-
Frontiers in Endocrinology 2023The safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons. (Comparative Study)
Comparative Study Meta-Analysis
Comparative safety of different sodium-glucose transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUNDS
The safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons.
METHODS
This network meta-analysis (NMA) was performed to compare the safety of nine SGLT-2 inhibitors in patients with type 2 diabetes (T2DM). PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for studies published in English before August 30, 2022. Published and unpublished randomized controlled trials (RCTs) comparing the safety of individual SGLT-2 inhibitors in patients with T2DM were included. A Bayesian NMA with random effects model was applied. Subgroup and sensitivity analyses were performed. The quality of the evidence was evaluated using the Confidence in Network Meta-Analysis framework.
RESULTS
Nine SGLT-2 inhibitors were evaluated in 113 RCTs (12 registries) involving 105,293 adult patients. Reproductive tract infections (RTIs) were reported in 1,967 (4.51%) and 276 (1.01%) patients in the SGLT-2 inhibitor and placebo groups, respectively. Furthermore, pollakiuria was reported in 233 (2.66%) and 45 (0.84%) patients, respectively. Compared to placebo, a significantly higher risk of RTIs was observed with canagliflozin, ertugliflozin, empagliflozin, remogliflozin, dapagliflozin, and sotagliflozin, but not with luseogliflozin and ipragliflozin, regardless of gender. An increased risk of pollakiuria was observed with dapagliflozin [odds ratio (OR) 10.40, 95% confidence interval (CI) 1.60-157.94) and empagliflozin (OR 5.81, 95%CI 1.79-32.97). Remogliflozin (OR 6.45, 95%CI 2.18-27.79) and dapagliflozin (OR 1.33, 95%CI 1.10-1.62) were associated with an increased risk of urinary tract infections (UTIs). Instead, the included SGLT-2 inhibitors had a protective effect against acute kidney injury (AKI). No significant differences were found for hypovolemia, renal impairment or failure, fracture, diabetic ketoacidosis (DKA), amputation, and severe hypoglycemia between the SGLT-2 inhibitor and the placebo groups.
CONCLUSION
In patients with T2DM, dapagliflozin was associated with an increased risk of RTIs, pollakiuria, and UTIs. Empagliflozin increased the risk of RTIs and pollakiuria. Remogliflozin increased the risk of UTIs. None of the SGLT-2 inhibitors showed a significant difference from the placebo for hypovolemia, renal impairment or failure, fracture, DKA, amputation, and severe hypoglycemia. The findings guide the selection of SGLT-2 inhibitors for patients with T2DM based on the patient's profiles to maximize safety.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42022334644.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Fractures, Bone; Hypoglycemia; Hypovolemia; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37701900
DOI: 10.3389/fendo.2023.1238399 -
Age and Ageing Jan 2024Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in older or frail individuals remains unclear.
METHODS
We searched PubMed, Scopus, Web of Science, Cochrane CENTRA and Google Scholar and selected randomised controlled trials and observational studies comparing SGLT2Is versus placebo/other glucose-lowering agent for people with frailty or older individuals (>65 years) with T2D and heart failure (HF). Extracted data on the change in HbA1c % and safety outcomes were pooled in a random-effects meta-analysis model.
RESULTS
We included data from 20 studies (22 reports; N = 77,083 patients). SGLT2Is did not significantly reduce HbA1c level (mean difference -0.13, 95%CI: -0.41 to 0.14). SGLT2Is were associated with a significant reduction in the risk of all-cause mortality (risk ratio (RR) 0.81, 95%CI: -0.69 to 0.95), cardiac death (RR 0.80, 95%CI: -0.94 to 0.69) and hospitalisation for heart failure (HHF) (RR 0.69, 95%CI: 0.59-0.81). However, SGLT2Is did not demonstrate significant effect in reducing in the risk of macrovascular events (acute coronary syndrome or cerebral vascular occlusion), renal progression/composite renal endpoint, acute kidney injury, worsening HF, atrial fibrillation or diabetic ketoacidosis.
CONCLUSIONS
In older or frail patients with T2D and HF, SGLT2Is are consistently linked with a decrease in total mortality and the overall burden of cardiovascular (CV) events, including HHF events and cardiac death, but not protective for macrovascular death or renal events. Adverse events were more difficult to quantify but the risk of diabetic ketoacidosis or acute kidney injury was not significantly increase.
