-
Journal of Diabetes Feb 2023Patients with diabetes are more likely to suffer COVID-19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID-19 infection has proved... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with diabetes are more likely to suffer COVID-19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID-19 infection has proved challenging. In this study, we evaluate different noninsulin AGMs in patients with COVID-19.
METHODS
We searched Medline, Embase, Web of Science, and Cochrane on 24 January 2022. We used the following keywords (COVID-19) AND (diabetes mellitus) AND (antihyperglycemic agent). The inclusion criteria were studies reporting one or more of the outcomes. We excluded non-English articles, case reports, and literature reviews. Study outcomes were mortality, hospitalization, and intensive care unit (ICU) admission.
RESULTS
The use of metformin rather than other glucose-lowering medications was associated with statistically significant lower mortality (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.47, 0.77, p < .001). Dipeptidyl peptidase-4 inhibitor (DPP-4i) use was associated with statistically significantly higher hospitalization risk (RR: 1.44, 95% CI: 1.23, 1.68, p < .001) and higher risk of ICU admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, p < .02). There was a statistically significant decrease in hospitalization for SGLT-2i users vs nonusers (RR: 0.89, 95% CI: 0.84-0.95, p < .001). Glucagon-like peptide-1 receptor agonist (GLP-1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p < 0.001), ICU admission, and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69-0.89, p < .001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, p = .04).
CONCLUSIONS
AGM use was not associated with increased mortality. However, metformin and GLP-1RA use reduced mortality risk statistically significantly. DPP-4i use was associated with a statistically significant increase in the risk of hospitalization and admission to the ICU.
Topics: Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; COVID-19; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Glucagon-Like Peptide-1 Receptor
PubMed: 36690377
DOI: 10.1111/1753-0407.13359 -
Advanced Drug Delivery Reviews 2020The targeted delivery of therapeutic compounds to the brain is arguably the most significant open problem in drug delivery today. Nanoparticles (NPs) based on peptides...
The targeted delivery of therapeutic compounds to the brain is arguably the most significant open problem in drug delivery today. Nanoparticles (NPs) based on peptides and designed using the emerging principles of molecular engineering show enormous promise in overcoming many of the barriers to brain delivery faced by NPs made of more traditional materials. However, shortcomings in our understanding of peptide self-assembly and blood-brain barrier (BBB) transport mechanisms pose significant obstacles to progress in this area. In this review, we discuss recent work in engineering peptide nanocarriers for the delivery of therapeutic compounds to the brain: from synthesis, to self-assembly, to in vivo studies, as well as discussing in detail the biological hurdles that a nanoparticle must overcome to reach the brain.
Topics: Administration, Intranasal; Animals; Biological Transport; Blood-Brain Barrier; Brain; Drug Delivery Systems; Drug Implants; Humans; Nanoparticles; Peptides; Recombinant Proteins
PubMed: 33031897
DOI: 10.1016/j.addr.2020.10.001 -
Diabetes & Vascular Disease Research 2022While hemoglobin A1c (HbA1c) is commonly used to monitor therapy response in type 2 diabetes (T2D), GV is emerging as an essential additional metric for optimizing... (Meta-Analysis)
Meta-Analysis
While hemoglobin A1c (HbA1c) is commonly used to monitor therapy response in type 2 diabetes (T2D), GV is emerging as an essential additional metric for optimizing glycemic control. Our goal was to learn more about the impact of hypoglycemic agents on HbA1c levels and GV in patients with T2D. A systematic review and network meta-analysis (NMA) of randomized controlled trials were performed to assess the effects of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter (SGLT)-2 inhibitors, dipeptidyl peptidase (DPP)-4 inhibitors, sulfonylurea and thiazolidinediones on Mean Amplitude of Glycemic Excursions (MAGE) and HbA1c. Searches were performed using PubMed and EMBASE. A random-effect model was used in the NMA, and the surface under the cumulative ranking was used to rank comparisons. All studies were checked for quality according to their design and also for heterogeneity before inclusion in this NMA. The highest reduction in MAGE was achieved by GLP-1 RAs (SUCRA 0.83), followed by DPP-4 inhibitors (SUCRA: 0.72), and thiazolidinediones (SUCRA: 0.69). In terms of HbA1c reduction, GLP-1 RAs were the most effective (SUCRA 0.81), followed by DPP-4 inhibitors (SUCRA 0.72) and sulfonylurea (SUCRA 0.65). Our findings indicated that GLP-1 RAs have relatively high efficacy in terms of HbA1c and MAGE reduction when compared with other hypoglycemic agents and can thus have clinical application. Future studies with a larger sample size and appropriate subgroup analyses are warranted to completely understand the glycemic effects of these agents in various patients with T2D. The protocol for this systematic review was registered with the International Prospective Register of Systematic Reviews (CRD42021256363).
