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Reproductive Biology and Endocrinology... Jan 2023Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce gastrointestinal side effects.
OBJECTIVE
Inositols have long been debated as a potential alternative for metformin in treating PCOS. Therefore, the present systematic review aimed to evaluate the efficacy and safety of inositols in treating PCOS.
METHODS
The present systematic search was performed in CENTRAL, MEDLINE, and Embase from the inception until October 20th, 2021. Eligible randomized controlled trials (RCTs) included women diagnosed with PCOS and compared any inositols with metformin or placebo. Our primary outcome was cycle normalization, whereas secondary outcomes were body mass index (BMI), parameters of carbohydrate metabolism and clinical and laboratory hyperandrogenism. Results are reported as risk ratios or mean differences (MDs) with 95% confidence intervals (CIs).
RESULTS
Twenty-six RCTs were identified, including data of 1691 patients (806 inositol, 311 with placebo, and 509 metformin groups). In patients treated with inositols, the risk (CI: 1.13; 2.85) of having a regular menstrual cycle was found by 1.79 higher than in the case of placebo. Moreover, the inositols showed non-inferiority compared to metformin in this outcome. In the case of BMI (MD = -0.45; CI: -0.89; -0.02), free testosterone (MD = -0,41, CI: -0.69; -0.13), total testosterone (MD = -20.39, CI: -40.12; -0.66), androstenedione (MD = -0.69, CI: -1,16; -0.22), glucose (MD = -3.14; CI: -5.75; -0.54) levels and AUC insulin (MD = -2081.05, CI: -2745.32; -1416.78) inositol treatment induced greater decrease compared to placebo. Inositol increased sex-hormone-binding globulin significantly compared to placebo (MD = 32.06, CI:1.27; 62.85).
CONCLUSION
Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; metformin.
TRIAL REGISTRATION
PROSPERO registration number: CRD42021283275.
Topics: Female; Humans; Polycystic Ovary Syndrome; Inositol; Hypoglycemic Agents; Randomized Controlled Trials as Topic; Metformin; Testosterone; Insulins
PubMed: 36703143
DOI: 10.1186/s12958-023-01055-z -
Diabetologia Aug 2022Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) currently under review for marketing... (Meta-Analysis)
Meta-Analysis Review
AIMS/HYPOTHESIS
Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) currently under review for marketing approval. Individual trials have assessed the clinical profile of tirzepatide vs different comparators. We conducted a systematic review and meta-analysis to assess the efficacy and safety of tirzepatide for type 2 diabetes.
METHODS
We searched PubMed, Embase, Cochrane and ClinicalTrials.gov up until 27 October 2021 for randomised controlled trials with a duration of at least 12 weeks that compared once-weekly tirzepatide 5, 10 or 15 mg with placebo or other glucose-lowering drugs in adults with type 2 diabetes irrespective of their background glucose-lowering treatment. The primary outcome was change in HbA from baseline. Secondary efficacy outcomes included change in body weight, proportion of individuals reaching the HbA target of <53 mmol/mol (<7.0%), ≤48 mmol/mol (≤6.5%) or <39 mmol/mol (<5.7%), and proportion of individuals with body weight loss of at least 5%, 10% or 15%. Safety outcomes included hypoglycaemia, gastrointestinal adverse events, treatment discontinuation due to adverse events, serious adverse events, and mortality. We used version 2 of the Cochrane risk-of-bias tool for randomised trials to assess risk of bias for the primary outcome.
RESULTS
Seven trials (6609 participants) were included. A dose-dependent superiority in lowering HbA was evident with all three tirzepatide doses vs all comparators, with mean differences ranging from -17.71 mmol/mol (-1.62%) to -22.35 mmol/mol (-2.06%) vs placebo, -3.22 mmol/mol (-0.29%) to -10.06 mmol/mol (-0.92%) vs GLP-1 RAs, and -7.66 mmol/mol (-0.70%) to -12.02 mmol/mol (-1.09%) vs basal insulin regimens. Tirzepatide was more efficacious in reducing body weight; reductions vs GLP-1 RAs ranged from 1.68 kg with tirzepatide 5 mg to 7.16 kg with tirzepatide 15 mg. Incidence of hypoglycaemia with tirzepatide was similar vs placebo and lower vs basal insulin. Nausea was more frequent with tirzepatide vs placebo, especially with tirzepatide 15 mg (OR 5.60 [95% CI 3.12, 10.06]), associated with higher incidence of vomiting (OR 5.50 [95% CI 2.40, 12.59]) and diarrhoea (OR 3.31 [95% CI 1.40, 7.85]). Odds of gastrointestinal events were similar between tirzepatide and GLP-1 RAs, except for diarrhoea with tirzepatide 10 mg (OR 1.51 [95% CI 1.07, 2.15]). Tirzepatide 15 mg led to higher discontinuation rate of study medication due to adverse events regardless of comparator, while all tirzepatide doses were safe in terms of serious adverse events and mortality.