Topics: Humans; Aged; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Glycated Hemoglobin; Diabetic Ketoacidosis; Sodium-Glucose Transporter 2; Frail Elderly; Heart Failure; Death; Glucose; Sodium
PubMed: 38287703
DOI: 10.1093/ageing/afad254 -
Nutrients Aug 2023Alpha-lipoic acid (ALA) was found to improve the symptoms in patients with diabetic sensorimotor peripheral neuropathy (DSPN) by reducing oxidative stress and... (Meta-Analysis)
Meta-Analysis Review
Alpha-lipoic acid (ALA) was found to improve the symptoms in patients with diabetic sensorimotor peripheral neuropathy (DSPN) by reducing oxidative stress and ameliorating microcirculation. Our meta-analysis is aimed at evaluating the effects of oral-administered ALA versus a placebo in patients with DSPN and determining the optimal dosage for this treatment. We systematically reviewed randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to determine the efficacy of oral ALA for patients with DSPN. The primary outcome was total symptoms' score (TSS), and secondary outcomes were the neurological disability score (NDS), neuropathy impaired score (NIS), NIS-lower limb (NIS-LL), vibration perception threshold (VPT), nerve conduction study (NCS) results, and global satisfaction. A subgroup analysis of the ALA dosage (600, 1200, and 1800 mg/day) was also conducted. Ten RCTs (1242 patients) were included. ALA treatment produced favorable results for TSS (a dose-related trend was observed), NDS, and the global satisfaction score. For VAS, VPT, NIS-LL, and NCS results, ALA did not produce favorable results. ALA treatment had favorable effects on DSPN by reducing sensory symptoms, and it resulted in a dose-dependent response relative to the placebo for TSS and the global satisfaction score. The use of ALA to prevent neurological symptoms should be further researched.
Topics: Humans; Diabetic Neuropathies; Thioctic Acid; Administration, Oral; Databases, Factual; Lower Extremity; Diabetes Mellitus
PubMed: 37630823
DOI: 10.3390/nu15163634 -
The Journal of Clinical Endocrinology... Dec 2023Concomitant obesity is common among patients with type 1 diabetes mellitus (T1DM), yet adjunctive therapy options are scarce. (Meta-Analysis)
Meta-Analysis
CONTEXT
Concomitant obesity is common among patients with type 1 diabetes mellitus (T1DM), yet adjunctive therapy options are scarce.
OBJECTIVE
We assess the efficacy and adverse outcomes of glucagon-like peptide 1 (GLP-1) analogues when used as adjunctive therapy for T1DM.
METHOD
PubMed, EMBASE, Cochrane Central, and Scopus databases were searched for randomized controlled trials up to December 2022. Efficacy outcomes were A1c level, body weight, and total daily insulin (TDI) after ≥12 weeks of GLP-1 therapy. We also assessed 12 different adverse outcomes. Subgroup analysis was done for newly diagnosed or C-peptide positive (C-pos) patients. We report the certainty of evidence based on the GRADE assessment tool.
RESULTS
A total of 24 studies using 4 different GLP-1 analogues with a total of 3377 patients were included. Liraglutide had the most substantial evidence with effect sizes on A1c (-0.09%/mg), weight (-2.2 kg/mg), and TDI (-4.32 IU/mg). Liraglutide dose was the greatest predictor of greater average weight loss and TDI decrease but was associated with higher odds of nausea (OR 6.5; 95% CI, 5.0-8.4) and ketosis (OR 1.8; 95% CI, 1.1-2.8). Odds of severe (OR 0.67; 95% CI, 0.43-1.04) or symptomatic hypoglycemia (OR 0.89; 95% CI, 0.53-1.51) were not significantly elevated. Among C-pos patients, greater A1c decrease (-0.51% vs -0.28%) but similar weight loss and TDI were seen. Effect sizes for exenatide were similar, but studies had higher risk of bias and safety data were sparse.
CONCLUSION
Our meta-analysis supports therapeutic benefits of liraglutide for patients with T1DM mainly for weight loss and insulin dose reduction. Newly diagnosed or C-pos patients do not appear to experience greater weight loss benefits.
Topics: Humans; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Hypoglycemic Agents; Insulin; Liraglutide; Venoms; Weight Loss
PubMed: 37561012
DOI: 10.1210/clinem/dgad471 -
Diabetes/metabolism Research and Reviews Mar 2024This publication represents a scheduled update of the 2019 guidelines of the International Working Group of the Diabetic Foot (IWGDF) addressing the use of systems to...
BACKGROUND
This publication represents a scheduled update of the 2019 guidelines of the International Working Group of the Diabetic Foot (IWGDF) addressing the use of systems to classify foot ulcers in people with diabetes in routine clinical practice. The guidelines are based on a systematic review of the available literature that identified 28 classifications addressed in 149 articles and, subsequently, expert opinion using the GRADE methodology.