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Network Meta-Analysis; Sodium-Glucose Transporter 2 Inhibitors; Thiazolidinediones
PubMed: 35686694
DOI: 10.1177/14791641221106866 -
Frontiers in Endocrinology 2022This study aimed to assess the impact of different antidiabetic agents on individuals with diabetes and COVID-19. (Meta-Analysis)
Meta-Analysis
AIMS
This study aimed to assess the impact of different antidiabetic agents on individuals with diabetes and COVID-19.
METHODS
We searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to October 31, 2021 and included seven antidiabetic agents. The data were pooled traditional pairwise meta-analysis and Bayesian network meta-analysis.
RESULTS
The pairwise meta-analysis included 35 studies. Metformin (odds ratio (OR), 0.74; P=0.001), dipeptidyl peptidase-4 inhibitors (DPP4i) (OR, 0.88; P=0.04), sodium-glucose cotransporter-2 inhibitors (SGLT2i) (OR, 0.82; P=0.001), and glucagon-like peptide-1 receptor agonists (GLP1RA) (OR, 0.91; P=0.02) treatment were associated with lower COVID-19 mortality in individuals with diabetes compared to respective non-users. However, insulin treatment resulted in higher mortality (OR, 1.8; P=0.001). Mortality did not significantly differ in sulfonylurea (OR, 0.97; P=0.56) and thiazolidinediones (TZDs) (OR, 1.00; P=0.96) users. Furthermore, due to limited data, we analyzed five antidiabetic agents (metformin, DPP4i, sulfonylurea, insulin, and SGLT2i) and found no association between them and severe disease risk (all P>0.05). The Bayesian network meta-analysis included 18 studies. GLP1RA and SGLT2i had the highest first and second rank probability (67.3% and 62.5%, respectively). Insulin showed the maximum probability of ranking seventh (97.0%). Metformin had the third and fourth highest rank probability of 44.8% and 38.9%, respectively. Meanwhile, DPP4i had the fifth-highest rank probability of 42.4%, followed by sulfonylurea at 45.1%.
CONCLUSION
Metformin, DPP4i, SGLT2i, and GLP1RA treatments were highly possible to reduced COVID-19 mortality risk in individuals with diabetes, while insulin might be related to increased mortality risk. Sulfonylurea and TZDs treatments were not associated with mortality. None of the antidiabetic agents studied were associated with the risk of severe disease. Additionally, GLP1RA probably had the most significant protective effect against death, followed by SGLT2i and metformin.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42021288200).
Topics: Bayes Theorem; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hypoglycemic Agents; Insulin; Metformin; Network Meta-Analysis; Sodium-Glucose Transporter 2 Inhibitors; Thiazolidinediones; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 35692410
DOI: 10.3389/fendo.2022.895458 -
The Annals of Pharmacotherapy Sep 2022Assess evidence describing the effect of Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors on total daily insulin (TDI) requirements in insulin-dependent patients with... (Review)
Review
OBJECTIVE
Assess evidence describing the effect of Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors on total daily insulin (TDI) requirements in insulin-dependent patients with type 2 diabetes.
DATA SOURCES
A scoping review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Protocols and Scoping Reviews (PRISMA-ScR) guidelines. The search was conducted in PubMed; citation mapping was completed in Web of Science. Filters for human studies, English language, and a publication date, from January 1, 2005 to April 12, 2021, were applied.
STUDY SELECTION AND DATA EXTRACTION
Studies assessing insulin dose requirements with concurrent use of an SGLT2 inhibitor for patients with type 2 diabetes were included.