CONCLUSIONS/INTERPRETATION
A dose-dependent superiority on glycaemic efficacy and body weight reduction was evident with tirzepatide vs placebo, GLP-1 RAs and basal insulin. Tirzepatide did not increase the odds of hypoglycaemia but was associated with increased incidence of gastrointestinal adverse events. Study limitations include presence of statistical heterogeneity in the meta-analyses for change in HbA and body weight, assessment of risk of bias solely for the primary outcome, and generalisation of findings mainly to individuals who are overweight or obese and already on metformin-based background therapy. PROSPERO registration no. CRD42021283449.
Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diarrhea; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulins; Treatment Outcome
PubMed: 35579691
DOI: 10.1007/s00125-022-05715-4 -
Journal of Diabetes Research 2019To compare the efficacy and safety of metformin, glyburide, and insulin in treating gestational diabetes mellitus (GDM), a meta-analysis of randomized controlled trials... (Meta-Analysis)
Meta-Analysis
To compare the efficacy and safety of metformin, glyburide, and insulin in treating gestational diabetes mellitus (GDM), a meta-analysis of randomized controlled trials (RCTs) was conducted. PubMed, Embase, CINAHL, Web of Science, and Cochrane Library to November 13, 2018, were searched for RCT adjusted estimates of the efficacy and safety of metformin, glyburide, and insulin treatments in GDM patients. There were 41 studies involving 7703 GDM patients which were included in this meta-analysis; 12 primary outcomes and 24 secondary outcomes were detected and analyzed. Compared with metformin, insulin had a significant increase in the risk of preeclampsia (RR, 0.57; 95% CI, 0.45 to 0.72; < 0.001), NICU admission (RR, 0.75; 95% CI, 0.64 to 0.87; < 0.001), neonatal hypoglycemia (RR, 0.57; 95% CI, 0.49 to 0.66; < 0.001), and macrosomia (RR, 0.68; 95% CI, 0.55 to 0.86; < 0.05). To the outcomes of birth weight and gestational age at delivery, insulin had a significant increase when compared with metformin (MD, 114.48; 95% CI, 37.32 to 191.64; < 0.01; MD, 0.23; 95% CI, 0.12 to 0.34; < 0.001; respectively). Of the two groups between glyburide and metformin, metformin had lower gestational weight gain compared with glyburide (MD, 1.67; 95% CI, 0.26 to 3.07; < 0.05). Glyburide had a higher risk of neonatal hypoglycemia compared with insulin (RR, 1.76; 95% CI, 1.32 to 2.36; < 0.001). This meta-analysis found that metformin could be a safe and effective treatment for GDM. However, clinicians should pay attention on the long-term offspring outcomes of the relative data with GDM patients treated with metformin. Compared with insulin, glyburide had a higher increase of neonatal hypoglycemia. The use of glyburide in pregnancy for GDM women appears to be unclear.
Topics: Adult; Biomarkers; Blood Glucose; Diabetes, Gestational; Female; Glyburide; Humans; Hypoglycemic Agents; Insulin; Metformin; Patient Safety; Pregnancy; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome; Young Adult
PubMed: 31781670
DOI: 10.1155/2019/9804708 -
Pharmacological Research Sep 2021Obesity is frequently a comorbidity of type 2 diabetes. Even modest weight loss can significantly improve glucose homeostasis and lessen cardiometabolic risk factors in...
INTRODUCTION
Obesity is frequently a comorbidity of type 2 diabetes. Even modest weight loss can significantly improve glucose homeostasis and lessen cardiometabolic risk factors in patients with type 2 diabetes, but lifestyle-based weight loss strategies are not long-term effective. There is an increasing need to consider pharmacological approaches to assist weight loss in the so called diabesity syndrome. Aim of this review is to analyze the weight-loss effect of non-insulin glucose lowering drugs in patients with type 2 diabetes.
MATERIAL AND METHODS
A systematic analysis of the literature on the effect of non-insulin glucose lowering drugs on weight loss in patients with type 2 diabetes was performed. For each class of drugs, the following parameters were analyzed: kilograms lost on average, effect on body mass index and body composition.