METHODS
First, we have developed a list of classification systems considered as being potentially adequate for use in a clinical setting, through the summary of judgements for diagnostic tests, focussing on the usability, accuracy and reliability of each system to predict ulcer-related complications as well as use of resources. Second, we have determined, following group debate and consensus, which of them should be used in specific clinical scenarios. Following this process, in a person with diabetes and a foot ulcer we recommend: (a) for communication among healthcare professionals: to use the SINBAD (Site, Ischaemia, Bacterial infection, Area and Depth) system (first option) or consider using WIfI (Wound, Ischaemia, foot Infection) system (alternative option, when the required equipment and level of expertise is available and it is considered feasible) and in each case the individual variables that compose the systems should be described rather than a total score; (b) for predicting the outcome of an ulcer in a specific individual: no existing system could be recommended; (c) for characterising a person with an infected ulcer: the use of the IDSA/IWGDF classification (first option) or consider using the WIfI system (alternative option, when the required equipment and level of expertise is available and it is considered as feasible); (d) for characterising a person with peripheral artery disease: consider using the WIfI system as a means to stratify healing likelihood and amputation risk; (e) for the audit of outcome(s) of populations: the use of the SINBAD score.
CONCLUSIONS
For all recommendations made using GRADE, the certainty of evidence was judged, at best, as being low. Nevertheless, based on the rational application of current data this approach allowed the proposal of recommendations, which are likely to have clinical utility.
Topics: Humans; Diabetic Foot; Ulcer; Reproducibility of Results; Foot Ulcer; Ischemia; Diabetes Mellitus
PubMed: 37179483
DOI: 10.1002/dmrr.3648 -
Advances in Therapy Dec 2023A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a Treat & Extend (T&E) regime with intervals up to every 16 weeks (Q16W), relative to other therapies currently in use for treatment of diabetic macular oedema (DME). Of particular interest were anti-vascular endothelial growth factor (VEGF) therapies applied in flexible dosing regimens such as Pro re nata (PRN) and T&E, which are the mainstay in clinical practice.
METHODS
An SLR identifying randomised controlled trials (RCTs) published before August 2021 was conducted, followed by a Bayesian NMA comparing faricimab T&E treatment to aflibercept, ranibizumab, bevacizumab, dexamethasone and laser therapy. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), change in central subfield thickness (CST), injection frequency, ocular adverse events (AE) and all-cause discontinuation, all of which were evaluated at 12 months. Subgroup analyses including patients' naïve to anti-VEGF were conducted where feasible.
RESULTS
Twenty-six studies identified in the SLR were included in the NMA. Most importantly for decision making in clinical practise, faricimab T&E was associated with a statistically greater (95% credible intervals exclude zero) and clinically meaningful decrease in retinal thickness compared to all other flexible dosing regimens (greater retinal drying by 55-125 microns). Anatomical outcomes determine treatment efficacy and retreatment of patients. The NMA also showed a statistically greater increase in mean change in BCVA for faricimab T&E vs. flexible regimens using ranibizumab and bevacizumab (increase of 4.4-4.8 letters) as well as a numerical improvement vs. aflibercept PRN (two letters, 95% credible intervals including zero). Accordingly, the injection frequency was numerically lower versus other treatments using flexible dosing regimens (decrease by 0.92-1.43 injections). The analyses also indicated that the safety profile of faricimab T&E was comparable to those of ranibizumab and aflibercept, which have well-established safety profiles, with similar results for the number of all-cause discontinuations.
CONCLUSION
Faricimab provides a new treatment option in DME with dual-pathway inhibition of VEGF and angiopoeitin-2 (Ang-2). To the authors' knowledge, this is the first indirect comparison of faricimab T&E in DME. The analyses indicate that faricimab T&E is associated with superior retinal drying along with numerically fewer injections compared to all other treatments given in flexible dosing regimens. It also showed superior visual acuity outcomes compared to ranibizumab and bevacizumab.
Topics: Humans; Angiogenesis Inhibitors; Bevacizumab; Diabetic Retinopathy; Intravitreal Injections; Macular Edema; Network Meta-Analysis; Ranibizumab; Vascular Endothelial Growth Factor A
PubMed: 37751021
DOI: 10.1007/s12325-023-02675-y -
Diabetes/metabolism Research and Reviews Mar 2024Principles of wound management, including debridement, wound bed preparation, and newer technologies involving alternation of wound physiology to facilitate healing, are...
