluate alterations in other measures of NAFLD, glycaemia, lipids and adverse-events. RESULTS: Data from 4 RCTs (2115 patients) was analysed. A greater lowering with injectable semaglutide 0.4mg/0.5 mg once weekly was seen with regards to ALT [MD -3.89U/L (95%CI: -5.41 to -2.36); P < 0.01; I2 = 0%; 2050 patients], liver stiffness (fibroscan®) [MD -3.19 kPa (95%CI: -3.26 to -3.12); P < 0.01; 162 patients], steatosis [MD -13.40 dB/m (95%CI: 20.56 to -6.24); P < 0.01; 162 patients], triglycerides [MD -21.43 mg/dl (95% CI: 41.63 to -1.23); P = 0.04; I2 = 99%; 2050 patients], total cholesterol [MD -5.53 mg/dl (95% CI: -8.45 to -2.61); P < 0.01; I2 = 0%; 1888 patients], LDL-cholesterol [MD -3.55 mg/dl (95% CI: -5.87 to -1.23); P < 0.01; I2 = 0%; 1888 patients], percent-weight [MD -8.99% (95%CI: -14.64 to -3.34); P = 0.002; I2 = 100%; 2115 patient] and HbA1c [MD -0.77% (95%CI: 1.10 to -0.45); P = 0.002; I2 = 100%; 2115 patients]. Number of patients inadequate to comment on histopathologic measures of MAFLD. Occurrence of treatment-emergent adverse-events [RR 2.31 (95% CI: 0.76-7.06); P = 0.14; I2 = 82%] and severe adverse events [RR 1.07 (95%CI: 0.69-1.65); P = 0.77; I2 = 33%] were comparable. Adverse-events leading to trial discontinuation [RR 2.37 (95% CI: 1.33-4.22); P = 0.003; I2 = 24%], diarrhea [RR 2.05 (95%CI: 1.17-3.60); P = 0.01; I2 = 66%], nausea [RR 4.98 (95%CI: 3.23-7.67); P < 0.001; I2 = 0%] and vomiting [RR 3.90 (95%CI: 1.75-8.68); P < 0.01; I2 = 54%] were higher with semaglutide. CONCLUSION: This meta-analysis provides reassuring data on efficacy of low dose semaglutide injections in improving ALT and certain radiologic features in MAFLD. Current conclusions are limited by small number of patients evaluated. Urgent need remains for larger studies focussing on liver biopsy.