DATA SYNTHESIS
Sixteen studies were included and demonstrated that addition of an SGLT2 inhibitor typically reduced TDI requirements. Insulin reductions were often statistically significant, occurring in studies evaluating (1) within subjects who received SGLT2 inhibitors, and (2) between subjects receiving SGLT2 inhibitors versus placebo. Compared with placebo, insulin dose reduction ranged from -0.72 to -19.2 units. However, studies were relatively small, not designed to assess TDI change, and some utilized fixed dose insulin protocols or empiric insulin dose reductions.
CONCLUSIONS
Lowering insulin requirements may have benefits, such as decreased hypoglycemia risk, insulin resistance, and cost. Addition of an SGLT2 inhibitor may modestly reduce TDI requirements for patients with type 2 diabetes. Evidence indicating SGLT2 inhibitor use reduces TDI may lead to additional implementation in practice and inform future research. Further research is needed to clarify insulin type (i.e., basal or prandial) and degree of TDI reduction expected with addition of an SGLT2 inhibitor.
Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 35040335
DOI: 10.1177/10600280211071089 -
Current Therapeutic Research, Clinical... 2020The World Health Organization estimates that diabetes is the seventh leading cause of death. Uncontrolled diabetes may cause severe consequences such as cardiovascular... (Review)
Review
BACKGROUND
The World Health Organization estimates that diabetes is the seventh leading cause of death. Uncontrolled diabetes may cause severe consequences such as cardiovascular (CV) events (myocardial infarction, stroke, or CV mortality), lower-extremity amputations, and end-stage renal disease. Microvascular complications include retinopathy, autonomic and peripheral neuropathy, nephropathy, and diabetic ulcers. Major CV outcomes trials that were by the Food and Drug Administration for all new antihyperglycemia medications for patients at high risk for CV events were recently completed for all 4 US-marketed dipeptidyl peptidase-4 (DPP-4) inhibitors.
OBJECTIVE
To present a comprehensive review of the clinical trials that evaluate macrovascular and microvascular complications reported with DPP-4 inhibitors in patients with type 2 diabetes mellitus.
METHODS
In this review, we analyzed published articles in PubMed and Ovid databases between January 2008 and September 2019 that evaluated the effect of DPP-4 inhibitors on macrovascular and microvascular complications in patients with type 2 diabetes mellitus.
RESULTS
A total of 18 studies, which included randomized controlled trials and meta-analyses were assessed. Current evidence demonstrates that the addition of DPP-4 inhibitors to standard antihyperglycemic and CV risk reduction treatment has not shown CV benefit relative to placebo in contrast to recently published studies for other medications within the glucagon-like peptide 1 agonist and sodium-glucose co-transporter 2 inhibitor classes. Notably, the potential risk for heart failure hospitalizations may exist for saxagliptin, and this effect is not extrapolated as a class effect. Based on our review, DPP-4 inhibitors may not influence microvascular complications in patients with diabetes. However, some studies have shown that saxagliptin and linagliptin may slow down the progression of albuminuria in patients with type 2 diabetes mellitus. The overall quality of the studies included in this review was high due to the inclusion of randomized controlled trials and meta-analyses.
CONCLUSIONS
DPP-4 inhibitors were found to have a neutral effect on macrovascular and microvascular complications, with the exception of saxagliptin, which may increase the risk for heart failure hospitalizations.
PubMed: 32817765
DOI: 10.1016/j.curtheres.2020.100596 -
Diabetes, Obesity & Metabolism Aug 2022To conduct a systematic review and network meta-analysis to determine the comparative effectiveness of sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like... (Meta-Analysis)
Meta-Analysis
Comparative efficacy of novel antidiabetic drugs on cardiovascular and renal outcomes in patients with diabetic kidney disease: A systematic review and network meta-analysis.
AIMS
To conduct a systematic review and network meta-analysis to determine the comparative effectiveness of sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with diabetic kidney disease (DKD).
METHODS
Phase III or IV randomized, placebo-controlled trials evaluating SGLT2 inhibitors, GLP-1RAs or DPP-4 inhibitors in patients with DKD were identified from the MEDLINE database. The outcomes of interest were a kidney-specific composite outcome, kidney disease progression, major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF) and cardiovascular death. A network meta-analysis was conducted to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).