RESULTS
Our results suggested that anti-diabetic drugs can be stratified into 3 groups based on their efficacy in weight loss: metformin, acarbose, empagliflozin and exenatide resulted in a in a mild weight loss (less than 3.2% of initial weight); canagliflozin, ertugliflozin, dapagliflozin and dulaglutide induces a moderate weight loss (between 3.2% and 5%); liraglutide, semaglutide and tirzepatide resulted in a strong weight loss (greater than 5%).
CONCLUSIONS
This study shows that new anti-diabetic drugs, particularly GLP1-RA and Tirzepatide, are the most effective in inducing weight loss in patients with type 2 diabetes. Interestingly, exenatide appears to be the only GLP1-RA that induces a mild weight loss.
Topics: Diabetes Mellitus, Type 2; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Obesity; Weight Loss
PubMed: 34302978
DOI: 10.1016/j.phrs.2021.105782 -
Kidney & Blood Pressure Research 2020The etiology of acute metabolic acidosis (aMA) is heterogeneous, and the consequences are potentially life-threatening. The aim of this article was to summarize the...
BACKGROUND
The etiology of acute metabolic acidosis (aMA) is heterogeneous, and the consequences are potentially life-threatening. The aim of this article was to summarize the causes and management of aMA from a clinician's perspective.
SUMMARY
We performed a systematic search on PubMed, applying the following search terms: "acute metabolic acidosis," "lactic acidosis," "metformin" AND "acidosis," "unbalanced solutions" AND "acidosis," "bicarbonate" AND "acidosis" AND "outcome," "acute metabolic acidosis" AND "management," and "acute metabolic acidosis" AND "renal replacement therapy (RRT)/dialysis." The literature search did not consider diabetic ketoacidosis at all. Lactic acidosis evolves from various conditions, either with or without systemic hypoxia. The incidence of metformin-associated aMA is actually quite low. Unbalanced electrolyte preparations can induce hyperchloremic aMA. The latter potentially worsens kidney-related outcome parameters. Nevertheless, prospective and controlled data are missing at the moment. Recently, bicarbonate has been shown to improve clinically relevant endpoints in the critically ill, even if higher pH values (>7.3) are targeted. New therapeutics for aMA control are under development, since bicarbonate treatment can induce serious side effects. Key Messages: aMA is a frequent and potentially life-threatening complication of various conditions. Lactic acidosis might occur even in the absence of systemic hypoxia. The incidence of metformin-associated aMA is comparably low. Unbalanced electrolyte solutions induce hyperchloremic aMA, which most likely worsens the renal prognosis of critically ill patients. Bicarbonate, although potentially deleterious due to increased carbon dioxide production with subsequent intracellular acidosis, improves kidney-related endpoints in the critically ill.
Topics: Acidosis; Acidosis, Lactic; Acute Disease; Animals; Bicarbonates; Disease Management; Electrolytes; Humans; Hypoglycemic Agents; Metformin
PubMed: 32663831
DOI: 10.1159/000507813 -
Clinical Oral Investigations May 2021This study aims to compare the treatment outcomes of periodontal intrabony defects by using platelet-rich fibrin (PRF) with other commonly utilized modalities. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study aims to compare the treatment outcomes of periodontal intrabony defects by using platelet-rich fibrin (PRF) with other commonly utilized modalities.
MATERIALS AND METHODS
The eligibility criteria comprised randomized controlled trials (RCTs) comparing the clinical outcomes of PRF with that of other modalities. Studies were classified into 10 categories as follows: (1) open flap debridement (OFD) alone versus OFD/PRF; (2) OFD/bone graft (OFD/BG) versus OFD/PRF; (3) OFD/BG versus OFD/BG/PRF; (4-6) OFD/barrier membrane (BM), OFD/PRP, or OFD/enamel matrix derivative (EMD) versus OFD/PRF; (7) OFD/EMD versus OFD/EMD/PRF; (8-10) OFD/PRF versus OFD/PRF/metformin, OFD/PRF/bisphosphonates, or OFD/PRF/statins. Weighted means and forest plots were calculated for probing depth (PD), clinical attachment level (CAL), and radiographic bone fill (RBF).