AIMS
Principles of wound management, including debridement, wound bed preparation, and newer technologies involving alternation of wound physiology to facilitate healing, are of utmost importance when attempting to heal a chronic diabetes-related foot ulcer. However, the rising incidence and costs of diabetes-related foot ulcer management necessitate that interventions to enhance wound healing of chronic diabetes-related foot ulcers are supported by high-quality evidence of efficacy and cost effectiveness when used in conjunction with established aspects of gold-standard multidisciplinary care. This is the 2023 International Working Group on the Diabetic Foot (IWGDF) evidence-based guideline on wound healing interventions to promote healing of foot ulcers in persons with diabetes. It serves as an update of the 2019 IWGDF guideline.
MATERIALS AND METHODS
We followed the GRADE approach by devising clinical questions and important outcomes in the Patient-Intervention-Control-Outcome (PICO) format, undertaking a systematic review, developing summary of judgements tables, and writing recommendations and rationale for each question. Each recommendation is based on the evidence found in the systematic review and, using the GRADE summary of judgement items, including desirable and undesirable effects, certainty of evidence, patient values, resources required, cost effectiveness, equity, feasibility, and acceptability, we formulated recommendations that were agreed by the authors and reviewed by independent experts and stakeholders.
RESULTS
From the results of the systematic review and evidence-to-decision making process, we were able to make 29 separate recommendations. We made a number of conditional supportive recommendations for the use of interventions to improve healing of foot ulcers in people with diabetes. These include the use of sucrose octasulfate dressings, the use of negative pressure wound therapies for post-operative wounds, the use of placental-derived products, the use of the autologous leucocyte/platelet/fibrin patch, the use of topical oxygen therapy, and the use of hyperbaric oxygen. Although in all cases it was stressed that these should be used where best standard of care was not able to heal the wound alone and where resources were available for the interventions.
CONCLUSIONS
These wound healing recommendations should support improved outcomes for people with diabetes and ulcers of the foot, and we hope that widescale implementation will follow. However, although the certainty of much of the evidence on which to base the recommendations is improving, it remains poor overall. We encourage not more, but better quality trials including those with a health economic analysis, into this area.
Topics: Pregnancy; Female; Humans; Diabetic Foot; Placenta; Foot Ulcer; Wound Healing; Diabetes Mellitus
PubMed: 37232034
DOI: 10.1002/dmrr.3644 -
Diabetes/metabolism Research and Reviews Mar 2024This is the 2023 International Working Group on the Diabetic Foot guideline on the prevention of foot ulcers in persons with diabetes, which updates the 2019 guideline....
AIMS
This is the 2023 International Working Group on the Diabetic Foot guideline on the prevention of foot ulcers in persons with diabetes, which updates the 2019 guideline. This guideline is targeted at clinicians and other healthcare professionals.
MATERIALS AND METHODS
We followed the Grading of Recommendations, Assessment, Development and Evaluations methodology to devise clinical questions and critically important outcomes in the PICO format, to conduct a systematic review of the medical-scientific literature including, where appropriate, meta-analyses, and to write recommendations and their rationale. The recommendations are based on the quality of evidence found in the systematic review, expert opinion where (sufficient) evidence was not available, and a weighing of the desirable and undesirable effects of an intervention, as well as patient preferences, costs, equity, feasibility and applicability.
RESULTS
We recommend screening a person with diabetes at very low risk of foot ulceration annually for the loss of protective sensation and peripheral artery disease, and screening persons at higher risk at higher frequencies for additional risk factors. For preventing a foot ulcer, educate persons at-risk about appropriate foot self-care, educate not to walk without suitable foot protection, and treat any pre-ulcerative lesion on the foot. Educate moderate-to-high risk people with diabetes to wear properly fitting, accommodative, therapeutic footwear, and consider coaching them to monitor foot skin temperature. Prescribe therapeutic footwear that has a demonstrated plantar pressure relieving effect during walking, to help prevent plantar foot ulcer recurrence. Consider advising people at low-to-moderate risk to undertake a, preferably supervised, foot-ankle exercise programme to reduce ulcer risk factors, and consider communicating that a total increase in weight-bearing activity of 1000 steps/day is likely safe with regards to risk of ulceration. In people with non-rigid hammertoe with pre-ulcerative lesion, consider flexor tendon tenotomy. We suggest not to use a nerve decompression procedure to help prevent foot ulcers. Provide integrated foot care for moderate-to-high-risk people with diabetes to help prevent (recurrence of) ulceration.
CONCLUSIONS
These recommendations should help healthcare professionals to provide better care for persons with diabetes at risk of foot ulceration, to increase the number of ulcer-free days and reduce the patient and healthcare burden of diabetes-related foot disease.