RESULTS
Sixteen trials representing a total of 46 292 patients were included. SGLT2 inhibitors significantly reduced the risk of the kidney-specific composite outcome by 26% compared to GLP-1RAs (HR 0.74, 95% CI 0.62-0.88) and by 36% compared to DPP-4 inhibitors (HR 0.64, 95% CI 0.52-0.79). The risk of MACE was significantly reduced with SGLT2 inhibitors (by 18%; HR 0.82, 95% CI 0.72-0.93), and with GLP-1RAs (by 18%; HR 0.82, 95% CI 0.69-0.96), compared to DPP-4 inhibitors. SGLT2 inhibitors significantly reduced the risk of HHF by 28% compared to GLP-1RAs (HR 0.72, 95% CI 0.56-0.92) and by 41% compared to DPP-4 inhibitors (HR 0.59, 95% CI 0.49-0.71).
CONCLUSIONS
A clear advantage was demonstrated by SGLT2 inhibitors in reducing the risks of CV and renal events in patients with DKD, compared to GLP-1RAs and DPP-4 inhibitors. We recommend that SGLT2 inhibitors be considered the treatment of choice in patients with DKD.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Kidney; Network Meta-Analysis; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 35665989
DOI: 10.1111/dom.14702 -
British Journal of Clinical Pharmacology Aug 2022Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of medications mainly used for the treatment of type 2 diabetes. They improve glucose tolerance,... (Meta-Analysis)
Meta-Analysis Review
AIMS
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of medications mainly used for the treatment of type 2 diabetes. They improve glucose tolerance, increase insulin secretion and induce weight loss. There is controversy about the effect of GLP-1 RAs on serum uric acid (SUA) concentration. Our systematic review aims to objectively answer whether GLP-1 RAs affect SUA levels.
METHODS
We performed a systematic search on PubMed, Web of Science, Embase, Scopus and Google Scholar datasets up to 27August 2021 with a language restriction of English only. Randomized controlled trials, observational studies, uncontrolled trials and conference abstracts were included. Studies with insufficient data, irrelevant types of study and follow-up duration of less than a month were excluded from the review. After critical appraisal by the Joanna Briggs Institute checklists, articles underwent data extraction using a prespecified Microsoft Excel sheet.
RESULTS
Of 1004 identified studies, 17 were eligible for inclusion in this systematic review. Pre- to post-administration analysis of GLP-1 RA effects on SUA demonstrated that GLP-1 RAs could significantly reduce SUA concentration (difference in means -0.341, SE 0.063, P value <0.001). However, when compared to placebo, GLP-1RAs did not perform any better in lowering SUA concentration (difference in means -0.455, SE 0.259, P value 0.079). Surprisingly, the active controls, which included insulin, metformin, sodium-glucose co-transporter 2 (SGLT-2) inhibitors and dipeptidyl-peptidase 4 inhibitors, did outperform GLP-1 RAs in reducing SUA concentration (difference in means 0.250, SE 0.038, P value <0.001).
CONCLUSIONS
Administration of GLP-1 RAs can result in a significant reduction in SUA concentration. However, this reduction is less than that seen with the use of insulin, metformin and SGLT-2 inhibitors.
Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucose; Humans; Hypoglycemic Agents; Insulin; Metformin; Sodium-Glucose Transporter 2 Inhibitors; Uric Acid
PubMed: 35384008
DOI: 10.1111/bcp.15344 -
Osteoporosis International : a Journal... Oct 2019In the present meta-analysis based on real-world data, the use of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1ra), or... (Meta-Analysis)
Meta-Analysis Review
Risk of fracture with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in real-world use: systematic review and meta-analysis of observational studies.
UNLABELLED
In the present meta-analysis based on real-world data, the use of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1ra), or sodium-glucose cotransporter-2 inhibitors (SGLT2i) was not associated with the risk of fracture.
INTRODUCTION
Cumulative evidence from randomized control trials (RCTs) with limited fracture events showed that the use of DPP-4i, GLP-1ra, or SGLT2i may not affect the risk of fracture. However, additional insights from large population-based studies with routinely collected data on fracture events and an adequate amount of fracture events are necessary to draw firm conclusions. To refine and complement the results from RCTs, a systematic review and meta-analysis of observational studies were performed to investigate the association between the use of DPP-4i, GLP-1ra, or SGLT2i and the risk of fracture in real-world settings.