RESULTS
From 551 articles identified, 27 RCTs were included. The use of OFD/PRF statistically significantly reduced PD and improved CAL and RBF when compared to OFD. No clinically significant differences were reported when OFD/BG was compared to OFD/PRF. The addition of PRF to OFD/BG led to significant improvements in CAL and RBF. No differences were reported between any of the following groups (OFD/BM, OFD/PRP, and OFD/EMD) when compared to OFD/PRF. No improvements were also reported when PRF was added to OFD/EMD. The addition of all three of the following biomolecules (metformin, bisphosphonates, and statins) to OFD/PRF led to statistically significant improvements of PD, CAL, and RBF.
CONCLUSIONS
The use of PRF significantly improved clinical outcomes in intrabony defects when compared to OFD alone with similar levels being observed between OFD/BG and OFD/PRF. Future research geared toward better understanding potential ways to enhance the regenerative properties of PRF with various small biomolecules may prove valuable for future clinical applications. Future research investigating PRF at histological level is also needed.
CLINICAL RELEVANCE
The use of PRF in conjunction with OFD statistically significantly improved PD, CAL, and RBF values, yielding to comparable outcomes to OFD/BG. The combination of PRF with bone grafts or small biomolecules may offer certain clinical advantages, thus warranting further investigations.
Topics: Alveolar Bone Loss; Bone Transplantation; Guided Tissue Regeneration, Periodontal; Humans; Periodontal Attachment Loss; Platelet-Rich Fibrin; Surgical Flaps
PubMed: 33609186
DOI: 10.1007/s00784-021-03825-8 -
Hormone and Metabolic Research =... Jul 2022Aim To determine the antiobesity effect and safety of glucagon-like peptide-1 receptor agonist (GLP-1RA) including liraglutide, exenatide and semaglutide treatment in... (Meta-Analysis)
Meta-Analysis
Aim To determine the antiobesity effect and safety of glucagon-like peptide-1 receptor agonist (GLP-1RA) including liraglutide, exenatide and semaglutide treatment in overweight/obese patients without diabetes. The random-effect model was used to pool data extracted from included literatures. The weighted mean difference (WMD), odds ratio and 95% confidence interval (CI) were used to present the meta-analysis results (PROSPERO registration number: CRD 42020173199). The sources of intertrial heterogeneity, bias and the robustness of results were evaluated by subgroup analysis, sensitivity analysis and regression analysis, respectively. A total of 24 RCTs were recruited in the present analysis which included 5867 patients. The results showed that the treatment of overweight/obese patients without diabetes with GLP-1RAs including liraglutide, exenatide and semaglutide significantly achieved greater weight loss than placebo [WMD=-5.39, 95% CI (-6.82, -3.96)] and metformin [WMD=-5.46, 95% CI (-5.87, -5.05)]. The subgroup analysis showed that semaglutide displayed the most obvious antiobesity effect in terms of weight loss, the reduction of body mass index (BMI) and waist circumference (WC). However, GLP-1RAs treatments had more gastrointestinal adverse events (such as nausea and vomiting) than placebo and Met. The subgroup analysis also represented that semaglutide displayed the lowest risk of gastrointestinal adverse events among three kinds of GLP-1RAs. Our meta-analysis demonstrated that GLP-1RA had a superior antiobesity effect than placebo/Met in overweight/obese patients without diabetes in terms of body weight, BMI, and WC, especially for semaglutide, which had more obvious antiobesity effect and lower GI adverse events than liraglutide and exenatide.
Topics: Anti-Obesity Agents; Exenatide; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Humans; Hypoglycemic Agents; Liraglutide; Obesity; Weight Loss
PubMed: 35512849
DOI: 10.1055/a-1844-1176 -
Biomedicines Jan 2023Sarcopenia is a multifactorial condition related to the loss of muscle mass and strength due to aging, eating habits, physical inactivity, or even caused by another... (Review)
Review
Sarcopenia is a multifactorial condition related to the loss of muscle mass and strength due to aging, eating habits, physical inactivity, or even caused by another disease. Affected individuals have a higher risk of falls and may be associated with heart disease, respiratory diseases, cognitive impairment, and consequently an increased risk of hospitalization, in addition to causing an economic impact due to the high cost of care during the stay in hospitals. The standardization of appropriate treatment for patients with sarcopenia that could help reduce pathology-related morbidity is necessary. For these reasons, this study aimed to perform a systematic review of the role of nutrition and drugs that could ameliorate the health and quality of life of sarcopenic patients and PRISMA guidelines were followed. Lifestyle interventions have shown a profound impact on sarcopenia treatment but using supplements and different drugs can also impact skeletal muscle maintenance. Creatine, leucine, branched-chain amino acids, omega 3, and vitamin D can show benefits. Although with controversial results, medications such as Metformin, GLP-1, losartan, statin, growth hormone, and dipeptidyl peptidase 4 inhibitors have also been considered and can alter the sarcopenic's metabolic parameters, protect against cardiovascular diseases and outcomes, while protecting muscles.