Topics: Humans; Diabetic Foot; Foot Ulcer; Risk Factors; Evidence-Based Medicine; Diabetes Mellitus
PubMed: 37302121
DOI: 10.1002/dmrr.3651 -
Diabetes, Obesity & Metabolism Mar 2024To explore the safety and efficacy of subcutaneous semaglutide 2.4 mg, administered once a week in non-diabetic overweight or obese individuals. (Meta-Analysis)
Meta-Analysis
Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta-analysis including the 2-year STEP 5 trial.
AIM
To explore the safety and efficacy of subcutaneous semaglutide 2.4 mg, administered once a week in non-diabetic overweight or obese individuals.
METHODS
A thorough search was performed of various databases including PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrials.gov, CNKI and Wanfang from their inception up to April 11, 2023. Our aim was to identify randomized controlled trials (RCTs) that compared the efficacy of semaglutide administered once weekly with placebo in overweight or obese adults. Through a review of the literature, data were extracted from relevant studies and assessed for quality, and a meta-analysis was conducted using RevMan 5.4.1 software.
RESULTS
Six RCTs comprising 3962 overweight or obese individuals were identified. The findings indicated that, in comparison to the placebo group, semaglutide caused a significant and sustainable reduction in the percentage of body weight (BW; mean difference [MD]: -11.80% [95% confidence interval {CI} -12.93, -10.68]; P < 0.00001) as well as a decrease in absolute BW (MD: -12.2 kg [95% CI -13.3, -11.1]; P < 0.00001), body mass index (MD: -4.5 kg/m [95% CI -4.9, -4.1]; P < 0.00001) and waist circumference (MD:-9.4 cm [95% CI -10.1, -8.8]; P < 0.00001). Moreover, it achieved a higher proportion of patients who experienced weight loss exceeding 5%, 10%, 15% and 20%. Furthermore, semaglutide showed significant efficacy in controlling blood pressure, blood sugar levels, C-reactive protein levels, and lipid profiles. In terms of safety, the most common adverse effects following semaglutide treatment were gastrointestinal adverse reactions (risk ratio: 1.49 [95% CI 1.38, 1.60]; P < 0.00001), which were generally mild to moderate in severity and temporary.
CONCLUSION
In overweight or obese non-diabetic individuals, semaglutide had a remarkable and sustained weight loss effect that was well tolerated and safe.
Topics: Adult; Humans; Overweight; Hypoglycemic Agents; Obesity; Diabetes Mellitus; Weight Loss; Glucagon-Like Peptides
PubMed: 38016699
DOI: 10.1111/dom.15386 -
Liver International : Official Journal... Nov 2023Patients with some chronic liver diseases have increased risk of diabetes. Whether this is also the case for patients with autoimmune liver diseases is unknown. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Patients with some chronic liver diseases have increased risk of diabetes. Whether this is also the case for patients with autoimmune liver diseases is unknown. The study aimed to calculate risk and worldwide prevalence of diabetes in patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).
METHODS
We performed a case-control study using data from the United Kingdom Biobank (UKB) and compared frequency of type 1 diabetes (T1D) and type 2 diabetes (T2D) in AIH and PBC with age-, sex-, BMI- and ethnicity-matched controls. Next, we performed a systematic review and proportional meta-analysis searching PubMed, Embase, Cochrane Library and Web of Science (inception to 1 May 2022 [AIH]; 20 August 2022 [PBC]; 11 November 2022 [PSC]). The pooled prevalence of diabetes was calculated using an inverse method random effects model.
RESULTS
Three hundred twenty-eight AIH patients and 345 PBC patients were identified in UKB and risk of T1D and T2D significantly increased compared with matched controls. Our systematic search identified 6914 records including the UKB study. Of these, 77 studies were eligible for inclusion comprising 36 467, 39 924 and 4877 individuals with AIH, PBC and PSC, respectively. The pooled prevalence of T1D was 3.8% (2.6%-5.7%), 1.7% (0.9%-3.1%), 3.1% (1.9%-4.8%) and of T2D 14.8% (11.1%-19.5%), 18.1% (14.6%-22.2%), 6.3% (2.8%-13.3%) in patients with AIH, PBC and PSC, respectively.
CONCLUSIONS
Patients with autoimmune liver diseases have increased risk of diabetes. Increased awareness of diabetes risk in patients with autoimmune liver diseases is warranted.
Topics: Humans; Liver Cirrhosis, Biliary; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Case-Control Studies; Propensity Score; Liver Diseases; Autoimmune Diseases; Hepatitis, Autoimmune; Cholangitis, Sclerosing
PubMed: 37752719
DOI: 10.1111/liv.15720