METHODS
The PubMed and Web of Science databases were searched to identify relevant observational studies. A random-effect model was used to estimate the summary relative risks (RRs).
RESULTS
The use of DPP-4i (RR 0.83, 95% CI [confidence interval] 0.60, 1.14; n = 11), GLP-1ra (RR 0.65, 95% CI 0.24, 1.74; n = 4), or SGLT2i (RR 1.02, 95% CI 0.91, 1.16; n = 4) was not associated with the risk of fracture. In general, there was a consistent lack of association between the use of DPP-4i or GLP-1ra and the risk of fracture across nearly all subgroups, except for a significantly reduced risk of hip fracture with the use of GLP-1ra (RR 0.21, 95% CI 0.04, 0.98).
CONCLUSIONS
Cumulative real-world evidence does not support an association between the use of DPP-4i, GLP-1ra, or SGLT2i and the risk of fracture. Our findings, together with the cumulative evidence from RCTs, should reassure policy makers and medical practitioners that the use of these medications is unlikely to increase the risk of fracture among type 2 diabetes mellitus patients in general. Further studies need to investigate the long-term impact of these drugs on the fracture risk, particularly in high-risk populations.
Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Observational Studies as Topic; Osteoporotic Fractures; Risk Assessment; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 31134305
DOI: 10.1007/s00198-019-04968-x -
Diabetes, Obesity & Metabolism Feb 2021To systematically review the effects of pharmacological and lifestyle interventions on body weight as a secondary outcome in people with type 1 diabetes. (Meta-Analysis)
Meta-Analysis
AIM
To systematically review the effects of pharmacological and lifestyle interventions on body weight as a secondary outcome in people with type 1 diabetes.
METHODS
The Ovid Medline, Embase and Cochrane Library databases were searched for relevant pharmacological (glucagon-like peptide-1 [GLP-1] receptor agonist, sodium-glucose co-transporter-2 [SGLT-2] inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor and metformin) and lifestyle intervention studies (diet and exercise) for adults with type 1 diabetes reporting body weight change and HbA1c published from January 2000 to May 2020. Meta-analyses were performed for 16 randomized controlled trials (RCTs).
RESULTS
Thirty-three RCTs (n = 9344 participants), 26 pharmacological (on average 43.9 years, 83.1 kg, HbA1c 8.1%; 55.8% male) and seven lifestyle-based interventions (on average 37.0 years, 85.0 kg, HbA1c 8.1%; 84.6% male), were analysed. The GLP-1 receptor agonist liraglutide 0.6 mg (mean difference [MD]: -2.22 kg [95% CI: -2.55 to -1.90]), 1.2 mg (MD: -3.74 kg [95% CI: -4.16 to -3.33]) and 1.8 mg (MD: -4.85 kg [95% CI: -5.29 to -4.41]), and the SGLT-2 inhibitors empagliflozin 2.5 mg (MD: -1.47 kg [95% CI: -2.23 to -0.71]), 10 mg (MD: -2.77 kg [95% CI: -3.24 to -2.31]) and 25 mg (MD: -3.06 kg [95% CI: -3.57 to -2.55]) and sotagliflozin 200 mg (MD: -2.40 kg [95% CI: -2.87 to -1.94]) and 400 mg (MD: -3.23 [95% CI: -3.73 to -2.72]) were associated with significant reductions in body weight. No significant effect on body weight was found for DPP-4 inhibitors, other GLP-1-receptor agonists, metformin, or for lifestyle interventions (i.e. exercise and diet).
CONCLUSIONS
In people with type 1 diabetes, several adjuvant pharmacological interventions showed weight reduction as a secondary outcome. Future studies in overweight people with type 1 diabetes are needed to establish whether the lifestyle and pharmacological interventions reviewed here have potential as components of complex interventions aimed at body weight reduction as a primary outcome.
Topics: Adult; Body Weight; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Life Style; Male
PubMed: 33026152
DOI: 10.1111/dom.14221