PubMed: 36672642
DOI: 10.3390/biomedicines11010136 -
Acta Diabetologica May 2023To expand the evidence base for the clinical use of metformin, we conducted a meta-analysis of randomized controlled trials (RCTs) comparing the efficacy and safety of... (Meta-Analysis)
Meta-Analysis Review
Short-term neonatal outcomes in women with gestational diabetes treated using metformin versus insulin: a systematic review and meta-analysis of randomized controlled trials.
AIMS
To expand the evidence base for the clinical use of metformin, we conducted a meta-analysis of randomized controlled trials (RCTs) comparing the efficacy and safety of metformin versus insulin with respect to short-term neonatal outcomes.
METHODS
A comprehensive search of electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) was performed. Two reviewers extracted the data and calculated pooled estimates by use of a random-effects model. In total, 24 studies involving 4355 participants met the eligibility criteria and were included in the quantitative analyses.
RESULTS
Unlike insulin, metformin lowered neonatal birth weights (mean difference - 122.76 g; 95% confidence interval [CI] - 178.31, - 67.21; p < 0.0001), the risk of macrosomia (risk ratio [RR] 0.68; 95% CI 0.54, 0.86; p = 0.001), the incidence of neonatal intensive care unit admission (RR 0.73; 95% CI 0.61, 0.88; p = 0.0009), and the incidence of neonatal hypoglycemia (RR 0.65; 95% CI 0.52, 0.81; p = 0.0001). Subgroup analysis based on the maximum daily oral dose of metformin indicated that metformin-induced neonatal birth weight loss was independent of the oral dose.
CONCLUSIONS
Our meta-analysis provides further evidence that metformin is a safe oral antihyperglycemic drug and has some benefits over insulin when used for the treatment of gestational diabetes, without an increased risk of short-term neonatal adverse outcomes. Metformin may be particularly useful in women with gestational diabetes at high risk for neonatal hypoglycemia, women who want to limit maternal and fetal weight gain, and women with an inability to afford or use insulin safely.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Diabetes, Gestational; Metformin; Insulin; Hypoglycemic Agents; Randomized Controlled Trials as Topic; Hypoglycemia; Birth Weight; Weight Gain
PubMed: 36593391
DOI: 10.1007/s00592-022-02016-5 -
Diabetes & Metabolic Syndrome Oct 2022Metformin-treated type 2 diabetes mellitus (T2DM) patients are at higher risk of vitamin B deficiency and more severe neuropathy symptoms. There is still no guideline... (Review)
Review
The efficacy of vitamin B supplementation for treating vitamin B deficiency and peripheral neuropathy in metformin-treated type 2 diabetes mellitus patients: A systematic review.
BACKGROUND AND AIMS
Metformin-treated type 2 diabetes mellitus (T2DM) patients are at higher risk of vitamin B deficiency and more severe neuropathy symptoms. There is still no guideline suggesting vitamin B supplementation for this population. This study aimed to analyze the efficacy of vitamin B supplementation in this population.
METHOD
Studies reporting the efficacy of vitamin B supplementation in metformin-treated T2DM patients were systematically searched in PubMed, Cochrane, EBSCOHost, and Scopus following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Additional relevant studies were searched manually through citations. Study quality and risk of bias were assessed using suitable tools.
RESULTS
Seven clinical trials with a total of 506 participants were included. Using the Cochrane's Risk of Bias 2 tools for clinical trials, 4 studies were assessed to have high risk of bias and 3 studies had low risk of bias. There were 5 studies that measured changes in serum vitamin B level, all of which reported a statistically significant increase after supplementation. Significant reductions in homocysteine after supplementation were found in 2 studies. Its effect on neuropathy symptoms was still unclear, with 2 studies reporting a significant improvement and 1 study reporting no significant effect.
CONCLUSIONS
The results of this systematic review support the implementation of vitamin B supplementation for metformin-treated T2DM to prevent or treat vitamin B deficiency and neuropathy. More high-quality clinical studies are required to generate quantitative analysis and to encourage supplementation in available guidelines.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Vitamin B 12; Hypoglycemic Agents; Vitamin B 12 Deficiency; Peripheral Nervous System Diseases; Homocysteine; Dietary Supplements; Vitamins
PubMed: 36240684
DOI: 10.1016/j.dsx.2022.102634